The Central Nervous System

№ 9. Nervous system. Brain.

 

The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. Together with the peripheral nervous system, it has a fundamental role in the control of behavior. The CNS is contained within the dorsal cavity, with the brain within the cranial cavity, and the spinal cord in the spinal cavity. The CNS is covered by the meninges. The brain is also protected by the skull, and the spinal cord is also protected by the vertebrae.

 

The nervous system.

Function

 

Brain Function

 

Since the strong theoretical influence of cybernetics in the fifties, the CNS is conceived as a system devoted to information processing, where an appropriate motor output is computed as a response to a sensory input. Yet, many threads of research suggest that motor activity exists well before the maturation of the sensory systems and then, that the senses only influence behavior without dictating it. This has brought the conception of the CNS as an autonomous system.

 

Development

 

Neural development

In the developing fetus, the CNS originates from the neural plate, a specialised region of the ectoderm, the most external of the three embryonic layers. During embryonic development, the neural plate folds and forms the neural tube. The internal cavity of the neural tube will give rise to the ventricular system. The regions of the neural tube will differentiate progressively into transversal systems. First, the whole neural tube will differentiate into its two major subdivisions: brain (rostral/cephalic) and spinal cord (caudal). Consecutively, the brain will differentiate into prosencephalon and brainstem. Later, the prosencephalon will subdivide into telencephalon and diencephalon, and the brainstem into mesencephalon and rhombencephalon.

 Neural development.

 

Neuroanatomy

The telencephalon gives rise to the striatum (caudate nucleus and putamen), the hippocampus and the neocortex, its cavity becomes the lateral ventricles (first and second ventricles). The diencephalon give rise to the subthalamus, hypothalamus, thalamus and epithalamus, its cavity to the third ventricle. The mesencephalon gives rise to the tectum, pretectum, cerebral peduncle and its cavity develops into the mesencephalic duct or cerebral aqueduct. Finally, the rhombencephalon gives rise to the pons, the cerebellum and the medulla oblongata, its cavity becomes the fourth ventricle.

 

Evolution

The basic pattern of the CNS is highly conserved throughout the different species of vertebrates and during evolution. The major trend that can be observed is towards a progressive telencephalisation: while in the reptilian brain that region is only an appendix to the large olfactory bulb, it represent most of the volume of the mammalian CNS. In the human brain, the telencephalon covers most of the diencephalon and the mesencephalon. Indeed, the allometric study of brain size among different species shows a striking continuity from rats to whales, and allows us to complete the knowledge about the evolution of the CNS obtained through cranial endocasts.

Human brain

 

The human brain controls the central nervous system (CNS), by way of the cranial nerves and spinal cord, the peripheral nervous system (PNS) and regulates virtually all human activity. Involuntary, or “lower,” actions, such as heart rate, respiration, and digestion, are unconsciously governed by the brain, specifically through the autonomic nervous system. Complex, or “higher,” mental activity, such as thought, reason, and abstraction, is consciously controlled.

 

The human brain main areas.

 

Anatomically, the brain can be divided into three parts: the forebrain, midbrain, and hindbrain; the forebrain includes the several lobes of the cerebral cortex that control higher functions, while the mid- and hindbrain are more involved with unconscious, autonomic functions. During encephalization, human brain mass increased beyond that of other species relative to body mass. This process was especially pronounced in the neocortex, a section of the brain involved with language and consciousness. The neocortex accounts for about 76% of the mass of the human brain; with a neocortex much larger than other animals, humans enjoy unique mental capacities despite having a neuroarchitecture similar to that of more primitive species. Basic systems that alert humans to stimuli, sense events in the environment, and maintain homeostasis are similar to those of basic vertebrates. Human consciousness is founded upon the extended capacity of the modereocortex, as well as the greatly developed structures of the brain stem.

 

 

The human brain lobes.

 

The central structures of the brain are the thalamus, hypothalamus, and pituitary gland. The thalamus relays sensory information to the cerebrum; the hypothalamus helps regulate body functions such as thirst and appetite, as well as sleep, aggression, and sexual behavior; and the pituitary gland produces hormones that play a role in growth, development, and various other physiological variables. The pons, medulla, and midbrain are the three structures that compose the brain stem. The ventricles are natural cavities inside the brain filled with cerebrospinal fluid.

 

The brain structures.

Neurophysiology

The human brain is the source of the conscious, cognitive mind. The mind is the set of cognitive processes related to perception, interpretation, imagination, memories, and crucially language (cf. Broca’s area) of which a person may or may not be aware. Beyond cognitive functions, the brain regulates autonomic processes related to essential body functions such as respiration and heartbeat.The brain controls all movement from lifting a pencil to building a superstructure.

Extended neocortical capacity allows humans some control over emotional behavior, but neural pathways between emotive centers of the brain stem and cerebral motor control areas are shorter than those connecting complex cognitive areas in the neocortex with incoming sensory information from the brain stem. Powerful emotional pathways can modulate spontaneous emotive expression regardless of attempts at cerebral self-control. Emotive stability in humans is associated with planning, experience, and an environment that is both stable and stimulating.

The 19th century discovery of the primary motor cortex mapped to correspond with regions of the body led to popular belief that the brain was organized around a homunculus. A distorted figure drawn to represent the body’s motor map in the prefrontal cortex was popularly recognized as the brain’s homunculus, but function of the human brain is far more complex than this simple figure suggests. A similar, “sensory homunculus” can be drawn in the parietal lobe that parallels that in the frontal lobe.

The human brain appears to have no localized center of conscious control. The brain seems to derive consciousness from interaction among numerous systems within the brain. Executive functions rely on cerebral activities, especially those of the frontal lobes, but redundant and complementary processes within the brain result in a diffuse assignment of executive control that can be difficult to attribute to any single locale. Visual perception generally is processed in the occipital lobe, wherease the primary auditory cortex resides in the temporal lobe.

 A sketch of the human brain by artist Priyan Weerappuli superimposed upon the profile of Michelangelo‘s David.

 

Midbrain functions include routing, selecting, mapping, and cataloging information, including information perceived from the environment and information that is remembered and processed throughout the cerebral cortex. Endocrine functions housed in the midbrain play a leading role in modulating arousal of the cortex and of autonomic systems.

Nerves from the brain stem complex where autonomic functions are modulated joierves routing messages to and from the cerebrum in a bundle that passes through the spinal column to related parts of a body. Twelve pairs of cranial nerves, including some that innervate parts of the head, follow pathways from the medulla oblongata outside the spinal cord.

A definite description of the biological basis for consciousness so far eludes the best efforts of the current generation of researchers. But reasonable assumptions based on observable behaviors and on related internal responses have provided the basis for general classification of elements of consciousness and of likely neural regions associated with those elements. Researchers know people lose consciousness and regain it, they have identified partial losses of consciousness associated with particular neuropathologies and they know that certain conscious activities are impossible without particular neural structures.

VIDEO

 

Structure and Physiology of the Nervous System

 

Study of the brain

Grey matter, the thin layer of cells covering the cerebrum, was believed by most scholars to be the primary center of cognitive and conscious processing. White matter, the mass of glial cells that support the cerebral grey matter, was assumed to primarily provide nourishment, physical support, and connective pathways for the more functional cells on the cerebral surface. But research fueled by the interest of Dr. Marian Diamond in the glial structure of Albert Einstein’s brain led to a line of research that offered strong evidence that glial cells serve a computational role beyond merely transmitting processed signals between more functional parts of the brain. In 2004, Scientific American published an article suggesting scientists in the early 21st century are only beginning to study the “other half of the brain.”

For many millennia the function of the brain was unknown. Ancient Egyptians threw the brain away prior to the process of mummification. Ancient thinkers such as Aristotle imagined that mental activity took place in the heart. Greek scholars assumed correctly that the brain serves a role in cooling the body, but incorrectly presumed the brain to function as a sort of radiator, rather than as a thermostat as is now understood. The Alexandrian biologists Herophilos and Erasistratus were among the first to conclude that the brain was the seat of intelligence. Galen’s theory that the brain’s ventricles were the sites of thought and emotion prevailed until the work of the Renaissance anatomist.

 

Vesalius.

The modern study of the brain and its functions is known as neuroscience. Psychology is the scientific study of the mind and behavior. Neurophysiology is the study of normal healthy brain activity, while neurology and psychiatry are both medical approaches to the study of the mind and its disorders and pathology or mental illness respectively.

