FUNCTIONS:  Communication- based upon fundamental attributes of the protoplasm:  Irritability- capacity to react to various physical and chemical

agents  Conductivity- ability to transmit the resulting excitation from one place to another  Provides the structural and chemical basis of conscious experience; furnishes the mechanism and regulation of behavior, and maintenance of personality.  Some nerve cells possess integrative endocrine secretory capabilities (e.g. ganglia of the adrenal medulla contain secretory catecholamines that are released into the bloodstream upon stimulation). COMPOSITION:  Functionally divided into somatic and autonomic parts, each with central and peripheral divisions.

1.Central Nervous System (CNS)- contains nerve cells of the brain & spinal cord together with supporting cells called neuroglia.  Collections of neuron cell bodies with their dendrites and proximal parts of axons constitute the gray matter; collections of mostly myelinated axons are called white matter. Localized groups of neuron cell bodies are termed nuclei. 2.Peripheral Nervous System (PNS)- comprises all nervous tissue outside of the brain and spinal cord; keeps other tissues in communication with the CNS; supporting tissue is areolar CT.  Collections of neuron cell bodies are called ganglia; collections of mostly myelinated axons are called peripheral nerves. The nerve fiber is a single axon in a peripheral nerve.

1.Somatic Nervous System- includes all nerve tissue except the ANS. It controls somatosensory perception (touch, heat, cold) and somatomotor or voluntary functions. Acetylcholine is the most common somatic neurotransmitter. 2.Autonomic Nervous System- controls involuntary visceral function, and has both motor and sensory pathways.  Each motor pathway consists of 2 neurons that synapse in a peripheral autonomic ganglion. The cell body of the 1st neuron (preganglionic motor neuron) is in the CNS; the cell body of the 2nd neuron (postganglionic motor neuron) is in the peripheral ganglion. Motor neurons conduct impulses from CNS to skeletal muscle only.  The sensory neurons of the ANS have cell bodies in craniospinal ganglia, and processes extend to the periphery. Sensory neurons convey information from cutaneous and special sense organs, body wall and limbs to the CNS.  Axons of autonomic ganglia terminate in visceral effectors, smooth muscle, heart muscle, and glandular epithelium.

The ANS is subdivided into 2 systems which usually have antagonistic effects when they innervate the same organ. 1. Sympathetic system- thoracolumbar motor pathways have preganglionic neurons with cell bodies in the spinal cord segments T1-L3. The postganglionic neurons have cell bodies located mainly in the sympathetic chain ganglia (close to the spinal column). The sensory neurons have cell bodies in the dorsal root ganglia and long dendrites that reach the periphery. Sensory neurons convey information from receptors in viscera to CNS. Motor neurons conduct impulses to smooth muscle, cardiac muscle and glands. 2. Parasympathetic- craniosacral motor pathways are classified into 2 divisions: a. Cranial division- has preganglionic neurons with cell bodies in nuclei of medulla and midbrain. Axons of these neurons leave the CNS through cranial nerves III, VII, IX and X. b. Sacral division- has preganglionic cell bodies in the intermediate gray matter of the sacral spinal cord segments and postganglionic cell bodies in intramural and other ganglia close to their site of action. The sensory neuron cell bodies are located in the sacral root ganglia and cranial ganglia.

 The neuron is the unit structure of the nervous system  All NS functions is accomplished by a single neuron interconnecting with other neurons.

 Consists of the cell body (soma, cyton or perikaryon) consisting of the nucleus, plasma membrane & cytoplasm, and a variable number of cytoplasmic processes: dendrites (collect incoming messages and carry them toward the soma, and axons (transmit messages to target cells).  The cell body is found only in the gray matter in the CNS; in the PNS, they are found in ganglia and in some sensory regions.

 It is surrounded by a thin plasma membrane with junctional complexes to maintain the position of neurons and stabilize relations of their processes.  The large, central, spherical, & vesicular nucleus typically has a single dark-staining nucleolus that gives it a fish-eye appearance.  A Barr body may be present as a nucleolar satellite.

