The nervous system can be characterized according to the functional and anatomical principles.
According to the functional principle the nervous system (NS) consists of:
1. the somatic nervous system which is responsible for coordinating voluntary body movements (i.e. activities that are under conscious control).
2. the autonomic (visceral) nervous system, which is responsible for coordinating involuntary functions, such as breathing and digestion.
The autonomic nervous system is subdivided into parasympathetic and sympathetic parts. In both parts there are afferent and efferent nerve fibers. The activities of the sympathetic part of the autonomic system prepare the body for an emergency. It accelerates the heart rate, causes constriction of the peripheral blood vessels, and raises the blood pressure. It brings about a redistribution of the blood, so that blood leaves the areas of the skin and intestine and becomes available to the brain, heart, and skeletal muscles. At the same time it inhibits peristalisis of the intestinal tract and closes the sphincters. The activities of the parasympathetic part of the autonomic system are aimed at conserving and restoring energy. It slows the heart rate, increases peristalisis of the intestine, increases glandular activity, and opens the sphincters. In turn, these divisions of the nervous system can be further divided according to the direction in which they conduct nerve impulses: (1) Afferent system by sensory neurons, which carries impulses from a somatic receptor to the central nervous system (CNS ); (2) Efferent system by motor neurons, which carries impulses from the CNS to an effector; (3) Relay system by interneurons (also called ‘relay neurons’), which transmit impulses between the sensory and motor neurons both in the central nervous system (CNS) and the periphery nervous system (PNS).
According to the anatomical principle the nervous system (NS) consists of:
1. the central nervous system (CNS) (which consists of the brain and spinal cord);
2. the peripheral nervous system (PNS) (which consists of the cranial and spinal nerves and their associated ganglia.
Neurons (specialized cells) generate and conduct impulses between and within the two systems. The peripheral nervous system is composed of sensory neurons and the neurons that connect them to the spinal cord and brain, which make up the central nervous system. In response to stimuli, sensory neurons generate and propagate signals to the central nervous system which then processes and conducts signals back to the muscles and glands. The neurons of the nervous systems are interconnected in complex arrangements and use electrochemical signals and neurotransmitters to transmit impulses from one neuron to the next.
The central nervous system is the largest part of the nervous system, and includes the brain and spinal cord. The PNS is a regional term for the collective nervous structures that do not lie in the CNS. The bodies of the nerve cells lie in the CNS, either in the brain or the spinal cord, and their axons (parts of neurons) extend through the limbs and the flesh of the torso.
(Fig.1. Central Nervous System:1. brain, 2. CNS (brain and spinal cord), 3. spinal cord.)
(Fig.2. The autonomic nervous system:
blue = parasympathetic,
red = sympathetic)
(click the picture to enlarge)
(Fig. 3. Nervous System)
(click the picture to enlarge)
(Fig.4. The diagram of the nervous system)
(click the picture to enlarge)
The human brain is the center of the human nervous system and is a highly complex organ. The human brain contains roughly 100 billion neurons, linked with up to 10,000 synaptic connections each. Each cubic millimeter of cerebral cortex contains roughly one billion synapses. These neurons communicate with one another by means of long protoplasmic fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body and target them to specific recipient cells.
Cerebral Cortex - is a structure within the brain that plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It constitutes the outermost layer of the cerebrum. It has a grey color. Grey matter is formed by neurons and their unmyelinated fibers, whereas the white matter below the grey matter of the cortex is formed predominantly by myelinated axons interconnecting different regions of the central nervous system. The human cerebral cortex is about 1-5 mm thick. The surface of the cerebral cortex is folded in large mammals, such that more than two-thirds of the cortical surface is buried in the grooves, called "sulci."
Corpus Callosum - is a structure of the brain that connects the left and right cerebral hemispheres facilitating communication between the two hemispheres. It is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is a wide, flat bundle of axons beneath the cortex. Much of the inter-hemispheric communication in the brain is conducted across the corpus callosum.
Thalamus - is a paired and symmetrical part of the brain. It constitutes the main part of the diencephalon. In normal humans, the two thalami are prominent bulb-shaped masses, about 5.7 cm in length, located obliquely (about 30°) and symmetrically on each side of the third ventricle. The thalamus is known to have multiple functions: process and relay sensory information selectively to various parts of the cerebral cortex, regulating states of sleep and wakefulness, regulating arousal, the level of awareness, and activity. Damage to the thalamus can lead to permanent coma.