 

The brain is now thought to be the primary organ responsible for the phenomena of consciousness and thought. It also integrates and controls (together with the central nervous system) allostatic balance and autonomic functions in the body, regulates as well as directly producing many hormones, and performs processing, recognition, cognition and integration related to emotion. Studies of brain damage resulting from accidents led to the identification of specialized areas of the brain devoted to functions such as the processing of vision and audition.

Neuroimaging has allowed the function of the living brain to be studied in detail without damaging the brain. New imaging techniques allowed blood flow within the brain to be studied in detail during a wide range of psychological tests. Functional neuroimaging such as functional magnetic resonance imaging and positron emission tomography allows researchers to monitor activities of the brain as they occur (see also history of neuroimaging).

Molecular analysis of the brain has provided insight into some aspects of what the brain does as an organ, but not how it functions in higher-level processes. Further, the molecular and cell biological examination of brain pathology is hindered by the scarcity of appropriate samples for study, the (usual) inability to biopsy the brain from a living person suffering from a malady, and an incomplete description of the brain’s microanatomy. With respect to the normal brain, comparative transcriptome analysis between the human and chimpanzee brain and between brain and liver (a common molecular baseline organ) has revealed specific and consistent differences in gene expression between human and chimpanzee brain and a general increase in the gene expression of many genes in humans as compared to chimpanzees. Furthermore, variations in gene expression in the cerebral cortex between individuals in either species is greater than between sub-regions of the cortex of a single individual.

In addition to pathological and imaging studies, the study of computational networks, largely in computer science, provided another means through which to understand neural processes. A body of knowledge developed for the production of electronic, mathematical computation of systems provided a basis for researchers to develop and refine hypotheses about the computational function of biological neural networks. The study of neural networks now involves study of both biological and artificial neural networks.

A new discipline of cognitive science has started to fuse the results of these investigations with observations from psychology, philosophy, linguistics, and computer science as expressed in On Intelligence.

Recently the brain was used in bionics by several groups of researchers. In a particular example, a joint team of United States Navy researchers and Russian scientists from Nizhny Novgorod State University worked to develop an artificial analogue of olivocerebellar circuit, a part of the brain responsible for balance and limb movement. The researchers plan to use it to control Autonomous Underwater Vehicles. In human beings, it is the left hemisphere that usually contains the specialized language areas. While this holds true for 97% of right-handed people, about 19% of left-handed people have their language areas in the right hemisphere and as many as 68% of them have some language abilities in both the left and the right hemispheres. Studies of children have provided some fascinating information: If a child has damage to the left hemisphere, the child may develop language in the right hemisphere instead. The younger the child, the better the recovery. So, although the “natural” tendency is for language to develop on the left, our brains are capable of adapting to difficult circumstances, if the damage occurs early enough.

The first language area within the left hemisphere to be discovered is called Broca’s Area, after Paul Broca. The Broca’s area doesn’t just handle getting language out in a motor sense, though. It seems to be more generally involved in the ability to deal with grammar itself, at least the more complex aspects of grammar. For example, it handles distinguishing a sentence in passive form from a simpler subject-verb-object sentence. For instance, the sentence: “The boy was hit by the girl.” implies the girl hit the boy, not the other way around. As a simple subject-verb-object interpretation it could mean: “The boy was hit by the girl.”, and therefore, the boy hit the girl.

The second language area to be discovered is called Wernicke’s Area, after Carl Wernicke, a Germaeurologist. The problem of not understanding the speech of others is known as Wernicke’s Aphasia. Wernicke’s is not just about speech comprehension. People with Wernicke’s Aphasia also have difficulty naming things, often responding with words that sound similar, or the names of related things, as if they are having a very hard time with their mental “dictionaries.”

 

Brain enhancement

Various methods have been proposed to improve the cognitive performance of the human brain including pharmacological methods (nootropic drugs), electric stimulation (direct current polarization) and surgery. More advanced methods of brain enhancement may be possible in the future, perhaps including direct brain-computer interfaces. These proposed enhancements are a major focus of Transhumanism.

 

Comparison of the brain and a computer

Much interest has been focused on comparing the brain with computers. A variety of obvious analogies exist: for example, individual neurons can be compared with a microchip, and the specialised parts of the brain can be compared with graphics cards and other system components. However, such comparisons are fraught with difficulties. Perhaps the most fundamental difference between brains and computers is that today’s computers operate by performing often sequential instructions from an input program, while no clear analogy of a program appears in human brains. The closest equivalent would be the idea of a logical process, but the nature and existence of such entities are subjects of philosophical debate. Given Turing’s model of computation, the Turing machine, this may be a functional, not fundamental, distinction. However, Maass and Markram have recently argued that “in contrast to Turing machines, generic computations by neural circuits are not digital, and are not carried out on static inputs, but rather on functions of time” (the Turing machine computes computable functions). Ultimately, computers were not designed to be models of the brain, though subjects like neural networks attempt to abstract the behavior of the brain in a way that can be simulated computationally.

In addition to the technical differences, other key differences exist. The brain is massively parallel and interwoven, whereas programming of this kind is extremely difficult for computer software writers (most parallel systems run semi-independently, for example each working on a small separate ‘chunk’ of a problem). The human brain is also mediated by chemicals and analog processes, many of which are only understood at a basic level and others of which may not yet have been discovered, so that a full description is not yet available in science. Finally, and perhaps most significantly, the human brain appears hard-wired with certain abilities, such as the ability to learn language (cf. Broca’s area), to interact with experience and unchosen emotions, and usually develops within a culture. This is different from a computer in that a computer needs software to perform many of its functions beyond its basic computational capabilities.

Nevertheless, there have beeumerous attempts to quantify differences in capability between the human brain and computers. According to Hans Moravec, by extrapolating from known capabilities of the retina to process image inputs, a brain has a processing capacity of 100 trillion instructions per second (100 million MIPS), and is likely to be surpassed by computers by 2030.

The computational power of the human brain is difficult to ascertain, as the human brain is not easily paralleled to the binary number processing of today’s computers. For instance, multiplying two large numbers can be accomplished in a fraction of a second with a typical calculator or desktop computer, while the average human may require a pen-and-paper approach to keep track of each stage of the calculation over a period of five or more seconds. Yet, while the human brain is calculating a math problem in an attentive state, it is subconsciously processing data from millions of nerve cells that handle the visual input of the paper and surrounding area, the aural input from both ears, and the sensory input of millions of cells throughout the body. The brain is regulating the heartbeat, monitoring oxygen levels, hunger and thirst requirements, breathing patterns and hundreds of other essential factors throughout the body. It is simultaneously comparing data from the eyes and the sensory cells in the arms and hands to keep track of the position of the pen and paper as the calculation is being performed. It quickly traverses a vast, interconnected network of cells for relevant information on how to solve the problem it is presented, what symbols to write and what their functions are, as it graphs their shape and communicates to the hand how to make accurate and controlled strokes to draw recognizable shapes and numbers onto a page.

The nervous system is the part of an animal’s body that coordinates the actions of the animal and transmits signals between different parts of its body. In most types of animals it consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS contains the brain and spinal cord. The PNS consists mainly of nerves, which are long fibers that connect the CNS to every other part of the body. The PNS includes motor neurons, mediating voluntary movement, the autonomic nervous system, comprising the sympathetic nervous system and the parasympathetic nervous system and regulating involuntary functions, and the enteric nervous system, a semi-independent part of the nervous system whose function is to control the gastrointestinal system.

The central nervous system (CNS) is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except radially symmetric animals such as sponges and jellyfish. It contains the majority of the nervous system and consists of the brain and the spinal cord. Some classifications also include the retina and the cranial nerves in the CNS. Together with the peripheral nervous system, it has a fundamental role in the control of behavior. The CNS is contained within the dorsal cavity, with the brain in the cranial cavity and the spinal cord in the spinal cavity. In vertebrates, the brain is protected by the skull, while the spinal cord is protected by the vertebrae, and both are enclosed in the meninges.

 

Neural development

Neural development refers to the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms. The field draws on both neuroscience and developmental biology to provide insight into the cellular and molecular mechanisms by which complex nervous systems develop. Defects in neural development can lead to cognitive, motor, and intellectual disability, as well as neurological disorders such as autism, Rett syndrome, and mental retardation.

