Functional Morphology of Nerve Tissue

Animals respond with their internal and external environment by two types of communication systems, the chemical com­munication and neural communication. The nervous system can recognize the environmental changes, which can influ­ence the body and work in tandem with the endocrine system to respond to the events.

The nervous system is the highly complex and specialized part of the body, which harmonizes the animal’s behavior. The system is involved in thinking, making decision, crea­tion, and invention. The input system is fast and can selec­tively receive information from the body as well as from the external environment through different receptors and afferent paths. The information then reaches the brain and is stored in the memory according to the body’s need. The nervous system is morphologically and functionally divided into two components, central nervous system (CNS) and periph­eral nervous system (PNS). The central nervous system consists of the brain and spinal cord.

11.1.1 NerveTissue

The nervous system is made up of a large number of cells (over 100 billion). The cells are mainly of two types, the neurons and neuroglia or glial cells. Neurons (Greek neuron, nerve) are specialized types of excitable cells and carry electrical impulses. Thus, they are also called conducting cells. Neuroglia (Greek glia, glue) or glial cells are noncon- ductive and supporting cells of nervous system. Neurons are also called structural and functional units of the nervous system. These neurons are composed of simple elements but are interconnected in a complex way. There are numerous specialized contact areas known as synapses, which mediate signals from one neuron to others. Synapses play a vital role in the formation of complex neuronal networks designed for information processing. Neuron transmits information between cells. Neurons with a particular function are found in a particular location in the nervous system. The cell divi­sion of neurons generally stops within a few months after birth. So, nerve damage involves cell bodies, resulting in neuronal death. It causes permanent change in the structure and functions of the affected areas. But, unlike neurons, glial cells can continue to divide. This property of glial cells is crucial for their structural and functional support of neurons. Neurons as well as glial cells need a chemically stable envi­ronment. The endothelial cells of the CNS and the choroid plexus of brain help to maintain such an environment by regulating molecules secreted into the interstitial fluid and cerebrospinal fluid (CSF). The neurons have a variable number of cytoplasmic processes attached to them. These processes are of two types, axons and dendrites.

11.1.1.1 StructureofNeuron

A nerve cell with all its processes is called a neuron.

A neuron has similar functional characteristics like other cells of the body along with some specialty. It is enclosed by unit membrane, which also encloses the dendrites and the axon processes. The membrane contains receptors, ion channels, and pumps necessary for the activities of the neurons.

CellBody The part of a neuron which surrounds the nucleus is known as cell body or soma. Cell body has the major role in protein synthesis. Cell body contains the cellular components and cell organelles like other cells of the body. The nucleus is large with prominent nucleoli and has Barr bodies. The nucleus is present at the center of the cell body. The chromatin material is comparatively more active, and there is continuous transcription. The cell body contains several cytoplasmic organelles such as the mitochondria, Golgi apparatus, endoplasmic reticulum, secretory granules, ribosomes, and polysomes.

Nerve Processes Nerve processes are “fingerlike” cytoplas­mic extensions from the cell body. They are also known as nerve fibers. They are able to conduct and transmit signals.

Fig. 11.1 Structure of a typical neuron

There are two types of nerve processes, the dendrites and axon.

Dendrites: Dendrites are short, branched processes, which extend from the cell body and normally carry nerve impulses toward the cell body. Hence, they are also referred to as afferent processes. These processes are usually many in number in a single neuron, but may be single or absent altogether. Dendrites are generally shorter than the axon and more branched. They form many synapses with nearby neurons for receiving nerve signal. The branching facilitates to increase the surface area of the cell for attachment with a large number of other neurons. They receive information through many receptors present in their membranes, which bind to chemicals, known as neurotransmitters. The number of dendrites on a neuron varies. The dendrites form contacts with other neurons. There are plenty of small projections; the dendritic spines are present on their surface. It makes a complex dendritic connection, which is important for integrative functions of CNS. One neuron can attach with more than 1000 neurons through synapse. Dendrites provide input to neuron not in the form of action potential, but as local electronic potentials.

Axon: A neuron has a single axon which extends from the cell body.

11.1.1.2 Classification of Neurons

Neurons are classified into three types on the basis of their structure as well as on the basis of the functions.

11.1.1.2.1 Structural Classification

In structural classification, the neurons are classified on the basis of the number of processes of a neuron. Structurally, neurons are of three types—unipolar, bipolar, and multipolar neurons.

