The Neuron神经元
The neuron is the structural and functional unit of the nervous system
The human nervous system contains more than 10 billion neurons.Although neurons show the greatest variation in size and shape of any group of cells in the body，they fall into three general categories:
·Sensory neurons convey impulses from receptors to the CNS.Processes of these neurons are included in somatic afferent and visceral afferent nerve fibers.Somatic afferent fibers convey sensations of pain,temperature,touch,and pressure from the body surface.In addition，these fibers convey pain and proprioception(nonconscious sensation)from organs within the body(e.g.，muscles，tendons，and joints)to provide the brain with information related to the orientation of the body and limbs.Visceral afferent fibers transmit impulses of pain and other sensations from mucous membranes,glands,and blood vessels.
·Motor neurons convey impulses from the CNS or ganglia to effector cells.Processes of these neurons are included in somatic e fferent and visceral e fferent nerve fibers.Somatic efferent neurons send voluntary impulses to skeletal muscles.Visceral efferent neurons transmit involuntary impulses to smooth muscle，cardiac conducting cells(Purkinje fibers)，and glands(Fig.1).
·Interneurons,also called intercalated neurons,form a communicating and integrating network between the sensory and motor neurons.It is estimated that more than 99.9% of all neurons belong to this integrating network.
The functional components of a neuron include the cell body，axon，dendrites，and synaptic junctions
Fig.1 Diagram of a motor neuron.
The nerve cell body，dendrites，and initial part of the axon are within the CNS.The axon leaves the CNS and，while in the PNS，is part of a nerve(not shown)as courses to its effectors(striated muscle).In the CNS，the myelin for the axon is produced by，and is part of，an oligodendrocyte；in the PNS，the myelin is produced by，and is part of，a Schwann cell.(Adapted from Junqueira LC，Carneiro J，Kelley RO.Basic Histology，9th Norwalk，CT:Appleton & Lange，1998.)
The cell body(perikaryon)of a neuron contains the nucleus and those organelles that maintain the cell.The processes extending from the cell body constitute the single common structural characteristic of all neurons.Most neurons have only one axon,usually the longest process extending from the cell，which transmits impulses away from the cell body to a specialized terminal(synapse)，that makes contact with another neuron or an effector cell(e.g.，a muscle cell or glandular epithelial cell).A neuron usually has many dendrites,shorter processes that transmit impulses from the periphery(i.e.，other neurons)toward the cell body.
Neurons are classified on the basis of the number of processes extending from the cell body(Fig.2):
·Multipolar neurons have one axon and two or more dendrites.
·Bipolar neurons have one axon and one dendrite.
·Unipolar(actually pseudounipolar)neurons have one process,the axon,which divides close to the cell body into two long processes.The vast majority of unipolar neurons are located in the dorsal root ganglia and cranial nerve ganglia.
Motor neurons and interneurons are multipolar
Fig.2 Diagram illustrating different types of neurons.
The cell bodies of pseudounipolar(unipolar),bipolar,and postsynaptic autonomic neurons are located outside the CNS.Integrative neurons are restricted to the CNS；many of them have elaborate dendritic arborizations that facilitate their identification.a，axon.
Interneurons constitute most of the neurons in the nervous system.The direction of impulses is from dendrite to cell body to axon or from cell body to axon.Thus，functionally,dendrites and cell body of multipolar neurons are the receptor portions of the cell，and their plasma membrane is specially adapted for impulse generation.The axon is the conduct portion of the cell,and its plasma membrane is specialized impulse conduction.The terminal portion of the axon，synaptic ending，contains various neurotransmitters，i.e.，small molecules whose release at the synapse affects a neurons as well as muscle cells and glandular epithelium.
Sensory neurons are unipolar
The cell body of a sensory neuron is situated in a dorsal ganglion close to the CNS(Fig.3)；one axonal branch extends to the periphery，and one extends to the CNS.The two axonal branches are the conducting units.Functions impulses are generated in the peripheral arborizations(branches)of the neuron; these arborizations are the reception of the cell.Unipolar neurons are also sometimes called pseudounipolar because during development they exist as bipolar neurons.They become unipolar as their processes migrate around the cell body and fuse into a single process as the cell matures.