 

Overview of brain development

The nervous system is derived from the ectoderm – the outermost tissue layer – of the embryo. In the third week of development the neuroectoderm appears and forms the neural plate along the dorsal side of the embryo. This neural plate is the source of the majority of neurons and glial cells in the mature human. A groove forms in the neural plate and, by week four of development, the neural plate wraps in on itself to make a hollow neural tube. Because this neural tube later gives rise to the brain and spinal cord any mutations at this stage in development can lead to lethal deformities like anencephaly or lifelong disabilities like spina bifida. The most anterior part of the neural tube is called the telencephalon, which expands rapidly due to cell proliferation, and eventually gives rise to the brain. Gradually some of the cells stop dividing and differentiate into neurons and glial cells, which are the main cellular components of the brain. The newly generated neurons migrate to different parts of the developing brain to self-organize into different brain structures. Once the neurons have reached their regional positions, they extend axons and dendrites, which allow them to communicate with other neurons via synapses. Synaptic communication betweeeurons leads to the establishment of functional neural circuits that mediate sensory and motor processing, and underlie behavior. The human brain does most of its development within the first 20 years of life.

 

Aspects of neural development

Some landmarks of neural development include the birth and differentiation of neurons from stem cell precursors, the migration of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axons and dendrites from neurons, guidance of the motile growth cone through the embryo towards postsynaptic partners, the generation of synapses between these axons and their postsynaptic partners, and finally the lifelong changes in synapses, which are thought to underlie learning and memory.

Typically, these neurodevelopmental processes can be broadly divided into two classes: activity-independent mechanisms and activity-dependent mechanisms. Activity-independent mechanisms are generally believed to occur as hardwired processes determined by genetic programs played out within individual neurons. These include differentiation, migration and axon guidance to their initial target areas. These processes are thought of as being independent of neural activity and sensory experience. Once axons reach their target areas, activity-dependent mechanisms come into play. Although synapse formation is an activity-independent event, modification of synapses and synapse elimination requires neural activity.

Developmental neuroscience uses a variety of animal models including mice Mus musculus, the fruit fly Drosophila melanogaster, the zebrafish Danio rerio, Xenopus laevis tadpoles and the worm Caenorhabditis elegans, among others.

 

Neural induction

During early embryonic development the ectoderm becomes specified to give rise to the epidermis (skin) and the neural plate. The conversion of undifferentiated ectoderm to neuro-ectoderm requires signals from the mesoderm. At the onset of gastrulation presumptive mesodermal cells move through the dorsal blastopore lip and form a layer in between the endoderm and the ectoderm. These mesodermal cells that migrate along the dorsal midline give rise to a structure called the notochord. Ectodermal cells overlying the notochord develop into the neural plate in response to a diffusible signal produced by the notochord. The remainder of the ectoderm gives rise to the epidermis (skin). The ability of the mesoderm to convert the overlying ectoderm into neural tissue is called neural induction.

 

The neural plate folds outwards during the third week of gestation to form the neural groove. Beginning in the future neck region, the neural folds of this groove close to create the neural tube. The formation of the neural tube from the ectoderm is called neurulation. The ventral part of the neural tube is called the basal plate; the dorsal part is called the alar plate. The hollow interior is called the neural canal. By the end of the fourth week of gestation, the open ends of the neural tube, called the neuropores, close off.

 

A transplanted blastopore lip can convert ectoderm into neural tissue and is said to have an inductive effect. Neural inducers are molecules that can induce the expression of neural genes in ectoderm explants without inducing mesodermal genes as well. Neural induction is often studied in xenopus embryos since they have a simple body pattern and there are good markers to distinguish between neural and non-neural tissue. Examples of neural inducers are the molecules noggin and chordin.

 

When embryonic ectodermal cells are cultured at low density in the absence of mesodermal cells they undergo neural differentiation (express neural genes), suggesting that neural differentiation is the default fate of ectodermal cells. In explant cultures (which allow direct cell-cell interactions) the same cells differentiate into epidermis. This is due to the action of BMP4 (a TGF-β family protein) that induces ectodermal cultures to differentiate into epidermis. During neural induction, noggin and chordin are produced by the dorsal mesoderm (notochord) and diffuse into the overlying ectoderm to inhibit the activity of BMP4. This inhibition of BMP4 causes the cells to differentiate into neural cells. Inhibition of TGF-β and BMP signaling can efficiently induce neural tissue from human pluripotent stem cells, a model of early human development.

 

Regionalization

Late in the fourth week, the superior part of the neural tube flexes at the level of the future midbrain—the mesencephalon. Above the mesencephalon is the prosencephalon (future forebrain) and beneath it is the rhombencephalon (future hindbrain).

 

The optical vesicle (which eventually become the optic nerve, retina and iris) forms at the basal plate of the prosencephalon. The alar plate of the prosencephalon expands to form the cerebral hemispheres (the telencephalon) whilst its basal plate becomes the diencephalon. Finally, the optic vesicle grows to form an optic outgrowth.

 

Patterning of the nervous system

In chordates, dorsal ectoderm forms all neural tissue and the nervous system. Patterning occurs due to specific environmental conditions – different concentrations of signaling molecules

 

Dorsoventral axis

The ventral half of the neural plate is controlled by the notochord, which acts as the ‘organiser’. The dorsal half is controlled by the ectoderm plate, which flanks either side of the neural plate.

 

Ectoderm follows a default pathway to become neural tissue. Evidence for this comes from single, cultured cells of ectoderm, which go on to form neural tissue. This is postulated to be because of a lack of BMPs, which are blocked by the organiser. The organiser may produce molecules such as follistatin, noggin and chordin that inhibit BMPs.

 

The ventral neural tube is patterned by Sonic Hedgehog (Shh) from the notochord, which acts as the inducing tissue. Notochord-derived Shh signals to the floor plate, and induces Shh expression in the floor plate. Floor plate-derived Shh subsequently signals to other cells in the neural tube, and is essential for proper specification of ventral neuron progenitor domains. Loss of Shh from the notochord and/or floor plate prevents proper specification of these progenitor domains. Shh binds Patched1, relieving Patched-mediated inhibition of Smoothened, leading to activation of Gli family of transcription factors (Gli1, Gli2, and Gli3) transcription factors.

 

In this context Shh acts as a morphogen – it induces cell differentiation dependent on its concentration. At low concentrations it forms ventral interneurones, at higher concentrations it induces motor neuron development, and at highest concentrations it induces floor plate differentiation. Failure of Shh-modulated differentiation causes holoprosencephaly.

 

The dorsal neural tube is patterned by BMPs from the epidermal ectoderm flanking the neural plate. These induce sensory interneurones by activating Sr/Thr kinases and altering SMAD transcription factor levels.

 

Rostrocaudal (Anteroposterior) axis

Signals that control anteroposterior neural development include FGF and retinoic acid, which act in the hindbrain and spinal cord.[6] The hindbrain, for example, is patterned by Hox genes, which are expressed in overlapping domains along the anteroposterior axis under the control of retinoic acid. The 3′ genes in the Hox cluster are induced by retinoic acid in the hindbrain, whereas the 5′ Hox genes are not induced by retinoic acid and are expressed more posteriorly in the spinal cord. Hoxb-1 is expressed in rhombomere 4 and gives rise to the facial nerve. Without this Hoxb-1 expression, a nerve similar to the trigeminal nerve arises.

Neuronal migration

Corticogenesis: younger neurons migrate past older ones using radial glia as a scaffolding. Cajal-Retzius cells (red) release reelin (orange).

 

Neuronal migration is the method by which neurons travel from their origin or birthplace to their final position in the brain. There are several ways they can do this, e.g. by radial migration or tangential migration. This time lapse displays sequences of radial migration (also known as glial guidance) and somal translocation.

 

Tangential migration of interneurons from ganglionic eminence. Radial migration Neuronal precursor cells proliferate in the ventricular zone of the developing neocortex. The first postmitotic cells to migrate form the preplate, which are destined to become Cajal-Retzius cells and subplate neurons. These cells do so by somal translocation. Neurons migrating with this mode of locomotion are bipolar and attach the leading edge of the process to the pia. The soma is then transported to the pial surface by nucleokinesis, a process by which a microtubule “cage” around the nucleus elongates and contracts in association with the centrosome to guide the nucleus to its final destination. Radial glia, whose fibers serve as a scaffolding for migrating cells, can itself divide or translocate to the cortical plate and differentiate either into astrocytes or neurons. Somal translocation can occur at any time during development.

 

Subsequent waves of neurons split the preplate by migrating along radial glial fibres to form the cortical plate. Each wave of migrating cells travel past their predecessors forming layers in an inside-out manner, meaning that the youngest neurons are the closest to the surface. It is estimated that glial guided migration represents 90% of migrating neurons in human and about 75% in rodents.

 

Tangential migration Most interneurons migrate tangentially through multiple modes of migration to reach their appropriate location in the cortex. An example of tangential migration is the movement of interneurons from the ganglionic eminence to the cerebral cortex. One example of ongoing tangential migration in a mature organism, observed in some animals, is the rostral migratory stream connecting subventricular zone and olfactory bulb.