Unipolar neurons: Unipolar neurons have one process, which arise from the cell body and then branch into two parts, which extend in opposite directions. One part of the process extends peripherally and is associated with sen­sory reception, which is known as the peripheral process. Another part of the process extends toward the CNS, which is known as the central process. This type of neurons is mainly found in the afferent division of the PNS.

Bipolar neurons: Bipolar neurons have two processes, one axon and other being dendrites. The processes extend in opposite directions from the cell body. These types of neurons are found in the retina of the eye and the olfactory system.

Multipolar neurons: Multipolar neurons have multiple pro­cesses, one of which is axon and the rest are dendrites. Multipolar neurons are the major neuron type found in the CNS as well as the efferent division of the PNS. In humans, more than 99% of the neurons are multipolar.

11.1.1.2.2 Functional Classification

Neurons are also classified on the functional basis of the direction of the signal, in relation to the CNS. On this basis, there are three different types of neurons: sensory neurons, motor neurons, and interneurons (Fig. 11.2).

Sensory neurons: Sensory neurons or afferent neurons carry input to the CNS for processing. They carry information from sensory receptors present in the skin or in the visceral organs to the CNS. They are mainly unipolar and have very long axons. The information from different sense organs, muscles, and other organs reaches the brain through the sensory neurons. The nerves associated with vision, hearing, taste, and smell are cranial nerves. They do not use the spinal cord. The nerves associated with touch (pressure, temperature, and pain) move through the spinal cord to reach the brain. So, sensory neurons are associated with the incoming of messages from the exter­nal environment as well as from the internal organs.

Motor neurons: Motor neurons or efferent neurons transmit the output of CNS to the periphery (to the muscles or glands). Motor neurons are mainly multipolar, and they carry signals from the CNS to the effectors present in muscles and tendons all over the body. They may be somatic or autonomic. Somatic neurons are again subdivided into upper motor and lower motor neurons. The autonomic neurons are divided into preganglionic and postganglionic neurons. So, the motor neurons are associated with the outgoing messages from the brain or spinal cord to act upon the outer environment as well as to different organs. Axons of motor neurons are generally long.

Interneurons: Interneurons remain in between two neurons and relay the information in between them with necessary modification. Interneurons may be inhibitory or excit­atory. Interneurons are small and have short axon. Most of the interneurons are located within the CNS. They are mainly present in the brain, spinal cord, and eye. The numbers of interneurons are higher than sensory or motor neurons.

11.1.1.3 Glial Cells or Neuroglia

Glial cells or neuroglia are supporting cells in the nervous system. They are not able to conduct nerve impulses. Their main functions are nourishment and protection of neurons. The number of glial cells is more than neurons, and they occupy half of the volume of the brain. Unlike neurons, glial

Fig. 11.2 Types of neuron. The figure depicts the afferent, efferent, and interneurons

Fig. 11.3 Different types of glial cells, their locations, and major functions

cells are capable of mitosis. Hence, glial cells can be replaced when damaged. Four types of glial cells are present in the CNS. These are astrocyte, oligodendrocyte, ependymal cells, and microglia (Fig. 11.3). In PNS, two types of glial cells are present, Schwann cell and satellite cell (Fig. 11.3).

11.1.1.3.1 GiiaiCeiisofCNS

1. Astrocyte: Astrocytes are star-shaped cells with multiple radiating cytoplasmic processes remaining in the CNS. Large number of processes wrap around the blood vessels and neurons. They have all the organelles of the somatic cell. Their position facilitates to control and adjust the extracellular environment around the neurons. Astrocytes are of two types, fibrous and protoplasmic. The former type has more fibrils, and the latter has more cytoplasm. The fibrous astrocytes are present in the white matter, while the protoplasmic astrocytes are present in the grey matter. Astrocytes attach their processes (foot process) to the capillaries and also to the neurons and synapses. They have a role in providing nutrition to the neurons and also contribute to blood-brain barrier. Astrocytes remove K⁺ and some neurotransmitters (GABA), which are liberated due to the actions of the neurons. Thus, astrocytes keep the vicinity of the neurons suitable for normal activity.