True bipolar neurons are limited to the retina of the eye and the ganglia of the vestibulocochlear nerve(cranial nerve VIII)of the ear
Neurons associated with the receptors for the special senses(taste，smell，hearing，sight，and equilibrium)often do not fit the above generalizations.For example,the amacrine cells of the retina have no axons,and the olfactory receptors resemble neurons of primitive neural systems,in that they retain a surface location and remain a slowly renewing cell population.
Cell Body
The cell body of a neuron has characteristics of a proteinproducing cell
The cell body is the dilated region of the neuron that contains a large,euchromatic nucleus with a prominent nucleolus and surrounding perinuclear cytoplasm.The perinuclear cytoplasm reveals abundant rough endoplasmic reticulum(rER)and free ribosomes when observe with the transmission electron microscope(TEM)，a feature consistent with its protein synthetic activity.In the light microscope the ribosomal content appears as small bodies,called Nissi bodies,those stain intensely with basic dyes and metachromatically with thionine dyes(Fig.4).Each Nissl body corresponds to a stack of rER.The perinuclear cytoplasm also contains numerous mitochondria,a large perinuclear Golgi apparatus,lysosomes,microtubules,neurofilaments(intermediate filaments)，transport vesicles，and inclusions(Fig.5).Nissl bodies,free ribosomes,and,occasionally,the Golgi apparatus extend into the dendrites but not into the axon.This area of the cell body，called the axon hillock,is free of large cytoplasmic organelles and serves as a landmark to distinguish between axons and dendrites in both light microscope and TEM preparations.
Fig.3 Schematic diagram showing arrangement of motor and sensory neurons.
The cell body of a motor neuron is located in ventral(anterior)horn of the gray matter of the spinal cord.Its axon，surrounded by myelin，leaves the spinal cord via a ventral(anterior)and becomes part of a spinal nerve that carries it to its destination on striated(skeletal)muscle fibers.The sensory neuron originates in there within a receptor(here，a Pacinian corpuscle)and continues as a component of a spinal nerve,entering the spinal cord via the dorsal(posterior root.Note the location of its cell body in the dorsal root ganglion(sensory ganglion).A segment of the spinal nerve is enlarged to show there lationship of the nerve fibers to the surrounding connective tissue(endoneurium，perineurium，and epineurium).In addition，segments of sensory and motor neurons have been enlarged to show the relationship of the axons to the Schwann cells and myelin.(Autonomic nerve fibres are not shown in the diagram.)
Fig.4 Photomicrograph of nerve cell bodies.
This photomicrograph shows a region of the ventral(anterior)horn of a human spinal cord stained with toluidine blue.Typical features of the nerve cell bodies visible in this photomicrograph include large，spherical，pale-stained nuclei with a single prominent nucleolus and abundant Nissi bodies within the cytoplasm of the nerve cell body.Most of the small nuclei belong to neuroglial cells.The remainder of the field consists of nerve fibers and cytoplasm of neuroglial cells.x640.
The euchromatic nucleus,large nucleolus,prominent Golgi apparatus,and Nissl substance indicate the high level of anabolic activity needed to maintain these large cells.
Neurons do not divide；however，in some areas of the brain neural stem cells are present and are able to differentiate and replace damaged nerve cells
Although neurons do not replicate,the subcellular components of the neurons turn over regularly and have life spans measured in hours,days,and weeks.The constant need to replace enzymes，neurotransmitter substances，membrane components，and other complex molecules is consistent with the morphologic features characteristic of a high level of synthetic activity.Newly synthesized protein molecules are transported to distant locations within a neuron in a process referred to as axonal transport.
Fig.5 Electron micrograph of a nerve cell body.
The cytoplasm is occupied by aggregates of free ribosomes and profiles of rough endoplasmic reticulum(rER)that constitute the Nissl bodies of light microscopy.The Golgi apparatus(G)ap-pears as isolated areas containing profiles of flattened sacs and vesicles.Other cha-racteristic organelles include mitochondria(M)and lysosomes(L).The neurofilaments and microtubules are difficult to discern at this relatively low magnification.x15，000.
It is generally accepted that nerve cells do not divide.However，recently it has been shown that the adult brain retains some cells that exhibit the potential to regenerate and satisfy the criteria of being neural stem cells.In certain regions of the brain，these cells are able to divide and generate new neurons.These neural stem cells are also able to migrate sites of injury and differentiate into new nerve cells.These findings may lead to therapeutic strategies that use neural cells to replace nerve cells lost or damaged by neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.