 

Others modes of migration There is also a method of neuronal migration called multipolar migration. This is seen in multipolar cells, which are abundantly present in the cortical intermediate zone. They do not resemble the cells migrating by locomotion or somal translocation. Instead these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers.

Neurotrophic factors

The survival of neurons is regulated by survival factors, called trophic factors. The neurotrophic hypothesis was formulated by Victor Hamburger and Rita Levi Montalcini based on studies of the developing nervous system. Victor Hamburger discovered that implanting an extra limb in the developing chick led to an increase in the number of spinal motor neurons. Initially he thought that the extra limb was inducing proliferation of motor neurons, but he and his colleagues later showed that there was a great deal of motor neuron death during normal development, and the extra limb prevented this cell death. According to the neurotrophic hypothesis, growing axons compete for limiting amounts of target-derived trophic factors and axons that neurons that fail to receive sufficient trophic support die by apoptosis. It is now clear that factors produced by a number of sources contribute to neuronal survival.

Nerve Growth Factor (NGF): Rita Levi Montalcini and Stanley Cohen purified the first trophic factor, Nerve Growth Factor (NGF), for which they received the Nobel Prize. There are three NGF-related trophic factors: BDNF, NT3, and NT4, which regulate survival of various neuronal populations. The Trk proteins act as receptors for NGF and related factors. Trk is a receptor tyrosine kinase. Trk dimerization and phosphorylation leads to activation of various intracellular signaling pathways including the MAP kinase, Akt, and PKC pathways.

CNTF: Ciliary neurotrophic factor is another protein that acts as a survival factor for motor neurons. CNTF acts via a receptor complex that includes CNTFRα, GP130, and LIFRβ. Activation of the receptor leads to phosphorylation and recruitment of the JAK kinase, which in turn phosphorylates LIFRβ. LIFRβ acts as a docking site for the STAT transcription factors. JAK kinase phosphorylates STAT proteins, which dissociate from the receptor and translocate to the nucleus to regulate gene expression.

GDNF: Glial derived neurotrophic factor is a member of the TGFb family of proteins, and is a potent trophic factor for striatal neurons. The functional receptor is a heterodimer, composed of type 1 and type 2 receptors. Activation of the type 1 receptor leads to phosphorylation of Smad proteins, which translocate to the nucleus to activate gene expression.

 

Synapse formation

Neuromuscular junction Much of our understanding of synapse formation comes from studies at the neuromuscular junction. The transmitter at this synapse is acetylcholine. The acetylcholine receptor (AchR) is present at the surface of muscle cells before synapse formation. The arrival of the nerve induces clustering of the receptors at the synapse. McMahan and Sanes showed that the synaptogenic signal is concentrated at the basal lamina. They also showed that the synaptogenic signal is produced by the nerve, and they identified the factor as Agrin. Agrin induces clustering of AchRs on the muscle surface and synapse formation is disrupted in agrin knockout mice. Agrin transduces the signal via MuSK receptor to rapsyn. Fischbach and colleagues showed that receptor subunits are selectively transcribed from nuclei next to the synaptic site. This is mediated by neuregulins.

 

In the mature synapse each muscle fiber is innervated by one motor neuron. However, during development many of the fibers are innervated by multiple axons. Lichtman and colleagues have studied the process of synapses elimination. This is an activity-dependent event. Partial blockage of the receptor leads to retraction of corresponding presynaptic terminals.

 

CNS synapses Agrin appears not to be a central mediator of CNS synapse formation and there is active interest in identifying signals that mediate CNS synaptogenesis. Neurons in culture develop synapses that are similar to those that form in vivo, suggesting that synaptogenic signals can function properly in vitro. CNS synaptogenesis studies have focused mainly on glutamatergic synapses. Imaging experiments show that dendrites are highly dynamic during development and often initiate contact with axons. This is followed by recruitment of postsynaptic proteins to the site of contact. Stephen Smith and colleagues have shown that contact initiated by dendritic filopodia can develop into synapses.

 

Induction of synapse formation by glial factors: Barres and colleagues made the observation that factors in glial conditioned media induce synapse formation in retinal ganglion cell cultures. Synapse formation in the CNS is correlated with astrocyte differentiation suggesting that astrocytes might provide a synaptogenic factor. The identity of the astrocytic factors is not yet known.

 

Neuroligins and SynCAM as synaptogenic signals: Sudhof, Serafini, Scheiffele and colleagues have shown that neuroligins and SynCAM can act as factors that induce presynaptic differentiation. Neuroligins are concentrated at the postsynaptic site and act via neurexins concentrated in the presynaptic axons. SynCAM is a cell adhesion molecule that is present in both pre- and post-synaptic membranes.

 

Synapse elimination

Several motorneurones compete for each neuromuscular junction, but only one survives until adulthood. Competition in vitro has been shown to involve a limited neurotrophic substance that is released, or that neural activity infers advantage to strong post-synaptic connections by giving resistance to a toxin also released upoerve stimulation. In vivo it is suggested that muscle fibres select the strongest neuron through a retrograde signal.

Tangential migration of interneurons from ganglionic eminence.

 

Radial migration Neuronal precursor cells proliferate in the ventricular zone of the developing neocortex. The first postmitotic cells to migrate form the preplate, which are destined to become Cajal-Retzius cells and subplate neurons. These cells do so by somal translocation. Neurons migrating with this mode of locomotion are bipolar and attach the leading edge of the process to the pia. The soma is then transported to the pial surface by nucleokinesis, a process by which a microtubule “cage” around the nucleus elongates and contracts in association with the centrosome to guide the nucleus to its final destination. Radial glia, whose fibers serve as a scaffolding for migrating cells, can itself divide or translocate to the cortical plate and differentiate either into astrocytes or neurons. Somal translocation can occur at any time during development.

 

Subsequent waves of neurons split the preplate by migrating along radial glial fibres to form the cortical plate. Each wave of migrating cells travel past their predecessors forming layers in an inside-out manner, meaning that the youngest neurons are the closest to the surface. It is estimated that glial guided migration represents 90% of migrating neurons in human and about 75% in rodents.

Tangential migration Most interneurons migrate tangentially through multiple modes of migration to reach their appropriate location in the cortex. An example of tangential migration is the movement of interneurons from the ganglionic eminence to the cerebral cortex. One example of ongoing tangential migration in a mature organism, observed in some animals, is the rostral migratory stream connecting subventricular zone and olfactory bulb.

 

Others modes of migration There is also a method of neuronal migration called multipolar migration. This is seen in multipolar cells, which are abundantly present in the cortical intermediate zone. They do not resemble the cells migrating by locomotion or somal translocation. Instead these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers.

 

Neurotrophic factors

The survival of neurons is regulated by survival factors, called trophic factors. The neurotrophic hypothesis was formulated by Victor Hamburger and Rita Levi Montalcini based on studies of the developing nervous system. Victor Hamburger discovered that implanting an extra limb in the developing chick led to an increase in the number of spinal motor neurons. Initially he thought that the extra limb was inducing proliferation of motor neurons, but he and his colleagues later showed that there was a great deal of motor neuron death during normal development, and the extra limb prevented this cell death. According to the neurotrophic hypothesis, growing axons compete for limiting amounts of target-derived trophic factors and axons that neurons that fail to receive sufficient trophic support die by apoptosis. It is now clear that factors produced by a number of sources contribute to neuronal survival.

Nerve Growth Factor (NGF): Rita Levi Montalcini and Stanley Cohen purified the first trophic factor, Nerve Growth Factor (NGF), for which they received the Nobel Prize. There are three NGF-related trophic factors: BDNF, NT3, and NT4, which regulate survival of various neuronal populations. The Trk proteins act as receptors for NGF and related factors. Trk is a receptor tyrosine kinase. Trk dimerization and phosphorylation leads to activation of various intracellular signaling pathways including the MAP kinase, Akt, and PKC pathways.

CNTF: Ciliary neurotrophic factor is another protein that acts as a survival factor for motor neurons. CNTF acts via a receptor complex that includes CNTFRα, GP130, and LIFRβ. Activation of the receptor leads to phosphorylation and recruitment of the JAK kinase, which in turn phosphorylates LIFRβ. LIFRβ acts as a docking site for the STAT transcription factors. JAK kinase phosphorylates STAT proteins, which dissociate from the receptor and translocate to the nucleus to regulate gene expression.