2. Oligodendrocytes: Oligodendrocytes are comparatively smaller and have less process than astrocytes. They form the myelin sheath in the nerve fibers in CNS; but, unlike the Schwann cells, they form the myelin sheath of many fibers at a time. It helps in the propagation of electrical impulses through the axon without being spread to other axons. They are also present in the grey matter around the cell bodies of the neurons. Oligodendrocytes wrap several times around a section of an axon. The intermittent gaps in the myelin sheaths of axons where the portion of axon is exposed are known as node of Ranvier. Myelination of nerve fibers increases the speed of nerve impulses through the axon. The propagation of action potentials through myelinated axons from one node of Ranvier to the next node increases the velocity of conduction of action potentials. It is called salutatory (Latin saltare, to hop or leap) conduction. Myelinations also bring about the clus­tering of voltage-gated Na⁺ channels at the nodes. Oligodendrocytes also help in the regulation of pH of the CNS.

3. Microglia: Microglia are small cells with long thin tortu­ous processes, which look like spines. These are believed to be derived from blood. These are phagocytic in function and are motile. Microglial cells are quickly activated in response to injury and infection or disease in CNS. These cells can proliferate and change shape. Microglial cells also play an important role in presenting the antigens to lymphocytes in response to any infection. Although these cells are an essential component of the CNS, it is believed that their activity is also toxic to neurons, causing long­term damage. As a result, medical intervention in response to brain injury often involves factors that inhibit microglial activity.

4. Ependymal cells: The lining cells of the ventricles of the brain and the central canal of spinal cord are called ependyma or ependymal cells. These cells are ciliated columnar type and are situated between brain extracellular fluid and cerebrospinal fluid (CSF). Thus, they form a blood-CSF barrier. They also line the outer surface of choroid capillaries, which are fenestrated, and the blood- CSF barrier is formed mainly by ependyma cells.

11.1.1.3.2 GiiaiCeiisofthePNS

1. Schwann cell: Schwann cells are the myelinating cells of the PNS. Unlike oligodendrocytes, a Schwann cell provides myelin sheath for a single segment of an axon; but the appearance and function of the myelin sheath in the PNS are just same as that of CNS.

2. Satellite cell: Satellite cells in the nervous system help in regulation of the external chemical environment around the neurons of the PNS. Satellite cells have functions very similar to the functions of astrocytes of the CNS. In addi­tion, they are very sensitive to injury and inflammation.

11.1.2 Synapse

The communication of neurons between each other and with other cells of the body, like muscle and glandular cells, occurs very fast, at specialized junctions called synapses (Greek, “junction” or “to bind tightly”). Synapse is also known as neuronal junction. The synaptic junction between a neuron and a muscle cell is called neuromuscular junction.

Structurally, two types of synapses are present in the body, the chemical synapse and electrical synapse. Both types of synapses help in the transmission of nerve impulse, but the mechanisms of transmission are different.

In electrical synapses, adjoining cell membranes are attached to each other and gap junctions appear as direct points of contact between the cytoplasm of adjacent neurons. Gap junctions permit the movement of ions from one cell to another. This type of synapses is found in cardiac muscle and single-unit smooth muscle.

In chemical synapses, cell membranes of the neurons adjoin very close to each other but remain distinct, leaving a space. In this type of synapses, neural communication occurs using chemical messengers, which are known as neurotransmitters. Neurotransmitter helps in the transmission of nerve impulses from one cell to another. Here, synapse is the junction between two nerve cells. Most of the synapses in the nervous system are chemical synapse. Discussion on the chemical synapse is emphasized in the chapter. The synapse is a site of attachment between a presynaptic element of one neuron and a postsynaptic membrane of another neuron (or an effector organ). The presynaptic axon enlargement releases neurotransmitter molecules, which diffuse across a synaptic cleft and bind to receptor present in the postsynaptic membrane.

11.1.2.1 Synaptic Anatomy

Generally, synapses are comprised of three major elements. These are the axon terminal or presynaptic nerve terminal. It transmits the information to the next part of the synapse, the synaptic cleft. The third element is the dendrite or postsynap- tic element, which receives the information.

1. Presynaptic nerve terminal: Presynaptic nerve terminal contains synaptic vesicles rich in neurotransmitter, which is released during the time of synaptic transmission. The vesicles fuse with the presynaptic membrane during syn­aptic transmission.

2. Synaptic cleft: It is the narrow gap between presynaptic and postsynaptic membranes into which neurotransmitter molecules are released.

3. Postsynaptic element: It receives the neurotransmitter. It may be a dendrite, a cell body, or a target cell receiving the synaptic input. The neurotransmitter molecules bind with the receptor protein molecules, which are embedded in the postsynaptic plasma membrane.