(Fig. 6. Thalamus)(click the picture to enlarge)
Cerebellum - (Latin for little brain) is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control.
(Fig. 7. Cerebellum and surrounding regions; sagittal view of one hemisphere.
A: Midbrain. B: Pons. C: Medulla. D: Spinal cord. E: Fourth ventricle. F: Arbor vitae. G: Amigdala. H: Anterior lobe. I: Posterior lobe.)(click the picture to enlarge)
Hypothalamus – is a part of diecephalon. It is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland (hypophysis). The hypothalamus (the Greek for ‘under the thalamus’) is located below the thalamus, just above the brain stem. In humans, it is roughly the size of an almond. The hypothalamus is responsible for certain metabolic processes and other activities of the Autonomic Nervous System. It synthesizes and secretes neurohormones, oftencalled hypothalamic-releasinghormones, and these in turn stimulate or inhibit the secretion of pituitary hormones. The hypothalamus controls body temperature, hunger, thirst, fatigue, and circadian cycles (a circadian rhythm is a roughly-24-hour cycle in the biochemical, physiological or behavioral processes of living entities).
(Fig.8. Diecephalon)(click the picture to enlarge)
Hippocampus - belongs to the limbic system and plays important roles in long term memory and spatial navigation. Like the cerebral cortex, with which it is closely associated, it is a paired structure, with mirror-image halves in the left and right sides of the brain. The hippocampus is located inside the medial temporal lobe, beneath the cortical surface. It has a curved shape.
(Fig. 9. Hippocampus)(click the picture to enlarge)
The brainstem (brain stem) is the lower part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves. Though small, this is an extremely important part of the brain as the nerve connections of the motor and sensory systems from the main part of the brain to the rest of the body pass through the brain stem. This includes the corticospinal tract (motor), the posterior column-medial lemniscus pathway (fine touch, vibration sensation and proprioception; aproprioception is the reception of stimuli produced within the organism) and the spinothalamic tract (pain, temperature, itch and crude touch). The brain stem also plays an important role in the regulation of cardiac and respiratory function. It also regulates the central nervous system, and is pivotal in maintaining consciousness and regulating the sleep cycle. The brain stem is described as the medulla oblongata (myelencephalon) and pons (part of metencephalon), however sometimes midbrain (mesencephalon) is included.
(Fig.10. Brain Stem)(click the picture to enlarge)
The cerebral cortex is nearly symmetric, with left and right hemispheres and each hemisphere is conventionally divided into four ‘lobes’: the frontal lobe, parietal lobe, temporal lobe, and occipital lobe.
(Fig.11. The four lobes of the cerebral cortex)(click the picture to enlarge)
1. Frontal lobe - conscious thought; damage can result in mood changes;
2. Parietal lobe - plays important roles in integrating sensory information from various senses, and in the manipulation of objects; portions of the parietal lobe are involved in visuospatial processing.
3. Occipital lobe - sense of sight; lesions can produce hallucinations.
4. Temporal lobe - senses of smell and sound, as well as processing of complex stimuli like faces and scenes.
The insula is a portion of cortex in between and covered by the temporal and parietal lobes. Some consider it as a separate lobe, but others as a part of the limbic structure deep in the brain.
(Fig. 12. Insula (on the right of the image and in the middle))(click the picture to enlarge)
Cerebellum links sensory input with motion; this is especially involved in maintaining balance.
Each of the lobes of the telencephalon is divided in half making the left and right cerebral hemispheres. The two hemispheres are connected with matter called the corpus callosum which allows the two lobes to communicate information to each other. It is the left hemisphere which receives and sends information to the right side of the body, and the right hemisphere which deals with the left side of the body.
The limbic system includes many structures of the brain.
The following structures are, or have been considered to be, part of the limbic system:
-Amygdala: Involved in signaling the cortex of motivationally significant stimuli such as those related to reward and fear in addition to social functions such as mating.
-Hippocampus: Required for the formation of long-term memories and implicated in maintenance of cognitive maps for navigation.