GDNF: Glial derived neurotrophic factor is a member of the TGFb family of proteins, and is a potent trophic factor for striatal neurons. The functional receptor is a heterodimer, composed of type 1 and type 2 receptors. Activation of the type 1 receptor leads to phosphorylation of Smad proteins, which translocate to the nucleus to activate gene expression.

 

Synapse formation

Neuromuscular junction Much of our understanding of synapse formation comes from studies at the neuromuscular junction. The transmitter at this synapse is acetylcholine. The acetylcholine receptor (AchR) is present at the surface of muscle cells before synapse formation. The arrival of the nerve induces clustering of the receptors at the synapse. McMahan and Sanes showed that the synaptogenic signal is concentrated at the basal lamina. They also showed that the synaptogenic signal is produced by the nerve, and they identified the factor as Agrin. Agrin induces clustering of AchRs on the muscle surface and synapse formation is disrupted in agrin knockout mice. Agrin transduces the signal via MuSK receptor to rapsyn. Fischbach and colleagues showed that receptor subunits are selectively transcribed from nuclei next to the synaptic site. This is mediated by neuregulins.

 

In the mature synapse each muscle fiber is innervated by one motor neuron. However, during development many of the fibers are innervated by multiple axons. Lichtman and colleagues have studied the process of synapses elimination. This is an activity-dependent event. Partial blockage of the receptor leads to retraction of corresponding presynaptic terminals.

 

CNS synapses Agrin appears not to be a central mediator of CNS synapse formation and there is active interest in identifying signals that mediate CNS synaptogenesis. Neurons in culture develop synapses that are similar to those that form in vivo, suggesting that synaptogenic signals can function properly in vitro. CNS synaptogenesis studies have focused mainly on glutamatergic synapses. Imaging experiments show that dendrites are highly dynamic during development and often initiate contact with axons. This is followed by recruitment of postsynaptic proteins to the site of contact. Stephen Smith and colleagues have shown that contact initiated by dendritic filopodia can develop into synapses.

 

Induction of synapse formation by glial factors: Barres and colleagues made the observation that factors in glial conditioned media induce synapse formation in retinal ganglion cell cultures. Synapse formation in the CNS is correlated with astrocyte differentiation suggesting that astrocytes might provide a synaptogenic factor. The identity of the astrocytic factors is not yet known.

 

Neuroligins and SynCAM as synaptogenic signals: Sudhof, Serafini, Scheiffele and colleagues have shown that neuroligins and SynCAM can act as factors that induce presynaptic differentiation. Neuroligins are concentrated at the postsynaptic site and act via neurexins concentrated in the presynaptic axons. SynCAM is a cell adhesion molecule that is present in both pre- and post-synaptic membranes.

 

Synapse elimination

Several motorneurones compete for each neuromuscular junction, but only one survives until adulthood. Competition in vitro has been shown to involve a limited neurotrophic substance that is released, or that neural activity infers advantage to strong post-synaptic connections by giving resistance to a toxin also released upoerve stimulation. In vivo it is suggested that muscle fibres select the strongest neuron through a retrograde signal.

At the cellular level, the nervous system is defined by the presence of a special type of cell, called the neuron, also known as a “nerve cell”. Neurons have special structures that allow them to send signals rapidly and precisely to other cells. They send these signals in the form of electrochemical waves traveling along thin fibers called axons, which cause chemicals called neurotransmitters to be released at junctions called synapses. A cell that receives a synaptic signal from a neuron may be excited, inhibited, or otherwise modulated. The connections betweeeurons form neural circuits that generate an organism’s perception of the world and determine its behavior. Along with neurons, the nervous system contains other specialized cells called glial cells (or simply glia), which provide structural and metabolic support.

The peripheral nervous system (PNS, or occasionally PeNS) consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system (CNS) to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain barrier, leaving it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system; some textbooks also include sensory systems. It is also a part of the nervous system.

 

The cranial nerves are part of the PNS with the exception of cranial nerve II, the optic nerve, along with the retina. The second cranial nerve is not a true peripheral nerve but a tract of the diencephalon. Cranial nerve ganglia originate in the CNS. However, the remaining eleven cranial nerve axons extend beyond the brain and are therefore considered part of the PNS.

 

Specific nerves and plexi

Ten out of the twelve cranial nerves originate from the brainstem, and mainly control the functions of the anatomic structures of the head with some exceptions. The nuclei of cranial nerves I and II lie in the forebrain and thalamus, respectively, and are thus not considered to be true cranial nerves. CN X (10) receives visceral sensory information from the thorax and abdomen, and CN XI (11) is responsible for innervating the sternocleidomastoid and trapezius muscles, neither of which is exclusively in the head.

 

Spinal nerves take their origins from the spinal cord. They control the functions of the rest of the body. In humans, there are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal. In the cervical region, the spinal nerve roots come out above the corresponding vertebrae (i.e. nerve root between the skull and 1st cervical vertebrae is called spinal nerve C1). From the thoracic region to the coccygeal region, the spinal nerve roots come out below the corresponding vertebrae. It is important to note that this method creates a problem wheaming the spinal nerve root between C7 and T1 (so it is called spinal nerve root C8). In the lumbar and sacral region, the spinal nerve roots travel within the dural sac and they travel below the level of L2 as the cauda equina.

 

Cervical spinal nerves (C1–C4)

The cervical plexus is a plexus of the ventral rami of the first four cervical spinal nerves which are located from C1 to C4 cervical segment in the neck. They are located laterally to the transverse processes between prevertebral muscles from the medial side and vertebral (m.scalenus, m.levator scapulae, m.splenius cervicis) from lateral side. There is anastomosis with accessory nerve, hypoglossal nerve and sympathetic trunk.

It is located in the neck, deep to sternocleidomastoid. Nerves formed from the cervical plexus innervate the back of the head, as well as some neck muscles. The branches of the cervical plexus emerge from the posterior triangle at the nerve point, a point which lies midway on the posterior border of the Sternocleidomastoid.

 

The first 4 cervical spinal nerves, C1 through C4, split and recombine to produce a variety of nerves that subserve the neck and back of head.

 

Spinal nerve C1 is called the suboccipital nerve which provides motor innervation to muscles at the base of the skull. C2 and C3 form many of the nerves of the neck, providing both sensory and motor control. These include the greater occipital nerve which provides sensation to the back of the head, the lesser occipital nerve which provides sensation to the area behind the ears, the greater auricular nerve and the lesser auricular nerve. See occipital neuralgia. The phrenic nerve arises from nerve roots C3, C4 and C5. It innervates the diaphragm, enabling breathing. If the spinal cord is transected above C3, then spontaneous breathing is not possible. See myelopathy

 

Brachial plexus (C5–T1)

The last four cervical spinal nerves, C5 through C8, and the first thoracic spinal nerve, T1,combine to form the brachial plexus, or plexus brachialis, a tangled array of nerves, splitting, combining and recombining, to form the nerves that subserve the upper-limb and upper back. Although the brachial plexus may appear tangled, it is highly organized and predictable, with little variation between people. See brachial plexus injuries.

 

Lumbosacral plexus (L1–S4)

 

The anterior divisions of the lumbar nerves, sacral nerves, and coccygeal nerve form the lumbosacral plexus, the first lumbar nerve being frequently joined by a branch from the twelfth thoracic. For descriptive purposes this plexus is usually divided into three parts:

lumbar plexus, sacral plexus, and pudendal plexus.

 

Neurotransmitters

The maieurotransmitters of the peripheral nervous system are acetylcholine and noradrenaline. However, there are several other neurotransmitters as well, jointly labeled Non-noradrenergic, non-cholinergic (NANC) transmitters. Examples of such transmitters include non-peptides: ATP, GABA, dopamine, NO, and peptides: neuropeptide Y, VIP, GnRH, Substance P and CGRP.

Nervous systems are found in most multicellular animals, but vary greatly in complexity. The only multicellular animals that have no nervous system at all are sponges, placozoans and mesozoans, which have very simple body plans. The nervous systems of ctenophores (comb jellies) and cnidarians (e.g., anemones, hydras, corals and jellyfishes) consist of a diffuse nerve net. All other types of animals, with the exception of a few types of worms, have a nervous system containing a brain, a central cord (or two cords running in parallel), and nerves radiating from the brain and central cord. The size of the nervous system ranges from a few hundred cells in the simplest worms, to on the order of 100 billion cells in humans.