11.1.2.2 Classification of Synapse

The synapse is classified into four types according to the part of the neurons that are involved in the synapse. These are axodendritic, axosomatic, axoaxonic, and dendrodendritic.

1. Axodendritic: Synapse having the axon of one neuron attaching with the dendrite of another neuron is called axodendritic synapse.

2. Axosomatic: The axon of one neuron attaching with cell body or soma of another neuron forms axosomatic synapse.

3. Axoaxonic: Two axons attaching with each other form the axoaxonic synapse.

4. Dendrodendritic: Dendrites of two nerve cells attaching with each other form dendrodendritic synapse.

11.1.2.3 Synaptic Transmission

When an action potential travels through the axon and reaches the axon terminal, the adjacent presynaptic mem­brane becomes passively depolarized (toward zero trans­membrane potential). Then voltage-gated Ca²⁺ channels open. The Ca²⁺ enters the presynaptic neuron and signals to neurotransmitter vesicles (Fig. 11.4).

Neurotransmitter molecules are released in proportion to the amount of Ca²⁺ influx. The Ca²⁺ influx is in turn propor­tional to the amount of presynaptic membrane depolarization. The elevated Ca²⁺ causes mobilization of synaptic vesicles contacting neurotransmitter and docking of the vesicles with the plasma membrane. A number of synaptic vesicles fuse with presynaptic membrane, which results in the release of neurotransmitter molecules in the synaptic cleft via exocyto- sis. The neurotransmitter molecules then diffuse across the

Fig. 11.4 Synaptic transmission. (1) Axon potential arrives at the axon terminal, (2) voltage-gated Ca²+ channels open, (3) Ca²+ enters the presynaptic neuron,

(4) Ca²+ signals to neurotransmitter vesicles,

(5) vesicles move to the membrane and dock,

(6) neurotransmitters released via exocytosis, (7) neurotransmitters bind to receptors, (8) signal initiated in postsynaptic cell

synaptic cleft and ultimately bind with receptor proteins on postsynaptic membrane. Then the signal is initiated in post- synaptic cell. After the work is over, the neurotransmitter molecules are eliminated from synaptic clefts via pinocytotic uptake by presynaptic or glial processes and/or via enzymatic degradation at the postsynaptic membrane. The neurotrans­mitter molecules are recycled and subsequently presynaptic plasma membrane repolarizes (due to K⁺ channel conductance).

When neurotransmitter binds with the postsynaptic mem­brane, a proportional ion flux across the postsynaptic mem­brane occurs. The excitability effect depends on the nature of the ion flux. The ion flux depends on the nature of the ion channels in the particular postsynaptic membrane. In the resting state, postsynaptic plasma membrane remains polarized and at that time voltage-activated K⁺ channels dominate conductance.

When neurotransmitter molecules bind to ligand-gated receptors, which opens ion channels directly or by means of second messengers activation of [Na+ and K+] channels that leads to depolarization toward zero potential and activation of Cl^- or K+ channels. This results in hyperpolarization of postsynaptic membrane. A postsynaptic potential (PSP) occurs from the altered membrane conductance.

On the basis of the type of ion, the effect on the postsyn- aptic cell may be depolarizing (excitatory) or hyperpolarizing (inhibitory) and thus the excitatory response is known as excitatory postsynaptic potential (EPSP) and an inhibitory response is known as inhibitory postsynaptic potential (IPSP). From their names, it is clear that EPSP results in an excitatory response, or depolarization of membrane, and an IPSP elicit in an inhibitory response, or hyperpolarization of membrane.

EPSP and IPSP The cell body of neuron forms multiple synapses on it and on its dendrites. Within these synapses, some change the membrane potential of cell body nearer to threshold potential, whereas other synapses change mem­brane potential of the cell body moving further from thresh­old potential (hyperpolarization). The synapses which move membrane potential closer to threshold potential are known as excitatory postsynaptic potential, and the synapses which move the potential further from threshold are known as inhibitory postsynaptic potential. As a result, the net effect of all the EPSPs and IPSPs occurs at the axon hillock. If the potential reaches the threshold, then an action potential will generate and that will continue down the axon.

The aim of an EPSP is to initiate the change in the membrane to generate an action potential. On the other hand, the IPSP prevents the generation of an action potential. EPSP or IPSP lasts for a few milliseconds, and then the membrane returns to the original resting membrane potentials. Sometimes, a single EPSP is not sufficient to generate an action potential and then many EPSPs from different synapses combine at the cell body and result in much larger voltage change, which can exceed threshold potential and cause generation of action potential. This phe­nomenon is known as spatial summation. The combined phenomenon of occurrence of multiple EPSPs from the same synapse in rapid succession is known as temporal summation.