 Nerve cells are related with each other through neuronal circuits formed by their processes; points of contact where they are functionally related are termed synapses.  Various sizes and complexities of these circuits interact to generate a neural function.

Organelles in the neuroplasm include: 1.Neurofibrils- slender, interlacing threads formed by intermediate neurofilaments; neurotubules are disposed in areas around the nucleus and continue into processes.  They distribute neurotransmitters from their sites of synthesis towards the processes.  In degenerative diseases, e.g. Alzheimers disease, the neurofibrillar proteins are modified that form characteristic lesions called neurofibrillary tangles, affecting neuronal transport. 2.Nissl (chromophilic) substance- basophilic masses composed of RNPs.  They are coarser in large motor nerves of CNS, smallest in sensory nerves of root ganglia, and intermediate in size in sympathetic ganglia.  They have a nutritive function; their amount is diminished by fatigue and nerve injury (chromatolysis) by recovered after a period of rest.

 Golgi apparatus appears as irregular, wavy strands interconnected with tubular ER elements; smaller mitochondria are numerous in terminal boutons, in nodes of Ranvier; centrosome is present only in young neurons since adult neurons do not proliferate.  Inclusions- pigment granules of melanin and lipofuscin, lipid droplets, iron granules all increase in amount as individual grows older; glycogen granules are found only in embryonal neurons and neuroglia.  Neurons may have one or more dendrites, which are short processes with a broad base; branches have surfaces covered with spines or gemmules that serve as sites of synaptic content.  They carry impulses toward the cell body (afferent).  They lack Golgi complexes, other organelles may be present, but these gradually disappear (except the mitochondria) towards termination.

 There is only 1 axon per neuron (except the amacrine retinal cells which have no axon) which is usually thinner and longer than dendrites of the same cell.  It arises from the axon hillock or implantation cone of the cell body; does not contain Nissl bodies; abundant neurofibrils are embedded in the axoplasm.  The absence of polyribosomes and rER emphasize dependence of the axon on the soma for its maintenance.

 It continues as the axis cylinder of the nerve fiber; the larger its diameter, the more likely it is to be myelinated.  In myelinated axons, the portion between the axon hillock and myelination is the initial segment where various excitatory and inhibitory stimuli become nerve impulses.  Branches of axons (collaterals) arise at right angles from nodes of Ranvier, ending in terminal arborizations (telodendria) at synapses.

Classification of By configuration of their cell processes: Neurons: 1. Unipolar- pyriform cells with a single short axon with no dendrite; rare, except in embryonic stages and in photoreceptor cells of retina. Spinal ganglion cells are considered pseudounipolar because they result from the fusion of axons and dendrites of bipolar embryonal neurons. 2. Bipolar- fusiform cells with a single dendrite and axon, e.g. retinal cells, vestibular & cochlear ganglia, olfactory cells of nasal epithelium. 3. Multipolar- the most abundant type; stellate cells with more than 2 processes; include motor nerves of ventral gray matter of the spinal cord, and motor nuclei of the brain stem.

By cell size:

 Golgi cell type I (Deiters cell or projection neurons)- with many dendrites and very long axons leaving the gray matter to become PNS nerve fibers; they form main fiber tracts of CNS, and conduct impulses over long distances.  Golgi cell type II (association neurons)- smaller cells with short axons that do not leave gray matter; numerous in cerebral and cerebellar cortices and retina.  Purkinje cells- big, pyriform bipolar cells in the middle of the cerebellar cortex with dendritic branching, and a long axon that enters the white matter.  Pyramidal cells- exceptionally large neurons, e.g. cells of Betz in mammalian cerebral cortex

By function: 1.Motor (efferent) neurons- carry nerve impulses to peripheral end organs and induce or inhibit muscular contraction, glandular secretion or both. 2.Sensory (afferent) neurons- receive impulses generated by the stimulation of peripheral sensory cells and carry them toward the CNS. There are 3 types: exteroreceptors near the body surface; interoreceptors in internal organs; proprioreceptors in muscles, tendons and joints. 3.Interneurons- have short processes and mediate interactions between: a sensory and a motor neuron (reflex actions); one motor neuron and another (concerted action of different muscle groups); or sensory neurons 4.By neurotransmitter released- neurons may be named as: cholinergic (acetylcholine); GABAergic (gamma aminobutyric acid); sympathetic postganglionic neurons are noradrenegic or adrenergic (noradrenalin or adrenalin); parasympathetic ganglionic neurons are cholinergic.