Dendrites and Axons
Dendrites are receptor processes that receive stimuli from other neurons or from the external environment
The main function of dendrites is to receive information from other neurons or from the external environment and carry that information to the cell body.Generally，dendrites are located in the vicinity of the cell body.They have a greater diameter than axons,are unmyelinated,are usually tapered,and form extensive arborizations called dendritic trees.Dendritic trees significantly increase the receptor surface area of a neuron.Many neuron types are characterized by the extent and shape of their dendritic trees(see Fig.2).In general，the contents of the cell body and dendrites are similar，with the exception of the Golgi apparatus.Whereas the Golgi network remains close to the nucleus，other organelles characteristic of the cell body proper,including ribosomes and rER,are found in the dendrites，especially in the base of the dendrites.
Axons are effector processes that transmit stimuli to other neurons or effector cells
The main function of the axon is to convey information away from the cell body to another neuron or to an effector cell，such as a muscle cell.Each neuron has only one axon，and it may be extremely long.Axons that originate from neurons in the motor nuclei of the CNS(Golgi type I ne urons)may travel more than a meter to reach their effector targets，skeletal muscle.In contrast，interneurons of the CNS(Golgi type II neurons)have a very short axon.Although an axon may give rise to a recurrent branch near the cell body(i.e.，one that turns back toward the cell body；see Fig.1)and to other collateral branches，the branching of the axon is most extensive in the vicinity of its targets.
The axon originates from the axon hillock.As mentioned，it usually lacks large cytoplasmic organelles such as Nissi bodies and Golgi cisternae.Microtubules，neurofilaments，mitochondria，and vesicles，however，pass through the axon hillock into the axon.The region of the axon between the apex of the axon hillock and the beginning of the myelin sheath(see below)is called the initial segment.The initial segment is the site at which an action potential is generated in the axon.The action potential(described in more detail below)is stimulated by impulses carried to the axon hillock on the membrane of the cell body after other impulses are received on the dendrites or the cell body itself.
Some large axon terminals are capable of local protein thesis，which may be involved in memory processes
Almost all of the structural and functional protein molecules are synthesized in the nerve cell body.These molecules are contributed to the axons and dendrites via axonal transport systems.However，contrary to the common view that the nerve cell body is the only site of protein synthesis,recent studies provide evidence of local thesis of axonal proteins in some large nerve terminals.Some vertebral axon terminals(i.e.，from the retina)contain polyribosomes with complete translational machinery for protein synthesis.These discrete areas within the axon terminals，called periaxoplasmic plaques,possess biochemical molecular characteristics of active protein synthesis.Protein synthesis within the periaxoplasmic plaques is modulated by neuronal activity.These proteins may be involved in the processes of neuronal cell memory.
Clinical Correlation:Parkinson’s Disease
Parkinson’ disease is a slowly progressive neurologic disorder caused by the loss of dopamine(DA)-secreting cells in the substantia nigra and basal ganglia of the brain.DA is a neurotransmitter responsible for synaptic transmission in the nerve pathways coordinating smooth and focused activity of skeletal muscles.Loss of DA-secreting cells is associated with a classic pattern of symptoms，including
·Resting tremor in the limb，especially of the hand when in a relaxed position; tremor usually increases during stress and is often more severe on one side of the body
·Rigidity or increased tone(stiffness)in all muscles
·Slowness of movement(bradykinesia)and inability to initiate movement(akinesia)
·Lack of spontaneous movements
·Loss of postural reflexes，which leads to poor balance and abnormal walking(festinating gait)
·Slurred speech，slowness of thought，and small，cramped handwriting
The cause of idiopathic Parkinson’s disease，in which DA-secreting neurons in the substantia nigra are damaged and lost by degeneration or apoptosis,is not known.However，some evidence suggests a hereditary predisposition；about 20% of Parkinson’s patients have a family member with similar symptoms.
Symptoms that resemble idiopathic Parkinson’s disease may also result from infections(e.g.，encephalitis)，toxins(e.g.，MPTP)，drugs used in the treatment of neurologic disorders(e.g.，neuroleptics used to treat schizophrenia)，and repetitive trauma.Symptoms with these causes are called secondary parkinsonism.
On the microscopic level,degeneration of neurons in the substantia nigra is very evident.This region loses its typical pigmentation，and an increase in the number of glial cells is noticeable(gliosis).In addition，nerve cells in this region display characteristic intracellular inclusions called Lewy bodies，which represent accumulation of intermediate neurofilaments in association with proteins a-synuclein and ubiquitin.