-Parahippocampal gyrus: Plays a role in the formation of spatial memory.
-Cingulate gyrus: Autonomic functions regulating heart rate, blood pressure and cognitive and attentional processing.
-Fornix: carries signals from the hippocampus to the mammillary bodies and septal nuclei.
-Hypothalamus: Regulates the autonomic nervous system via hormone production and release. Affects and regulates blood pressure, heart rate, hunger, thirst, sexual arousal, and the sleep/wake cycle.
-Thalamus: The ‘relay station’ to the cerebral cortex .
(Fig. 14. The view of the brain from the underside: amygdale, putamen, thalamus)(click the picture to enlarge)
In addition, these structures are sometimes also considered to be part of the limbic system:
-Mammillary body: important for the formation of memory.
-Pituitary gland: secretes hormones regulating homeostasis.
-Dentate gyrus: thought to contribute to new memories and to regulate happiness.
-Entorhinal cortex: is an important memory center in the brain.
-Piriform cortex: receives smell input in the olfactory system.
-Fornicate gyrus: region encompassing the cingulate, hippocampus, and parahippocampal gyrus.
-Olfactory bulb: olfactory sensory input.
-Nucleus accumbens: involved in reward, pleasure, and addiction.
-Orbitofrontal cortex: required for decision making.
The cerebral cortex is essentially a sheet of neural tissue, folded in a way that allows a large surface area to fit within the confines of the skull. Each cerebral hemisphere, in fact, has a total surface area of about 1.3 square feet. Anatomists call each cortical fold a sulcus, and the smooth area between folds a gyrus. Most human brains show a similar pattern of folding, but there are enough variations in the shape and placement of folds to make every brain unique. Each sulcus (pl. sulci ), or gyrus (pl. gyri), has a name.
(Fig. 16. The names of gyri of the cerebral cortex)(click the picture to enlarge)
A gyrus (pl. gyri) is a ridge on the cerebral cortex. It is generally surrounded by one or more sulci.
A sulcus (Latin: furrow, pl. sulci) is a depression or fissure in the surface of the brain. It surrounds the gyri. Large furrows (sulci) that divide the brain into lobes are often called fissures. The large furrow that divides the two hemispheres – the interhemispheric fissure.
(Fig.17. Gyri and sulci)(click the picture to enlarge)
“The gray matter corresponds largely to the collection of nerve cell bodies, while the white matter corresponds to axons, or nerve fibers, emanating from call bodies in the gray matter.
The gray matter comes in two varieties. In the first variety the neurons are layered as in a cake and form a cortex. Examples are the cerebral cortex which covers the cerebral hemispheres, and the cerebellar cortex which envelops the cerebellum. In the second variety of gray matter the neurons are not layered and are organized instead like a cashew nuts inside a bowl. They form a nucleus. There are large nuclei, such as the caudate, putamen, and pallidum, quietly hidden in the depth of each hemisphere; or the amygdale, hidden inside each temporal lobe; there are large collections of smaller nuclei, such as those that form the thalamus; and small individual nuclei, such as the substantia nigra or the nucleus ceruleus, located in the brain stem (…).
The thickness of this multilayer blanket is about 3 millimeters, and the layers are parallel to one another and to the brain’s surface. All gray matter below the cortex (nuclei, large and small, and the cerebellar cortex) is known as subcortical. The evolutionarily modern part of cerebral cortex is called the neocortex. Most of the evolutionary older cortex is known as limbic cortex.” (Antonio Damasio, Descartes’ Error, pp.26-27).
(Fig. 18. The organization of the gray matter.
A – the neurons are layered as in a cake and form a cortex;
B – the neurons are not layered but they are organized instead like a ‘cashew nuts inside a bowl’ and form a nucleus.)(click the picture to enlarge)
Different parts of the cerebral cortex are involved in different cognitive and behavioral functions.
One of the most widely used schemes came from Brodmann, who assigned numbers from 1 to 52 to brain areas (later anatomists have subdivided many of them).