GANGLIA
 A ganglion is composed of nerve cells, and nerve fibers outside the CNS. It is termed a ganglion proper when nerve cells predominate nerve fibers; a plexus if it has fewer nerve cells and more nerve fibers.  Ganglia vary greatly in size; each has a CT capsule with blood vessels. Each ganglion cells has a capsule composed of a single layer of small, flattened satellite cells. Ganglia are classified into 2 types: 1. Cerebro or craniospinal ganglia- sensory cells are pseudounipolar (except bipolar cells of acoustic ganglion). Ganglion cells are covered with epithelioid capsule, and are associated with medullated or myelinated nerves with a neourolemma. Satellite glial cells are more numerous, have more spheric nuclei, and completely surround the soma of each ganglion cell. They are concentrated peripherally around the core of abundant processes; smaller nuclei belong to Schwann cells; no synapses in these ganglia.

2.Autonomic ganglia- appear as bulbous swellings in autonomic nerves.  The multipolar, stellate cells are smaller than those of the cerebrospinal ganglia; their satellite cells are less numerous, have more ovoid nuclei, and form a discontinuous sheath around the cell bodies.  Axons are unmyelinated, and do not form bundles.  Ganglion cells are mostly visceromotor neurons with both sympathetic (found closer to the CNS), and parasympathetic fibers (often found as intramural ganglia, where they are part of organs they supply)

SUPPORTING CELLS OF CNS

 Wherever nerve cell bodies and their processes are not in synaptic contact with another neuron, they are generally enveloped by neuroglia.

 They are involved in communication in the nervous system, a mediator for normal metabolism of neurons, are actively involved in the degeneration and regeneration of nerve fibers, defense processes, and are the chief source of tumors of the CNS. They are classified into: 1.Ependymal cells- found lining the ventricles of the brain and central canal of spinal cord where some ciliated forms facilitate the movement of cerebrospinal fluid.  In maturity, the broad bases of these previously embryonic cells taper to branching, threadlike processes forming the CNS limiting membranes.

2.Macroglia- ectodermal in origin  Astrocytes- biggest among glial cells; they are stellate cells with branching processes.  The neuropil constitute the processes of astrocytes and other glial elements lying between nerve cell bodies and their axons and dendrites.  Some processes of astrocytes have terminal expansions (perivascular or sucker foot, vascular end-feet) that contact blood vessels and serve as components of the blood-brain barrier.

 Astrocytes can also influence neuronal activity and survival through their ability to regulate constituents of the extracellular environment, absorb local excess of neurotransmitters, and release metabolic and neuroactive molecules: peptides of the angiotensin family, vasoactive endothelins, opioid precursors (enkephalins), and the potentially neurotrophic somatostatin.  Participate in brain development by assisting migration or neurons  Their processes provide link between neurons and blood vessels and form the blood-brain barrier (BBB) which regulate entry of substances into brain (allows diffusion only of lipid soluble substances: nicotine, ethanol, heroin; water soluble substances may pass but only by mediated transport: glucose, amino acids  By means of desmosomes, gap junctions and release of various cytokines, astrocytes communicate with other neurons or glial cells such as oligodendrocytes to influence myelin turnover in both normal and abnormal conditions.

3 types morphological types:  Protoplasmic astrocytefound mainly within the gray matter of the brain and spinal cord, adjacent to cell bodies. Granules along their processes have spheroidal swellings called gliosomes.  Fibrous astrocyte, spider cell or long-rayed astrocytesfewer processes appear longer, straight, with fewer branches; gliosomes and perivascular feet are also present; they are numerous in the white matter.  Mixed or plasmatofibrous- encountered at the boundary of gray and white matter; those entering the gray matter have protoplasmic character, while those entering the white matter are fibrous.