 

At the most basic level, the function of the nervous system is to send signals from one cell to others, or from one part of the body to others. The nervous system is susceptible to malfunction in a wide variety of ways, as a result of genetic defects, physical damage due to trauma or poison, infection, or simply aging. The medical specialty of neurology studies the causes of nervous system malfunction, and looks for interventions that can prevent it or treat it. In the peripheral nervous system, the most commonly occurring type of problem is failure of nerve conduction, which can have a variety of causes including diabetic neuropathy and demyelinating disorders such as multiple sclerosis and amyotrophic lateral sclerosis.

 

Neuroscience is the field of science that focuses on the study of the nervous system.

 

Structure

The nervous system derives its name from nerves, which are cylindrical bundles of fibers that emanate from the brain and central cord, and branch repeatedly to innervate every part of the body. Nerves are large enough to have been recognized by the ancient Egyptians, Greeks, and Romans, but their internal structure was not understood until it became possible to examine them using a microscope. A microscopic examination shows that nerves consist primarily of the axons of neurons, along with a variety of membranes that wrap around them and segregate them into fascicles. The neurons that give rise to nerves do not lie entirely within the nerves themselves—their cell bodies reside within the brain, central cord, or peripheral ganglia.

 

All animals more advanced than sponges have nervous systems. However, even sponges, unicellular animals, and non-animals such as slime molds have cell-to-cell signalling mechanisms that are precursors to those of neurons. In radially symmetric animals such as the jellyfish and hydra, the nervous system consists of a diffuse network of isolated cells. In bilaterian animals, which make up the great majority of existing species, the nervous system has a common structure that originated early in the Cambrian period, over 500 million years ago.

 

Cells

The nervous system contains two main categories or types of cells: neurons and glial cells.

 

Neurons

The nervous system is defined by the presence of a special type of cell—the neuron (sometimes called “neurone” or “nerve cell”). Neurons can be distinguished from other cells in a number of ways, but their most fundamental property is that they communicate with other cells via synapses, which are membrane-to-membrane junctions containing molecular machinery that allows rapid transmission of signals, either electrical or chemical. Many types of neuron possess an axon, a protoplasmic protrusion that can extend to distant parts of the body and make thousands of synaptic contacts. Axons frequently travel through the body in bundles called nerves.

 

Even in the nervous system of a single species such as humans, hundreds of different types of neurons exist, with a wide variety of morphologies and functions. These include sensory neurons that transmute physical stimuli such as light and sound into neural signals, and motor neurons that transmute neural signals into activation of muscles or glands; however in many species the great majority of neurons receive all of their input from other neurons and send their output to other neurons.

 

Glial cells

Glial cells (named from the Greek for “glue”) are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas. Among the most important functions of glial cells are to support neurons and hold them in place; to supply nutrients to neurons; to insulate neurons electrically; to destroy pathogens and remove dead neurons; and to provide guidance cues directing the axons of neurons to their targets. A very important type of glial cell (oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system) generates layers of a fatty substance called myelin that wraps around axons and provides electrical insulation which allows them to transmit action potentials much more rapidly and efficiently.

 

Anatomy in vertebrates

The nervous system of vertebrate animals (including humans) is divided into the central nervous system (CNS) and peripheral nervous system (PNS).

 

The central nervous system (CNS) is the largest part, and includes the brain and spinal cord. The spinal cavity contains the spinal cord, while the head contains the brain. The CNS is enclosed and protected by meninges, a three-layered system of membranes, including a tough, leathery outer layer called the dura mater. The brain is also protected by the skull, and the spinal cord by the vertebrae.

 

The peripheral nervous system (PNS) is a collective term for the nervous system structures that do not lie within the CNS. The large majority of the axon bundles called nerves are considered to belong to the PNS, even when the cell bodies of the neurons to which they belong reside within the brain or spinal cord. The PNS is divided into somatic and visceral parts. The somatic part consists of the nerves that innervate the skin, joints, and muscles. The cell bodies of somatic sensory neurons lie in dorsal root ganglia of the spinal cord. The visceral part, also known as the autonomic nervous system, contains neurons that innervate the internal organs, blood vessels, and glands. The autonomic nervous system itself consists of two parts: the sympathetic nervous system and the parasympathetic nervous system. Some authors also include sensory neurons whose cell bodies lie in the periphery (for senses such as hearing) as part of the PNS; others, however, omit them.

 

Diagram showing the major divisions of the vertebrate nervous system.

 

The vertebrate nervous system can also be divided into areas called grey matter (“gray matter” in American spelling) and white matter. Grey matter (which is only grey in preserved tissue, and is better described as pink or light brown in living tissue) contains a high proportion of cell bodies of neurons. White matter is composed mainly of myelinated axons, and takes its color from the myelin. White matter includes all of the nerves, and much of the interior of the brain and spinal cord. Grey matter is found in clusters of neurons in the brain and spinal cord, and in cortical layers that line their surfaces. There is an anatomical convention that a cluster of neurons in the brain or spinal cord is called a nucleus, whereas a cluster of neurons in the periphery is called a ganglion. There are, however, a few exceptions to this rule, notably including the part of the forebrain called the basal ganglia.

Comparative anatomy and evolution

Neural precursors in sponges

 

Sponges have no cells connected to each other by synaptic junctions, that is, no neurons, and therefore no nervous system. They do, however, have homologs of many genes that play key roles in synaptic function. Recent studies have shown that sponge cells express a group of proteins that cluster together to form a structure resembling a postsynaptic density (the signal-receiving part of a synapse). However, the function of this structure is currently unclear. Although sponge cells do not show synaptic transmission, they do communicate with each other via calcium waves and other impulses, which mediate some simple actions such as whole-body contraction.

 

Radiata

Jellyfish, comb jellies, and related animals have diffuse nerve nets rather than a central nervous system. In most jellyfish the nerve net is spread more or less evenly across the body; in comb jellies it is concentrated near the mouth. The nerve nets consist of sensory neurons that pick up chemical, tactile, and visual signals, motor neurons that can activate contractions of the body wall, and intermediate neurons that detect patterns of activity in the sensory neurons and send signals to groups of motor neurons as a result. In some cases groups of intermediate neurons are clustered into discrete ganglia.

 

The development of the nervous system in radiata is relatively unstructured. Unlike bilaterians, radiata only have two primordial cell layers, endoderm and ectoderm. Neurons are generated from a special set of ectodermal precursor cells, which also serve as precursors for every other ectodermal cell type.

 

Bilateria

The vast majority of existing animals are bilaterians, meaning animals with left and right sides that are approximate mirror images of each other. All bilateria are thought to have descended from a common wormlike ancestor that appeared in the Cambrian period, 550–600 million years ago. The fundamental bilaterian body form is a tube with a hollow gut cavity running from mouth to anus, and a nerve cord with an enlargement (a “ganglion”) for each body segment, with an especially large ganglion at the front, called the “brain”.

Nervous system of a bilaterian animal, in the form of a nerve cord with segmental enlargements, and a “brain” at the front.

 

Worms

Worms are the simplest bilaterian animals, and reveal the basic structure of the bilaterian nervous system in the most straightforward way. As an example, earthworms have dual nerve cords running along the length of the body and merging at the tail and the mouth. These nerve cords are connected by transverse nerves like the rungs of a ladder. These transverse nerves help coordinate the two sides of the animal. Two ganglia at the head end function similar to a simple brain. Photoreceptors on the animal’s eyespots provide sensory information on light and dark.

 

The nervous system of one very small worm, the roundworm Caenorhabditis elegans, has been mapped out down to the synaptic level. Every neuron and its cellular lineage has been recorded and most, if not all, of the neural connections are known. In this species, the nervous system is sexually dimorphic; the nervous systems of the two sexes, males and hermaphrodites, have different numbers of neurons and groups of neurons that perform sex-specific functions. In C. elegans, males have exactly 383 neurons, while hermaphrodites have exactly 302 neurons.

Earthworm nervous system. Top: side view of the front of the worm. Bottom: nervous system in isolation, viewed from above.

 

Arthropods

Internal anatomy of a spider, showing the nervous system in blue.

 

Arthropods, such as insects and crustaceans, have a nervous system made up of a series of ganglia, connected by a ventral nerve cord made up of two parallel connectives running along the length of the belly. Typically, each body segment has one ganglion on each side, though some ganglia are fused to form the brain and other large ganglia. The head segment contains the brain, also known as the supraesophageal ganglion. In the insect nervous system, the brain is anatomically divided into the protocerebrum, deutocerebrum, and tritocerebrum. Immediately behind the brain is the subesophageal ganglion, which is composed of three pairs of fused ganglia. It controls the mouthparts, the salivary glands and certain muscles. Many arthropods have well-developed sensory organs, including compound eyes for vision and antennae for olfaction and pheromone sensation. The sensory information from these organs is processed by the brain.