(Fig.19. Lateral surface of the brain with Brodmann's areas numbered)(click the picture to enlarge)
(Fig.20. Medial surface of the brain with Brodmann's areas numbered)(click the picture to enlarge)
Brodmann areas for human and non-human primates http://en.wikipedia.org/wiki/Brodmann_area
- Areas 3, 1 & 2 - Primary Somatosensory Cortex (frequently referred to as Areas 3, 1, 2 by convention)
- Area 4 - Primary Motor Cortex
- Area 5 - Somatosensory Association Cortex
- Area 6 - Premotor cortex and Supplementary Motor Cortex (Secondary Motor Cortex)(Supplementary motor area)
- Area 7 - Somatosensory Association Cortex
- Area 8 - Includes Frontal eye fields
- Area 9 - Dorsolateral prefrontal cortex
- Area 10 - Anterior prefrontal cortex (most rostral part of superior and middle frontal gyri)
- Area 11 - Orbitofrontal area (orbital and rectus gyri, plus part of the rostral part of the superior frontal gyrus)
- Area 12 - Orbitofrontal area (used to be part of BA11, refers to the area between the superior frontal gyrus and the inferior rostral sulcus)
- Area 13 and Area 14* - Insular cortex
- Area 15* - Anterior Temporal Lobe
- Area 17 - Primary visual cortex (V1)
- Area 18 - Secondary visual cortex (V2)
- Area 19 - Associative visual cortex (V3)
- Area 20 - Inferior temporal gyrus
- Area 21 - Middle temporal gyrus
- Area 22 - Superior temporal gyrus, of which the caudal part is usually considered to contain the Wernicke's area
- Area 23 - Ventral Posterior cingulate cortex
- Area 24 - Ventral Anterior cingulate cortex
- Area 25 - Subgenual cortex
- Area 26 - Ectosplenial area
- Area 27 - Piriform cortex
- Area 28 - Posterior Entorhinal Cortex
- Area 29 - Retrosplenial cingulate cortex
- Area 30 - Part of cingulate cortex
- Area 31 - Dorsal Posterior cingulate cortex
- Area 32 - Dorsal anterior cingulate cortex
- Area 33 - Part of anterior cingulate cortex
- Area 34 - Anterior Entorhinal Cortex (on the Parahippocampal gyrus)
- Area 35 - Perirhinal cortex (on the Parahippocampal gyrus)
- Area 36 - Parahippocampal cortex (on the Parahippocampal gyrus)
- Area 37 - Fusiform gyrus
- Area 38 - Temporopolar area (most rostral part of the superior and middle temporal gyri)
- Area 39 - Angular gyrus, considered by some to be part of Wernicke's area
- Area 40 - Supramarginal gyrus considered by some to be part of Wernicke's area
- Areas 41 & 42 - Primary and Auditory Association Cortex
- Area 43 - Subcentral area (between insula and post/precentral gyrus)
- Area 44 - pars opercularis, part of Broca's area
- Area 45 - pars triangularis Broca's area
- Area 46 - Dorsolateral prefrontal cortex
- Area 47 - Inferior prefrontal gyrus
- Area 48 - Retrosubicular area (a small part of the medial surface of the temporal lobe)
- Area 52 - Parainsular area (at the junction of the temporal lobe and the insula)
(*) Area only found in non-human primates.
(Fig. 21. Areas and functional attribution)(click the picture to enlarge)
Each hemisphere of the brain interacts mainly with one half of the body, but for reasons that are unclear, the connections are crossed: the left side of the brain interacts with the right side of the body, and vice versa. Motor connections from the brain to the spinal cord, and sensory connections from the spinal cord to the brain, both cross the midline at brainstem levels. Visual input follows a more complex rule: the optic nerves from the two eyes come together at a point called the optic chiasm, and half of the fibers from each nerve split off to join the other. The result is that connections from the left half of the retina, in both eyes, go to the left side of the brain, whereas connections from the right half of the retina go to the right side of the brain. Because each half of the retina receives light coming from the opposite half of the visual field, the functional consequence is that visual input from the left side of the world goes to the right side of the brain, and vice versa. Thus, the right side of the brain receives somatosensory input from the left side of the body, and visual input from the left side of the visual field - an arrangement that presumably is helpful for visuomotor coordination.