11.1.2.3.1 Summation

The generation of EPSP or IPSP depends on the type of neuron and their receptors. Receptors can be divided into two broad categories, the chemically gated ion channels and second messenger systems. After activation, chemically gated ion channels allow certain ions to move across the membrane. The type of ion will determine the generation of EPSP or IPSP. Activation of second messenger system results in a cascade of molecular interactions in the postsyn- aptic cell. The type of cascade which occurs will result in the response being either excitatory or inhibitory.

Excitatory Synapses: The neurotransmitters mostly used in excitatory synapses in the brain are glutamate or aspartate. They bind to nonselective cationic channels which allow for Na⁺ and K⁺ to pass. A number of EPSPs from these types of synapses cause the depolarization of postsynaptic neuron. When it reaches the threshold, the action potential is generated.

Inhibitory Synapses: Inhibitory neurotransmitters are essen­tial for controlling the excitability of neurons. This is regulated by a balance between excitation and inhibition. The major inhibitory neurotransmitters are GABA and glycine. They bind to their receptors resulting in an increased conductance of Cl^-. The negatively charged Cl^- that usually moves into the cell results in inhibition of depolarization and keeps the membrane to move away from threshold.

Modulatory Synapses: The activity of many synapses is influenced by neuromodulators. They are able to respond more powerfully to other inputs. For example, norepi­nephrine acts as a neuromodulator. Norepinephrine has little effect on synaptic transmission, but when a cell is exposed to norepinephrine first, it will react more power­fully to glutamate.

11.1.3 Neurotransmitter

Neurotransmitters are the chemical transmitter or chemical messenger substances liberated at the nerve endings and help to transfer nerve impulses in the presynaptic neuron to an adjacent cell (neighboring postsynaptic neurons or muscle or gland cells). They are endogenous chemical messengers that help in communication within the nervous system as well as between the nervous system and the rest of the body. Synapses relay information between the neurons and ulti­mately regulate a wide range of bodily functions.

Different types of neurotransmitters with different functions and mechanisms of action are present in the ner­vous system. Their levels and function are very important for maintaining the homeostasis, and any alteration in their levels or functions can lead to diseases. Chemicals secreted by neurons enter in blood to act as hormones, which are often called neurohormones. ADH and GnRH are neurohormones.

11.1.3.1 Characteristics of Neurotransmitter

A chemical to be liberated as a neurotransmitter should have the following criteria:

1. The chemical must be synthesized in the neuron concerned.

2. It should be stored in the presynaptic terminal.

3. It should be released at the synapse in amounts sufficient to exert a defined action.

4. It should have its specific receptors on postsynaptic membrane.

5. It should be removed quickly by the specific mechanism as soon its action is over.

The chemicals which are secreted from the nerve endings on the target organ or into the ECF are called neurosecretion. Chemicals liberated at the neuromuscular junction are also called neurotransmitters. Another term neuromodulator is used to name the chemicals which are used to modify the activities of postsynaptic neuron.

11.1.3.2 Mechanism of Action of Neurotransmitter

Neurotransmitters transmit signals through the synapse at various locations, such as from one neuron to another neuron, at the neuromuscular junction (NMJ) like a target muscle cell or a gland.

Generally, neurotransmitter releases at a low (basal) level without any stimulation. The level increases in response to threshold action potentials. The binding of neurotransmitters to the postsynaptic membrane results in either excitation or inhibition depending on the neurotransmitter and the binding receptor. Details of mechanism of action have been explained in Sect. 11.1.2.3 and in Fig. 11.4 of this chapter.

11.1.3.3 Classification of Neurotransmitter

There are hundreds of neurotransmitters, but they can be grouped into certain classes depending on their structure and function.

On the basis of structure, neurotransmitters can be classed as follows:

1. Monoamines: The dopamine, noradrenaline, adrenaline, histamine, and serotonin belong to monoamine group.

2. Amino acids: The glutamate, gamma-aminobutyric acid (GABA), glycine, aspartate, and D-serine are in amino acid group.

3. Peptides: The opioids, endorphins, somatostatin, oxyto­cin, and vasopressin are differentiated as peptide group.

4. Other. The acetylcholine (ACh), adenosine, and nitric oxide are considered in the other group of neurotransmitter.

Neurotransmitters and neuromodulators can also be clas­sified into two main categories, as small-molecule transmitters and large-molecule transmitters. Small­molecule transmitters include monoamines, catecholamines, and amino acids. Large-molecule transmitters include a large number of peptides called neuropeptides including substance P, enkephalin, vasopressin, and a host of others.