 

In insects, many neurons have cell bodies that are positioned at the edge of the brain and are electrically passive—the cell bodies serve only to provide metabolic support and do not participate in signalling. A protoplasmic fiber runs from the cell body and branches profusely, with some parts transmitting signals and other parts receiving signals. Thus, most parts of the insect brain have passive cell bodies arranged around the periphery, while the neural signal processing takes place in a tangle of protoplasmic fibers called neuropil, in the interior.

 

“Identified” neurons

A neuron is called identified if it has properties that distinguish it from every other neuron in the same animal—properties such as location, neurotransmitter, gene expression pattern, and connectivity—and if every individual organism belonging to the same species has one and only one neuron with the same set of properties. In vertebrate nervous systems very few neurons are “identified” in this sense—in humans, there are believed to be none—but in simpler nervous systems, some or all neurons may be thus unique. In the roundworm C. elegans, whose nervous system is the most thoroughly described of any animal’s, every neuron in the body is uniquely identifiable, with the same location and the same connections in every individual worm. One notable consequence of this fact is that the form of the C. elegans nervous system is completely specified by the genome, with no experience-dependent plasticity.

 

The brains of many molluscs and insects also contain substantial numbers of identified neurons. In vertebrates, the best known identified neurons are the gigantic Mauthner cells of fish. Every fish has two Mauthner cells, located in the bottom part of the brainstem, one on the left side and one on the right. Each Mauthner cell has an axon that crosses over, innervating neurons at the same brain level and then travelling down through the spinal cord, making numerous connections as it goes. The synapses generated by a Mauthner cell are so powerful that a single action potential gives rise to a major behavioral response: within milliseconds the fish curves its body into a C-shape, then straightens, thereby propelling itself rapidly forward. Functionally this is a fast escape response, triggered most easily by a strong sound wave or pressure wave impinging on the lateral line organ of the fish. Mauthner cells are not the only identified neurons in fish—there are about 20 more types, including pairs of “Mauthner cell analogs” in each spinal segmental nucleus. Although a Mauthner cell is capable of bringing about an escape response individually, in the context of ordinary behavior other types of cells usually contribute to shaping the amplitude and direction of the response.

 

Mauthner cells have been described as command neurons. A command neuron is a special type of identified neuron, defined as a neuron that is capable of driving a specific behavior individually. Such neurons appear most commonly in the fast escape systems of various species—the squid giant axon and squid giant synapse, used for pioneering experiments ieurophysiology because of their enormous size, both participate in the fast escape circuit of the squid. The concept of a command neuron has, however, become controversial, because of studies showing that some neurons that initially appeared to fit the description were really only capable of evoking a response in a limited set of circumstances.

 

Function

At the most basic level, the function of the nervous system is to send signals from one cell to others, or from one part of the body to others. There are multiple ways that a cell can send signals to other cells. One is by releasing chemicals called hormones into the internal circulation, so that they can diffuse to distant sites. In contrast to this “broadcast” mode of signaling, the nervous system provides “point-to-point” signals—neurons project their axons to specific target areas and make synaptic connections with specific target cells. Thus, neural signaling is capable of a much higher level of specificity than hormonal signaling. It is also much faster: the fastest nerve signals travel at speeds that exceed 100 meters per second.

 

At a more integrative level, the primary function of the nervous system is to control the body. It does this by extracting information from the environment using sensory receptors, sending signals that encode this information into the central nervous system, processing the information to determine an appropriate response, and sending output signals to muscles or glands to activate the response. The evolution of a complex nervous system has made it possible for various animal species to have advanced perception abilities such as vision, complex social interactions, rapid coordination of organ systems, and integrated processing of concurrent signals. In humans, the sophistication of the nervous system makes it possible to have language, abstract representation of concepts, transmission of culture, and many other features of human society that would not exist without the human brain.

Neurons and synapses

Major elements in synaptic transmission. An electrochemical wave called an action potential travels along the axon of a neuron. When the wave reaches a synapse, it provokes release of a small amount of neurotransmitter molecules, which bind to chemical receptor molecules located in the membrane of the target cell.

 

Most neurons send signals via their axons, although some types are capable of dendrite-to-dendrite communication. (In fact, the types of neurons called amacrine cells have no axons, and communicate only via their dendrites.) Neural signals propagate along an axon in the form of electrochemical waves called action potentials, which produce cell-to-cell signals at points where axon terminals make synaptic contact with other cells.

 

Synapses may be electrical or chemical. Electrical synapses make direct electrical connections betweeeurons, but chemical synapses are much more common, and much more diverse in function. At a chemical synapse, the cell that sends signals is called presynaptic, and the cell that receives signals is called postsynaptic. Both the presynaptic and postsynaptic areas are full of molecular machinery that carries out the signalling process. The presynaptic area contains large numbers of tiny spherical vessels called synaptic vesicles, packed with neurotransmitter chemicals. When the presynaptic terminal is electrically stimulated, an array of molecules embedded in the membrane are activated, and cause the contents of the vesicles to be released into the narrow space between the presynaptic and postsynaptic membranes, called the synaptic cleft. The neurotransmitter then binds to receptors embedded in the postsynaptic membrane, causing them to enter an activated state. Depending on the type of receptor, the resulting effect on the postsynaptic cell may be excitatory, inhibitory, or modulatory in more complex ways. For example, release of the neurotransmitter acetylcholine at a synaptic contact between a motor neuron and a muscle cell induces rapid contraction of the muscle cell. The entire synaptic transmission process takes only a fraction of a millisecond, although the effects on the postsynaptic cell may last much longer (even indefinitely, in cases where the synaptic signal leads to the formation of a memory trace). Structure of a typical chemical synapse

 

 Postsynaptic

 There are literally hundreds of different types of synapses. In fact, there are over a hundred knoweurotransmitters, and many of them have multiple types of receptors. Many synapses use more than one neurotransmitter—a common arrangement is for a synapse to use one fast-acting small-molecule neurotransmitter such as glutamate or GABA, along with one or more peptide neurotransmitters that play slower-acting modulatory roles. Molecular neuroscientists generally divide receptors into two broad groups: chemically gated ion channels and second messenger systems. When a chemically gated ion channel is activated, it forms a passage that allow specific types of ion to flow across the membrane. Depending on the type of ion, the effect on the target cell may be excitatory or inhibitory. When a second messenger system is activated, it starts a cascade of molecular interactions inside the target cell, which may ultimately produce a wide variety of complex effects, such as increasing or decreasing the sensitivity of the cell to stimuli, or even altering gene transcription.

 

According to a rule called Dale’s principle, which has only a few known exceptions, a neuron releases the same neurotransmitters at all of its synapses. This does not mean, though, that a neuron exerts the same effect on all of its targets, because the effect of a synapse depends not on the neurotransmitter, but on the receptors that it activates. Because different targets can (and frequently do) use different types of receptors, it is possible for a neuron to have excitatory effects on one set of target cells, inhibitory effects on others, and complex modulatory effects on others still. Nevertheless, it happens that the two most widely used neurotransmitters, glutamate and GABA, each have largely consistent effects. Glutamate has several widely occurring types of receptors, but all of them are excitatory or modulatory. Similarly, GABA has several widely occurring receptor types, but all of them are inhibitory. Because of this consistency, glutamatergic cells are frequently referred to as “excitatory neurons”, and GABAergic cells as “inhibitory neurons”. Strictly speaking this is an abuse of terminology—it is the receptors that are excitatory and inhibitory, not the neurons—but it is commonly seen even in scholarly publications.

 

One very important subset of synapses are capable of forming memory traces by means of long-lasting activity-dependent changes in synaptic strength. The best-known form of neural memory is a process called long-term potentiation (abbreviated LTP), which operates at synapses that use the neurotransmitter glutamate acting on a special type of receptor known as the NMDA receptor. The NMDA receptor has an “associative” property: if the two cells involved in the synapse are both activated at approximately the same time, a channel opens that permits calcium to flow into the target cell. The calcium entry initiates a second messenger cascade that ultimately leads to an increase in the number of glutamate receptors in the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks or longer. Since the discovery of LTP in 1973, many other types of synaptic memory traces have been found, involving increases or decreases in synaptic strength that are induced by varying conditions, and last for variable periods of time. Reward learning, for example, depends on a variant form of LTP that is conditioned on an extra input coming from a reward-signalling pathway that uses dopamine as neurotransmitter. All these forms of synaptic modifiability, taken collectively, give rise to neural plasticity, that is, to a capability for the nervous system to adapt itself to variations in the environment.

he autonomic nervous system (ANS or visceral nervous system or involuntary nervous system) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiratory rate, salivation, perspiration, pupillary dilation, micturition (urination), and sexual arousal. Most autonomous functions are involuntary but a number of ANS actions can work alongside some degree of conscious control. Everyday examples include breathing, swallowing, and sexual arousal, and in some cases functions such as heart rate.