(Fig. 22. The corpus callosum, a nerve bundle connecting the two cerebral hemispheres)
The two cerebral hemispheres are connected by a very large nerve bundle called the corpus callosum, which crosses the midline above the level of the thalamus. There are also two much smaller connections, the anterior commisure and hippocampal commisure, as well as many subcortical connections that cross the midline. But the corpus callosum is the main avenue of communication between the two hemispheres. It connects each point on the cortex to the mirror-image point in the opposite hemisphere, and also connects to functionally related points in different cortical areas.
In most respects, the left and right sides of the brain are symmetrical in terms of function. For example, the counterpart of the left-hemisphere motor area controlling the right hand is the right-hemisphere area controlling the left hand. There are, however, several very important exceptions, involving language and spatial cognition. In most people, the left hemisphere is ‘dominant’ for language: a stroke that damages a key language area in the left hemisphere can leave the victim unable to speak or understand, whereas equivalent damage to the right hemisphere would cause only minor impairment to language skills.
The cell is the structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. Each cell is at least somewhat self-contained and self-maintaining: it can take in nutrients, convert these nutrients into energy, carry out specialized functions, and reproduce as necessary. Each cell stores its own set of instructions for carrying out each of these activities. Eukaryotic cells (eukaryote means having a nucleus) contain membrane-bound compartments in which specific metabolic activities take place. Most important among these is the presence of a cell nucleus, a membrane-delineated compartment that houses the eukaryotic cell’s DNA.
A neuron (nerve cell) is an excitable cell in the nervous system that processes and transmits information by electrochemical signalling.
A number of specialized types of neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the sensory organs that then send signals to the spinal cord and brain. Motor neurons receive signals from the brain and spinal cord and cause muscle contractions and affect glands. The complexity and diversity in nervous systems is dependent on the interconnections between neurons, which rely on a limited number of different signals transmitted within the neurons to other neurons or to muscles and glands. The signals are produced and propagated by chemical ions that produce an electrical charge that moves along the neuron. Neurons exist in a number of different shapes and sizes and can be classified by their morphology and function.
(Fig. 23. Neuron)(click the picture to enlarge)
A typical neuron consists of a cell body called the soma and a long thin axon which is covered by the myelin sheath. Around the cell body is a branching dendritic tree that receives signals from other neurons. The end of the axon (axon terminal) releases neurotransmitters into a gap called the synaptic cleft between the terminals and the dendrites of the next neuron. The anatomy and the properties of the surface membrane determine the behavior of a neuron. The surface membrane is not uniform over the entire length of a neuron, but is modified in specific areas: some regions secrete transmitter substances while other areas respond to the transmitter. Other areas of the neuron membrane have passive electrical properties that affect capacitance and resistance. Within the neuron membrane there are gated ion channels that vary in type, including fast response sodium channels that are voltage-gated and are used to send rapid signals.
Neurons communicate by chemical and electrical synapses in a process known as synaptic transmission. The fundamental process that triggers synaptic transmission is the action potential, a propagating electrical signal that is generated by exploiting the electrically excitable membrane of the neuron. This is also known as a wave of depolarization.
Named after the German physiologist Theodor Schwann, Schwann cells are a variety of glial cell that keep peripheral nerve fibres (both myelinated and unmyelinated) alive. There is a string of Schwann cells along the length of the axon, much like a string of sausages. In myelinated axons, Schwann cells form the myelin sheath. The sheath is not continuous. The gaps between adjacent Schwann cells are called the nodes of Ranvier.
Nodes of Ranvier are the gaps (approximately 1 micrometer in length) between the myelin sheaths. A myelin sheath is a many-layered coating, largely composed of a fatty substance called myelin, that wraps around the axon of a neuron and very efficiently insulates it. At nodes of Ranvier, the axonal membrane is uninsulated and therefore capable of generating electrical activity.
Glial cells (neuroglia or glia, 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, there is roughly one glia for every neuron with a ratio of about two neurons for every three glia in the cerebral gray matter. Glial cells provide support and protection for neurons. The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons. They also modulate neurotransmission.
Some glia function primarily as the physical support for neurons. Others regulate the internal environment of the brain, especially the fluid surrounding neurons and their synapses, and provide nutrition to nerve cells. Glia have important developmental roles, guiding migration of neurons in early development, and producing molecules that modify the growth of axons and dendrites. Recent findings in the hippocampus and cerebellum have indicated that glia are also active participants in synaptic transmission, regulating clearance of neurotransmitter from the synaptic cleft, releasing factors such as ATP (ATP is a multifunctional nucleotide, and plays an important role in cell biology) which modulate presynaptic function, and even releasing neurotransmitters themselves.