Treatment of Parkinson’s disease is primarily symptomatic and must strike a balance between relieving symptoms and minimizing psychotic side effects.L-Dopa is a precursor of DA that can cross the blood—brain barrier and is then converted to DA.It is often the primary agent used to treat Parkinson’s disease.Other drugs that are used include a group of cholinergic receptor blockers and amantadine，a drug that stimulates release of DA from neurons.(https://www.daowen.com)
If drug therapies are not effective，several surgical options can be considered.Stereotactic surgery，in which nuclei in selective areas of the brain(globus pallidus,thalamus)are destroyed by a thermocoagulative probe inserted into the brain，can be effective in some cases.Several new surgical procedures are being developed and are still in experimental stages.These include transplantation of DA-secreting neurons into the substantia nigra to replace lost neurons.
Synapses
Neurons communicate with other neurons and with effector cells by synapses
Synapses are specialized junctions between neurons that facilitate transmission of impulses from one(presynaptic)neuron to another(postsynaptic)neuron.Synapses also occur between axons and effector(target)cells，such as muscle and gland cells.Synapses between neurons may be classified morphologically as
·Axodendritic，occurring between axons and dendrites
·Axosomatic，occurring between axons and the cell body
·Axosomatic，occurring between axons and axons(Fig.6)
Synapses are not resolvable in routine hematoxylin and eosin(H&E)preparations.However，silver precipitation staining methods(e.g.，Golgi method)not only demonstrate the overall shape of some neurons but also show synapses as oval bodies on the surface of the receptor neuron(Fig 7).Typically，an axon makes several of these buttonlike contacts with the receptor portion of the neuron.Often，the incoming neuron travels along the surface of the neuron，making several synaptic contacts called boutons en passant(Fr.，buttons in passing).The axon then continues，to end finally as a terminal twig with an enlarged tip，a bouton terminal(Fr.，terminal button),or end bulb.The number of synapses on a neuron or its processes，which may vary from a few to tens of thousands per neuron,appears to be directly related to the number of impulses that a neuron is receiving and processing.
Fig.6 Schematic diagram of different types of synapses.
a.Axodendritic or axosomatic.b.Axodendritic，in which an axon terminal synapses with a dendritic spine.c.Axoaxonic.The axoaxonic synapse may enhance or inhibit the axodendritic(or axosomatic)synapse.(Modified Barr ML.The Human Nervous System.New York；Harper & Row，1979.)
Synapses are classified as chemical or electrical
Classification depends on the mechanism of conduction of the nerve impulses and the way the action potential is generated in the target cells.Synapses may also be classified as
·Chemical synapses，in which conduction of impulses is achieved by the release of chemical substances(neuro-transmitters)from the presynaptic neuron.Neurotransmitters then diffuse across the narrow intercellular space that separates a presynaptic neuron from a postsynaptic neuron or target cell.
·Electrical synapses，which are common in invertebrates，contain gap junctions that permit movement of ions between cells and consequently permit the direct spread of electrical current from one cell to another.These synapses do not require neurotransmitters for their function.Mammalian equivalents of electrical synapses include gap junctions in smooth muscle and cardiac muscle cells.
Fig.7 Representation of a neuron cell body in the CNS.
A.This drawing illustrates the cell body of a neuron.Axon endings forming synapses are shown as the numerous ovoid bodies with taillike appendages.Each represents an axon terminal from a different neuron making contact with the cell body or its dendrites.b.The axon ending within the rectangle in a has been enlarged，illustrating its appearance with the transmission electron microscope，which reveals significant structural features.(Reprinted with permission from DeRobertis EDP，Nowinsky WW，Saez FA.Biologia Celular.Buenos Aires:El Ateneo，1970.)
A typical chemical synapse contains a presynaptic knob，synaptic cleft，and postsynaptic membrane
Components of a typical chemical synapse include
·Presynaptic knob(presynaptic component),the end of the neuron process from which neurotransmitters are released.The presynaptic component，i.e.，the bouton terminal，is characterized by the presence of synaptic vesicles，membrane-limited structures that range from 30 to 100 nm in diameter and contain neurotransmitters(Fig 8).A specific ATP-binding protein called N-ethylmaleimide-sensitive factor(NSF)found on the membrane of synaptic vesicles is required for formation，targeting，and fusion of these vesicles with the presynaptic membrane.Numerous small mitochondria and a layer of dense material,the presynaptic den sity,are present on the cytoplasmic side of the plasma membrane.