 

Within the brain, the ANS is located in the medulla oblongata in the lower brainstem. The medulla’s major ANS functions include respiration (the respiratory control centre, or “rcc”), cardiac regulation (the cardiac control centre, or “ccc”), vasomotor activity (the vasomotor centre or “vmc”), and certain reflex actions (such as coughing, sneezing, vomiting and swallowing). These then subdivide into other areas and are also linked to ANS subsystems and nervous systems external to the brain. The hypothalamus, just above the brain stem, acts as an integrator for autonomic functions, receiving ANS regulatory input from the limbic system to do so.

 

The ANS is classically divided into two subsystems: the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) which operate independently in some functions and interact co-operatively in others. In many cases the two have “opposite” actions where one activates a physiological response and the other inhibits it. An older simplification of the sympathetic and parasympathetic nervous systems as “excitory” and “inhibitory” was overturned due to the many exceptions found. A more modern characterisation is that the sympathetic nervous system is a “quick response mobilising system” and the parasympathetic is a “more slowly activated dampening system”, but even this has exceptions, such as in sexual arousal and orgasm where both play a role. The enteric nervous system is also sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

 

ANS functions can generally be divided into sensory (afferent) and motor (efferent) subsystems. Within both there are inhibitory and excitatory synapses between neurons. Relatively recently, a third subsystem of neurons that have beeamed ‘non-adrenergic and non-cholinergic’ neurons (because they use nitric oxide as a neurotransmitter) have been described and found to be integral in autonomic function, particularly in the gut and the lungs.

 

Anatomy

ANS innervation is divided into sympathetic nervous system and parasympathetic nervous system divisions. The sympathetic division has thoracolumbar “outflow”, meaning that the neurons begin at the thoracic and lumbar (T1-L2) portions of the spinal cord. The parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves (CN 3, CN7, CN 9, CN10) and sacral (S2-S4) spinal cord.

 

The ANS is unique in that it requires a sequential two-neuron efferent pathway; the preganglionic neuron must first synapse onto a postganglionic neuron before innervating the target organ. The preganglionic, or first, neuron will begin at the “outflow” and will synapse at the postganglionic, or second, neuron’s cell body. The postganglionic neuron will then synapse at the target organ.

 

Sympathetic division

The sympathetic division (thoracolumbar outflow) consists of cell bodies in the lateral horn of spinal cord (intermediolateral cell columns) from T1 to L2. These cell bodies are GVE (general visceral efferent) neurons and are the preganglionic neurons. There are several locations upon which preganglionic neurons can synapse for their postganglionic neurons:

·        Paravertebral ganglia (3) of the sympathetic chain (these run on either side of the vertebral bodies)

·        Cervical Ganglia (3)

·        Thoracic Ganglia (12) and Rostral Lumbar Ganglia (2 or 3)

·        Caudal Lumbar Ganglia and Pelvic Ganglia

·        Prevertebral ganglia (celiac ganglion, aorticorenal ganglion, superior mesenteric ganglion, inferior mesenteric ganglion)

·        Chromaffin cells of [adrenal medulla] (this is the one exception to the two-neuron pathway rule: synapse is direct onto the target cell bodies)

 

These ganglia provide the postganglionic neurons from which innervation of target organs follows. Examples of splanchnic (visceral) nerves are:

·        Cervical cardiac nerves & thoracic visceral nerves which synapse in the sympathetic chain

·        Thoracic splanchnic nerves (greater, lesser, least) which synapse in the prevertebral ganglion

·        Lumbar splanchnic nerves which synapse in the prevertebral ganglion

·        Sacral splanchnic nerves which synapse in the inferior hypogastric plexus

 

These all contain afferent (sensory) nerves as well, known as GVA (general visceral afferent) neurons.

 

Parasympathetic division

The parasympathetic division (craniosacral outflow) consists of cell bodies from one of two locations: brainstem (Cranial Nerves III, VII, IX, X) or sacral spinal cord (S2, S3, S4). These are the preganglionic neurons, which synapse with postganglionic neurons in these locations:

Parasympathetic ganglia of the head (Ciliary (CN III), Submandibular (CN VII), Pterygopalatine (CN VII), Otic (CN IX))

In or near wall of organ innervated by Vagus (CN X), Sacral nerves (S2, S3, S4))

 

These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are:

The preganglionic parasympathetic splanchnic (visceral) nerves

Vagus nerve, which wanders through the thorax and abdominal regions innervating, among other organs, the heart, lungs, liver and stomach.

Functions of the brain

 

The brain is made up of several parts. Each part has a certain function:

 

Cerebral Cortex

 

Thought , voluntary movement , language, reasoning and perception are the major functions of the cerebral cortex.

 

 Cortex literally means “bark” (of a tree) in latin and is so termed because it is a sheet of tissue that makes up the outer layer of the brain.

 

 The thickness of the cerebral cortex is between 2 to 6 mm. The right and left sides of the cerebral cortex are connected by a thick band of nerve fibers called the “corpus callosum.”

 

 The cortex has numerous grooves and bumps to increase its surface area. A bump or bulge on the cortex is called a gyrus (the plural of the word gyrus is “gyri”) and a groove is called a sulcus (the plural of the word sulcus is “sulci”).

 

Cerebellum

 

The major functions of the cerebellum are maintenance of movement, balance and posture. The word “cerebellum” comes from the Latin word for “little brain.” It is divided into two parts or hemispheres and has a cortex that covers the hemispheres.

 

Hypothalamus

 

The hypothalamus regulates the body temperatures, emotions and hunger, thirst and controls the circadian rhythms.

 

 This pea sized organ is in control of body temperature. It acts like a “thermostat” by sensing changes in body temperature and sends out signals to adjust the temperature.

 

Brain stem or Medulla oblongata

 

This area is vital for life as it controls breathing, heart rate and blood pressure. The brain stem comprises of the medulla, pons, tectum, reticular formation and tegmentum.

 

Thalamus

 

Works by integrating sensory information and motor information. The thalamus receives sensory information and relays this information to the cerebral cortex.

 

 The cerebral cortex also sends information to the thalamus which then transmits this information to other areas of the brain and spinal cord.

 

Limbic System

 

This part of the brain includes amygdala, the hippocampus, mammillary bodies and cingulate gyrus. These help in controlling the emotional response. The hippocampus is also important for learning and memory.

 

Basal Ganglia

 

This part works in maintaining balance and movements. It includes structures like the globus pallidus, caudate nucleus, subthalamic nucleus, putamen and substantia nigra.

 

Midbrain

 

This part of the brain has sites controlling vision, hearing, eye movement and general body movement. The structures that are part of the midbrain are superior and inferior colliculi and red nucleus.

Functions of the Cerebrospinal nervous system

 

This system has 12 pairs of cranial nerves.  These are attached to the brain and have specific functions. Each cranial nerve leaves the skull through an opening at its base. 

 

 The nerves and their functions include:

·        Olfactory – for smell

·        Optic – Sight

·        Oculomotor – Movement of the eyeball, lens, and  pupils

·        Trochlear – Movement of the Superior oblique muscle of the eye

·        rigeminal – Innervates the eyes, cheeks and the jaw areas and controls chewing

·        Abducens – Moves the eye outward

·        Facial – Controls muscles of the face, scalp, ears; controls salivary glands; receives taste sensation from the anterior two-thirds of the tongue

·        Acoustic – Hearing and maintenance of balance

·        Glossopharyngeal – Taste sensation from the back of the tongue and throat

·        Vagus – Innervates the chest and abdominal organs

·        Spinal Accessory – movement of head and shoulders

·        Hypoglossal – Controls muscles of tongue

 

Functions of the Autonomic nervous system

The autonomic nervous system is divided into sympathetic and parasympathetic nervous systems. These two systems have opposite effects on the same set of organs.

 

 The sympathetic nervous system is important during an emergency and is associated with “fight or flight reaction”. The energy is directed away from digestion, there is dilation of pupils, increased heart rate, increased perspiration and salivation, increased breathing etc.

 

 The parasympathetic nervous system is associated with a relaxed state. The pupils contract, energy is diverted for digestion of food, heart rate slows etc.

Nervous System Disorders Glossary

 

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