Fully differentiated neurons are permanently amitotic (i.e. a cell does not split forming new sets of neurons) unlike glia; however, recent research shows that additional neurons throughout the brain can originate from neural stem cells found throughout the brain but in particularly high concentrations in the subventricular zone and subgranular zone through the process of neurogenesis (subventricular zone is a paired brain structure situated throughout the lateral walls of the lateral ventricles; subgranular zone is a brain region in the dentate gyrus, deep within the hippocampal parenchyma).
Neurons are highly specialized for the processing and transmission of cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there is, as expected, a wide variety in the shape, size, and electrochemical properties of neurons. For instance, the soma of a neuron can vary from 4 to 100 micrometers in diameter.
- The soma is the central part of the neuron. It contains the nucleus of the cell, and most protein synthesis occurs there. The nucleus ranges from 3 to 18 micrometers in diameter.
- The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and structure is referred to as a dendritic tree. This is where the majority of input to the neuron occurs. Information outflow (i.e. from dendrites to other neurons) can also occur, but not across chemical synapses; there, the back flow of a nerve impulse is inhibited by the fact that an axon does not possess chemoreceptors and dendrites cannot secrete neurotransmitter chemicals. This unidirectionality of a chemical synapse explains why nerve impulses are conducted only in one direction.
- The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away from the soma (and also carries some types of information back to it). Many neurons have only one axon, but this axon may - and usually will - undergo extensive branching, enabling communication with many target cells. The part of the axon where it emerges from the soma is called the axon hillock. Besides being an anatomical structure, the axon hillock is also the part of the neuron that has the greatest density of voltage-dependent sodium channels. This makes it the most easily-excited part of the neuron and the spike initiation zone for the axon. While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons.
- The axon terminal contains synapses, specialized structures where neurotransmitter chemicals are released in order to communicate with target neurons.
(Fig. 25. The axon, the process of growth)
Axons and dendrites in the central nervous system are typically only about one micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motoneuron can be over a meter long, reaching from the base of the spine to the toes. There can be three main types of neurons according to their direction:
A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the target neuron is determined not by the source neuron or by the neurotransmitter, but by the type of receptor that is activated. A neurotransmitter can be thought of as a key, and a receptor as a lock. Receptors can be classified broadly as excitatory (causing an increase in firing rate), inhibitory (causing a decrease in firing rate), or modulatory (causing long-lasting effects not directly related to firing rate).
In fact, however, the two most common neurotransmitters in the brain, glutamate and GABA (gamma-aminobutyric acid) have actions that are largely consistent. Glutamate acts on several different types of receptors, but most of them have effects that are excitatory. Similarly GABA acts on several different types of receptors, but all of them have effects (in adult animals, at least) that are inhbitory. Because of this consistency, it is common for neuroscientists to simplify the terminology by referring to cells that release glutamate as ‘excitatory neurons’, and cells that release GABA as ‘inhibitory neurons’. Since well over 90% of the neurons in the brain release either glutamate or GABA, these labels encompass the great majority of neurons. There are also other types of neurons that have consistent effects on their targets, for example ‘excitatory’ motor neurons in the spinal cord that release acetylcholine, and ‘inhibitory’ spinal neurons that release glycine.
The distinction between excitatory and inhibitory neurotransmitters is not absolute, however. Rather, it depends on the class of chemical receptors present on the target neuron. In principle, a single neuron, releasing a single neurotransmitter, can have excitatory effects on some targets, inhibitory effects on others, and modulatory effects on other ones. For example, photoreceptors in the retina constantly release the neurotransmitter glutamate in the absence of light. So-called OFF bipolar cells are, like most neurons, excited by the released glutamate. However, neighboring target neurons called ON bipolar cells are instead inhibited by glutamate, because they lack the typical ionotropic glutamate receptors and instead express a class of inhibitory metabotropic glutamate receptors. When light is present, the photoreceptors cease releasing glutamate, which relieves the ON bipolar cells from inhibition, activating them; this simultaneously removes the excitation from the OFF bipolar cells, silencing them.