Fig.8 Diagram of a chemical axodendritic synapse.
This diagram illustrates three components of a typical synapse.(1)The presynaptic knob is located at the distal end of the axon from which neurotransmitters are released.The presynaptic knob is characterized by the presence of numerous neurotransmitter-containing synaptic vesicles.Synaptic vesicles contain N-ethylmaleimide-sensitive factor(NSF)on their membrane；NSF is required for vesicle formation，targeting，and fusion with the presynaptic membrane.The plasma membrane of the presynaptic knob is recycled by the formation of clathrin-coated endocytotic vesicles.(2)The synaptic cleft separates the presynaptic knob of the axon from the postsynaptic membrane of the dendrite.(3)The postsynaptic membrane of the dendrite is frequently characterized by a postsynaptic density and contains receptors with an affinity for the neurotransmitters.a.Diagram showing the current view of neurotransmitter release from presynaptic knob by a fusion of the synaptic vesicles with presynaptic membrane.b.Diagram showing a new proposed model of the neurotransmitter release via pinocytosis.In this model the synaptic vesicle is anchored and juxtaposed to calcium-selective channels in the presynaptic membrane.In the presence of Ca2+ the bilayers of the vesicle and presynaptic membranes are reorganized to create a 1-nm transient pore connecting the lumen of the vesicle with the synaptic cleft allowing the release of neurotransmitter.
·Synaptic cleft,the 20-to 30-nm space that separates the presynaptic neuron from the postsynaptic neuron or target cell，which the neurotransmitter must cross.
·Postsynaptic membrane(postsynaptic component)，which contains receptor sites with which the neurotransmitter interacts.This component is formed from a portion of the plasma membrane of the postsynaptic neuron(Fig 9)and is characterized by a layer of dense material,the postsynaptic density,on the cytoplasmic side of the membrane.
Synaptic Transmission
Voltage-gated Ca2+ channels in the membrane of the bouton regulate transmitter release
When a nerve impulse reaches the bouton,the voltage reversal across the membrane produced by the impulse(called depolarization)causes Voltagegated Ca2+ channels to open in the plasma membrane of the bouton.The influx of Ca2+ from the extracellular space causes the synaptic vesicles to migrate to,and fuse with，the presynaptic membrane，thereby releasing the neurotransmitter into the synaptic cleft by exocytosis or pinocytosis.The neuro-transmitter then diffuses across the synaptic cleft.At the same time，the presynaptic membrane of the bouton that released the neurotransmitter quickly forms endocytotic vesicles that return to the endosomal compartment of the bouton for reloading with neurotransmitter.Meanwhile，specific receptors on the postsynaptic membrane bind neurotransmitter,causing ligand-gated Na+ channels in that membrane to open，allowing Na+ to enter the neuron.This ion flux causes local depolarization in the postsynaptic membrane，which in turn，under favorable conditions(sufficient amount and duration of neurotransmitter release),can cause voltagegated Na+ channels that are present in the same area to open,thereby generating a nerve impulse.The firing of impulses in the postsynaptic neuron is caused by the summated action of hundreds of synapses.
The chemical nature of the neurotransmitter determines the type of response at that synapse in the generation of neuronal impulses
The release of neurotransmitter by the presynaptic component can cause either excitation or inhibition at the postsynaptic membrane.
·In excitatory synapses,release of neurotransmitters such as acetylcholine，glutamine,or serotonin opens cation channels，prompting an influx of Na+ that causes local reversal of voltage of the postsynaptic membrane to a threshold level(depolarization).This leads to initiation of an action potential and generation of a nerve impulse.
Fig.9 Electron micrograph of nerve processes in the cerebral cortex.
A synapse can be seen in the center of the micrograph，where an axon ending is apposed to a dendrite.The ending of the axon exhibits numerous neurotransmitter-containing synaptic vesicles that appear as circular profiles.The postsynaptic membrane of the dendrite shows a postsynaptic density.A substance of similar density is also present in the synaptic cleft(intercellular space)at the synapse.X76，000.(Courtesy of Drs.George D.Pappas and Virginia Kriho.)