Some other substances are also released in the synaptic cleft, which acts as either a transmitter or a modulator during synaptic transmission. The purine derivatives, like adenosine and adenosine triphosphate (ATP), and a gaseous molecule, like nitric oxide (NO), are examples of such substances.

Neurotransmitters can be classified on the basis of their function.

1. Excitatory neurotransmitters: This type of neurotransmit­ter increases the electrical excitability on the postsynaptic side through modulation of the transmembrane ion flow to facilitate transmission of an action potential.

2. Inhibitory neurotransmitters: This type of neurotransmit­ter decreases electrical excitability on the postsynaptic side to prevent the propagation of an action potential.

3. Neuromodulators: The neurotransmitters which can alter the strength of transmission between neurons by altering the amount of production and release of it are considered as neuromodulators.

11.1.3.3.1 Neurotransmitters in the Central Nervous System

A number of neurotransmitters act in the central nervous system (CNS), like ACh, amines, serotonin, dopamine, nor­epinephrine, epinephrine, glutamate, aspartate, glycine, γ-aminobutyric acid (GABA), peptides, and nitric oxide. Ace­tylcholine is synthesized from choline and acetyl coenzyme A (acetyl-CoA) in the axon terminal. Neurons that release ACh are called cholinergic neurons. The amine neurotransmitters (like dopamine, norepinephrine, epinephrine, serotonin, hista­mine, tyrosine) are derived from amino acids. Dopamine, norepinephrine, and epinephrine are synthesized from tyro­sine. Neurons that release norepinephrine or epinephrine are called adrenergic neurons. Serotonin (or 5-hydroxytryptamine or 5-HT) is derived from the amino acid tryptophan and histamine from histidine. Glutamate and aspartate are the excitatory neurotransmitters of the CNS.

The primary inhibitory neurotransmitters in the CNS are GABA and glycine. Peptides that act as neurotransmitters include substance P and opioid peptides such as enkephalins and endorphins. Substance P is involved in pain pathways, and enkephalins and endorphins mediate analgesia.

An unusual neurotransmitter, nitric oxide (NO), diffuses freely into the target neuron to bind to intracellular proteins. Nitric oxide is synthesized from oxygen and the amino acid arginine.

11.1.3.3.2 Neurotransmitters in the Peripheral Nervous System (PNS)

The neurotransmitters present in the peripheral nervous sys­tem (PNS) are acetylcholine (ACh), norepinephrine, and epinephrine.

11.1.3.4 Fate of Neurotransmitter

The neurotransmitters are detached from their receptors and are removed very fast from the synaptic cleft immediately after the completion of its action.

There are two processes for removal of the neurotransmitters after their action. These are the following:

(1) Enzymatic inactivation in the synaptic cleft and (2) dif­fusion away from the synaptic cleft.

1. Enzymatic inactivation: In this process, the neurotrans­mitter is inactivated by a specific enzyme in the synaptic cleft. The uptake constituents occur by the presynaptic terminal used for resynthesis of neurotransmitter.

Example: ACh quickly detaches after the action is over and is broken down into choline and acetate by the enzyme acetylcholinesterase (AChE), which is present on the postsynaptic membrane. Then choline is actively transported back into the presynaptic terminal for resynthesis.

2. Diffusion: In this process, neurotransmitters enter the circulation or are transported back into the neuron or into astrocytes.

Example: Glutamate is transported back into the presyn- aptic terminal or astrocytes after the completion of its work at synapse. Glutamate is repackaged into synaptic vesicles in the presynaptic terminal. In the astrocytes, glutamine synthetase acts on glutamate to convert it into glutamine, which is then transported back to the presyn- aptic terminal by glutamine transporters. Then it is repackaged into synaptic vesicles and used as neurotrans­mitter again.

Any abnormality in the release of neurotransmitters and their activity results in various neurological disorders and diseases. In schizophrenia, dysfunction of dopamine, gluta­mate, and GABA has been reported, whereas reductions in levels as well as activities of norepinephrine and serotonin have been reported in persons with depression. In Parkinson’s disease, decreased levels of dopamine have been reported due to the loss of so-called dopaminergic neurons.

11.2