Classification by neurotransmitter production
Neurons differ in the type of neurotransmitter they manufacture. Some examples are:
cholinergic neurons - acetylcholine
GABAergic neurons – gamma aminobutyric acid
glutamatergic neurons - glutamate
dopaminergic neurons - dopamine
serotonergic neurons - serotonin
Neurons communicate with one another via synapses, where the axon terminal looking like a bouton (terminals located along the length of the axon) of one cell impinges upon another neuron's dendrite, soma or, less commonly, axon (axodentric, axosomatic and axoaxonic synapses). Neurons such as Purkinje cells in the cerebellum can have over 1000 dendritic branches, making connections with tens of thousands of other cells; other neurons have only one or two dendrites, each of which receives thousands of synapses. Synapses can be excitatory or inhibitory and will either increase or decrease activity in the target neuron. Some neurons also communicate via electrical synapses, which are direct, electrically-conductive junctions between cells.
In a chemical synapse, the process of synaptic transmission is as follows: when an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron.
An electrical synapse is a mechanical and electrically conductive link between two neuron cells that is formed at a narrow gap between the pre- and postsynaptic cells known as a gap junction. At gap junctions, such cells approach within about 3.5 nm of each other, a much shorter distance than the 20 to 40 nm distance that separates cells at chemical synapses (nm - nanometer, equal to a thousand-millionth of a meter). In organisms, electrical synapse-based systems co-exist with chemical synapses.
Compared to chemical synapses, electrical synapses conduct nerve impulses faster, but unlike chemical synapses they do not have gain (the signal in the post synaptic neuron is always smaller than that of the originating neuron). Electrical synapses are often found in neural systems that require the fastest possible response, such as defensive reflexes. An important characteristic of electrical synapses is that most of the time, they are bidirectional, i.e. they allow impulse transmission in either direction. However, some gap junctions do allow for communication in only one direction. The synaptic delay for a chemical synapse is typically about 2 ms, while the synaptic delay for an electrical synapse may be about 0.2 ms (‘ms’ - millisecond, a unit of time equal to one thousandth of a second).
(Fig. 27. Electrical synapse)(click the picture to enlarge)
The human brain has a huge number of synapses. Each of the 1011 (one hundred billion) neurons has on average 7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about 1015 synapses (1 quadrillion). This number declines with age, stabilized by adulthood. Estimates vary for an adult, ranging from 1014 to 5 x 1014 synapses (100 to 500 trillion).
Mechanism for propagating action potentials
The cell membrane of the axon and soma contain voltage-gated ion channels which allow the neuron to generate and propagate an electrical signal (an action potential). These signals are generated and propagated by charge-carrying ions including sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+).
There are several stimuli that can activate a neuron leading to electrical activity, including pressure, stretch, chemical transmitters, and changes of the electric potential across the cell membrane. Stimuli cause specific ion-channels within the cell membrane to open, leading to a flow of ions through the cell membrane, changing the membrane potential.
To minimize metabolic expense while maintaining rapid conduction, many neurons have insulating sheaths of myelin around their axons.
The sheaths are formed by glial cells: oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to travel faster than in unmyelinated axons of the same diameter, whilst using less energy. The myelin sheath in peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of Ranvier which contain a high density of voltage-gated ion channels.
Multiple sclerosis is a neurological disorder that results from demyelination of axons in the central nervous system.
Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes graded neurotransmitter release. Such nonspiking neurons tend to be sensory neurons or interneurons, because they cannot carry signals long distances.
The conduction of nerve impulses is an example of an all-or-none response. In other words, if a neuron responds at all, then it must respond completely. The greater the intensity of stimulation does not produce a stronger signal but can produce more impulses per second. There are different types of receptor response to stimulus, slowly adapting or tonic receptors respond to steady stimulus and produce a steady rate of firing. These tonic receptors most often respond to increased intensity of stimulus by increasing their firing frequency. There are a number of other receptor types that are called quickly adapting or phasic receptors, where firing decreases or stops with steady stimulus. For example, skin when touched by an object causes the neurons to fire, but if the object maintains even pressure against the skin the neurons stop firing.