·In inhibitory synapses,release of neurotransmitters such as g-aminobutyric acid(GABA)or glycine,opens anion channels,causing Cl-to enter the cell and hyperpolarize the postsynaptic membrane，making it even more negative.In these synapses，the generation of an action potential then becomes more difficult.
The ultimate generation of a nerve impulse in a postsynaptic neuron(firing)depends on the summation of excitatory and inhibitory impulses reaching that neuron.This allows precise regulation of the reaction of a postsynaptic neuron(or muscle or gland cell).The function of synapses is not simply to transmit impulses in an unchanged manner from one neuron to another.Rather，synapses allow for the processing of neuronal input.Typically，the impulse passing from the presynaptic to the postsynaptic neuron is modified at the synapse by other neurons that，although not in the direct pathway，nevertheless have access to the synapse(see Fig.12.6).These other neurons may influence the membrane of the presynaptic neuron or the postsynaptic neuron and facilitate or inhibit the transmission of impulses.
Neurotransmitters
A number of molecules that serve as neurotransmitters have been identified in various parts of the nervous system.The most common neurotransmitters are
·Acetylcholine(ACh).ACh is the neurotransmitter between axons and striated muscle at the neuromuscular junction and serves as a neurotransmitter in the ANS.ACh is released by the presynaptic sympathetic and parasympathetic neurons and their effectors.ACh is also secreted by postsynaptic parasympathetic neurons，as well as by a specific type of postsynaptic sympathetic neuron that innervates sweat glands.Neurons that use ACh as their neurotransmitter are called cholinergic neurons.The receptors for ACh in the postsynaptic membrane are known as cholinergic re ceptors and are divided into two classes on the basis of their interactions with muscarine，isolated from poisonous mushrooms(muscarinic ACh receptor),and nicotine,isolated from tobacco plants(nicotinic ACh receptor).Various drugs affect release of ACh into the synaptic cleft as well as affect its binding to its receptors.For instance，in botulism,the botulinum toxin produced by the bacteria that grow in improperly canned meat and vegetable products inhibits ACh release.Inhibition of ACh release leads to decreasing receptor stimulation，causing respiratory distress and other skeletal muscle paralysis.
·Catecholamines such as norepinephrine(NE)，epinephrine(EPI)，and dopamine(DA).These neurotransmitters are synthesized in a series of enzymatic reactions from the amino acid tyrosine.NE serves as a transmitter between postsynaptic sympathetic axons and effectors in the ANS.Neurons that use NE as their neurotransmitter are called adrenergic neurons.EPI is secreted by some cells in the CNS as well as the endocrine cells(chromaffin cells)of the adrenal medulla during the fight-or-flight response.Serotonin or 5-hydroxytryptamine(5-HT).Serotonin is formed by the hydroxylation and decarboxylation of tryptophan.It functions as a neurotransmitter in neurons of the CNS and enteric nervous system.Neurons that use serotonin as their neurotransmitter are called serotonergic.After the release of serotonin，a portion is recycled by reuptake into presynaptic serotonergic neurons.
·ϒ-Aminobutyrate(GABA)，gl utamate(GLU)，aspart ate(ASP)，and glycine(GLY).These amino acids also act neurotransmitters，mainly in the CNS.
Several small peptides also have been shown to act as synaptic transmitters.Among these are substance P(so named because it was originally found in a powder of acetone extracts of brain and intestine)，hypothalamic releasing hormones，enkephalins，vasoactive intestinal peptide(VIP)，cholecystokinin(CCK)，and neurotensin.Many of these same substances are synthesized and released by enteroendocrine cells of the intestinal tract.They may act immediately on neighboring cells(paracrine se cretion)or be carried in the bloodstream as hormones to act on distant target cells(endocrine secretion).They are also synthesized and released by endocrine organs and by the neurosecretory neurons of the hypothalamus.
Nitric o xide(NO)，a simple gas with free radical properties，also has been identified as a neurotransmitter.At low concentrations，NO carries nerve impulses from one neuron to another.Unlike other neurotransmitters，which are synthesized in the nerve cell body and stored in synaptic vesicles,NO is synthesized within the synapse and used immediately.It is postulated that excitatory neurotransmitter GLU induces a chain reaction in which NO synthase is activated to produce NO，which in turn diffuses from the presynaptic knob via the synaptic cleft and postsynaptic membrane to the adjacent cell,resulting ultimately in generation of an action potential.