Neuroplasticity (also referred to as brain plasticity, cortical plasticity or cortical re-mapping) is the changing of neurons and the organization of their networks and so their function by experience. The brain consists of nerve cells or neurons (and glia cells) which are interconnected, and learning may happen through changing of the strength of the connections between neurons, by adding or removing connections, or by adding new cells. New findings suggest that all areas of the brain are plastic even after childhood. Environmental changes can alter behavior and cognition by modifying connections between existing neurons and via neurogenesis in the hippocampus and other parts of the brain, including the cerebellum. Decades of research have now shown that substantial changes occur in the lowest neocortical processing areas, and that these changes can profoundly alter the pattern of neuronal activation in response to experience. According to the theory of neuroplasticity, thinking, learning, and acting actually change both the brain's physical structure (anatomy) and functional organization (physiology) from top to bottom. A substantial paradigm shift is now under way.
Alzgeimer’s disease is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is the loss of short-term memory (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), skilled movements (apraxia), recognition (agnosia), and functions such as decision making and planning get impaired.
(Fig. 28. The view of a normal brain on the left and the brain with Alzgeimer’s disease on the right)(click the picture to enlarge)
Parkinson’s disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech. Parkinson's disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement, and in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. Parkinson’s disease is both chronic and progressive.
Myasthenia Gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatigability. Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine.
Demyelination is the act of demyelinating, or the loss of the myelin sheath insulating the nerves. When myelin degrades, conduction of signals along the nerve can be impaired or lost, and the nerve eventually withers. This leads to certain neurodegenerative disorders like multiple sclerosis, chronic inflammatory demyelinating polyneuropathy.
(Fig. 29. The Effect of cocain in the brain)(click the picture to enlarge)
In neuroscience, neuromodulation is the process in which several classes of neurotransmitters in the nervous system regulate diverse populations of neurons (one neuron uses different neurotransmitters to connect to several neurons). As opposed to direct synaptic transmission, in which one presynaptic neuron directly influences a postsynaptic partner (one neuron reaching one other neuron), neuromodulatory transmitters secreted by a small group of neurons diffuse through large areas of the nervous system, having an effect on multiple neurons. Examples of neuromodulators include dopamine, serotonin, acetylcholine, histamine and others.
A neuromodulator is a relatively new concept in the field, and it can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the CSF (cerebrospinal fluid), influencing (or modulating) the overall activity level of the brain. For this reason, some neurotransmitters are also considered as neuromodulators. Examples of neuromodulators in this category are serotonin and acetylcholine. Neuromodulators may alter the output of a physiological system by acting on the associated inputs.
(Fig. 27. Neuron and electrical impulses)(click the picture to enlarge)
Neurotransmitter systems are systems of neurons in the brain expressing certain types of neurotransmitters, and thus form distinct systems. Activation of the system causes effects in large volumes of the brain. The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system. Drugs targeting the neurotransmitter of such systems affects the whole system, and explains the mode of action of many drugs. Most other neurotransmitters, on the other hand, e.g. glutamate, GABA and glycine, are used very generally throughout the central nervous system.
The noradrenaline system consists of just 1500 neurons on each side of the brain, which is diminutive compared to the total amount of more than 100 billion neurons in the brain. Nevertheless, when activated, the system plays major roles in the brain, as seen in table above. Noradrenaline is released from the neurons, and acts on adrenergic receptors.
The dopamine system consists of several pathways, originating from the ventral tegmentum or substantia nigra as examples. It acts on dopamine receptors.
Parkinson’s disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, namely the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success. Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer. AMPT (alpha-methyl-p-tyrosine) prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.
The serotonin system in the CNS contains only 1% of total body serotonin, the rest being found as transmitters in the peripheral nervous system. It travels around the brain and acts on serotonin receptors. In the peripheral nervous system (such as in the gut wall) serotonin regulates vascular tone. In pharmacology Prozac is a selective serotonin reuptake inhibitor, hence potentiating the effect of naturally released serotonin.
The cholinergic system works primary by M1 receptors, but M2-, M3-, M4-, and M4- receptors are also found in the CNS.
The gamma-aminobutyric acid (GABA) system is more generally distributed throughout the brain. Nevertheless, it has an overall inhibitory effect.