Neurotransmitters released into the synaptic cleft may be degraded or recaptured
The most common process of removal of the neurotransmitter after its release into the synaptic cleft is called high affinity reuptake.About 80% of released neurotransmitters are removed by this mechanism.These and other transmitters are reincorporated into vesicles in the presynaptic component by endocytosis and are available for recycling.Enzymes associated with the postsynaptic membrane degrade the remaining 20% of neurotransmitters.For example,acetylcholinesterase(AChE)degrades ACh; catechol O-methyltransferase(COMT)as well as monoamine oxidase(MAO)rapidly degrade NE.Therapeutic substances that inhibit the action of MAO have been shown to have beneficial effects in the treatment of clinical depression.The degradation or recapture of neurotransmitters is necessary to limit the duration of stimulation of the postsynaptic membrane.
Normally,membrane added to the plasma membrane of the nerve ending by exocytosis when synaptic vesicles fuse with it is retrieved by endocytosis and is reprocessed into synaptic vesicles by the smooth endoplasmic reticulum(sER)located in the nerve ending.
Pinocytosis describes the secretion of neurotransmitter that does not involve the fusion of synaptic vesicles with the presynaptic membrane
The current view of neurotransmitter release involves the full of the synaptic vesicles with presynaptic membrane.In process the contents of the vesicle are released into the exlluiar space.Based on evaluation of physiologic data and structural organization of nerve synapses，a new model of action called pinocytosis has been proposed to explain the lated release of neurotransmitters.In this model secretion the vesicles occurs without fusion of the vesicle meet with the plasma membrane of the presynaptic.brane.Instead the synaptic vesicle is anchored to the synaptic membrane where it is juxtaposed to Ca2+ selected channels in the presynaptic membrane by SNARE protein the presence of Ca2+ the bilayers of the vesicle and synaptic membranes are reorganized to create a 1-nm transpore connecting the lumen of the vesicle with the synaptic cleft.This allows for controlled release of neurotransmitters through the membrane pores.
Axonal Transport Systems
Subtances needed in the axon and dendrites are synthesized the cell body and require transport to those sites
Most neurons in the body possess elaborate axonal and dendritic processes.Because the synthetic activity of the neuron is concentrated in the nerve cell body,axonal transport is required to convey newly synthesized material to the processes.Axonal transport is a bidirectional mechanism.It serve as a mode of intracellular communication,carrying molecules and information along the microtubules and intermediate filaments from the axon terminal to the nerve cell body and from the nerve cell body to the axon terminal.Axonal transport is described as
·Anterograde transport carries material from the nerve cell body to the periphery.Kinesin，a microtubule-associated motor protein that uses ATP，is involved in anterograde transport.
·Retrograde transport carries material from the axon terminal and the dendrites to the nerve cell body.This transport is mediated by another microtubule-associated motor protein,dynein.
The transport systems may also be distinguished by the rate at which substances are transported:
·A slow transport system conveys substances from the cell body to the terminal bouton at the speed of 0.2 to 4mm/day.It is only an anterograde transport system.Structural elements such as tubulin molecules(microtubule precursors)，actin molecules，and the proteins that form neurofilaments are carried from the nerve cell body by the slow transport system.So，too，are cytoplasmic matrix proteins，such as actin，calmodulin，and various metabolic enzymes.
·A fast transport system conveys substances in both directions at a rate of 20 to 400 mm/day.Thus，it is both an anterograde and a retrograde system.The fast anterograde transport system carries to the axon terminal different membrane-limited organelles,such as sER components,synaptic vesicles,and mitochondria，and low-molecular-weight materials such as sugars，amino acids，nucleotides，some neurotransmitters，and calcium.The fast retrograde transport system carries to the nerve cell body many of the same materials as well as proteins and other molecules endocytosed at the axon terminal.Fast transport in either direction requires Alp，which is used by microtubuleassociated motor proteins,and depends on the micro-tubule arrangement that extends from the nerve cell body to the termination of the axon.Retrograde transport is the pathway followed by toxins and viruses that enter the CNS at nerve endings.Retrograde transport of exogenous enzymes,such as horseradish peroxidase,and of radiolabeled or immunolabeled tracer materials is now used to trace neuronal pathways and to identify the nerve cell bodies related to specific nerve endings.
Dendritic transport appears to have the same characteristics and to serve the same functions for the dendrite as axonal transport does for the axon.