3.Oligodendrocytes or oligodendroglia- most numerous glial cell type. They are smaller cells with dark staining nucleus, scanty cytoplasm with very short processes having few branches. They show rhythmic pulsation in tissue culture.  Perineuronal satellitesurround nerve cells in the gray matter of CNS  Perivascular satellitetheir cell bodies and processes are attached intimately to the walls of blood vessels.

 Intrafascicular glia or sheath cellsrelate intimately to nerve fibers along which they form rows or columns in the white matter of the CNS.  They form the myelin in CNS; hence it is considered a homologue of the neurilemmal cell of Schwann.

4.Microglia or mesoglia- originate from precursor cells in the bone marrow.  Are small cells with dense elongated nuclei, and processes that are short and twisted, and covered with spines.  Scattered everywhere throughout the brain and spinal cord; they are also capable of amoeboid movement.  Are representative macrophages of the CNS in the mononuclear phagocyte system (in multiple sclerosis, microglia degrade the damaged myelin sheath).  Involved with inflammation and repair in the adult CNS, and secrete immunoregulatory cytokines (AIDS dementia complex is caused by HIV-1 infection of the CNS microglia.  Interleukin-1 and tumor necrosis factor-E activate and enhance HIV replication in microglia).

Photomicrographs (prepared with Golgi stain) of glial cells from the cerebral cortex. A: Fibrous astrocytes, showing blood vessels . B: Protoplasmic astrocyte showing brain surface (arrow). C: Microglial cell. D: Oligodendrocytes

SUPPORTING CELLS OF PNS

1.Schwann cells- supporting cells of the peripheral nerves. A myelinated axon is surrounded by multiple layers of a Schwann cell process with most of its cytoplasm squeezed out; the remaining multilayered Schwann cell plasma membrane, called myelin, is composed mainly of a phospholipid complex.

2.Satellite cells- specialized Schwann cells found in the dorsal root ganglia and autonomic ganglia of the PNS, where they form a 1-cell thick covering over the ganglion cells.  Their spherical nuclei typically appear as a string of pearls surrounding the much larger ganglion cell bodies.

Myelin sheath of the CNS. The same oligodendrocyte forms myelin sheaths for several (350) nerve fibers. In the CNS, processes of other cells sometimes cover the nodes of Ranvier, or there is considerable extracellular space (ES) at that point. The axolemma shows a thickening where the cell membrane of the oligodendrocyte comes into contact with it. This limits the diffusion of materials into the periaxonal space between the axon and the myelin sheath. At upper left is a surface view of the cell body of an oligodendrocyte.

N E R V E F I B E R S

 A nerve fiber refers to all nerve cell processes, particularly to long axons and their sheaths of ectodermal origin.  A nerve fiber may acquire coverings as it leaves the CNS: the neurolemma composed of Schwann cells; within this sheath forms the myelin sheath acquired by larger peripheral nerves.  Myelin or Medullary sheathlipoid substance that imparts the color of the white matter. In the CNS, this sheath is formed by interfascicular glia cells, while those in the PNS come from Schwann cells.  Sheath of Schwann or neurolemma- flat, nucleated, Schwann cells surround the myelin sheath, forming its superficial lamella. The cells may transform into phagocytes in tissue culture; in regeneration the new axon grows out from the cell body following the path formed by Schwann cells.

 The sheath contains regularly-spaced gaps (nodes of Ranvier).  The Schwann cell cytoplasm that is not displaced to the periphery during myelin formation forms the Scmidt-Lanterman clefts or incisures that can become numerous with aging.

 The myelin sheath acts as an insulator  Currents are carried by ions through extracellular fluid around myelin sheath  Sheath blocks ionic currents across the membrane

 Current flows across membrane only at nodes  Impulse appears to leap from node to node

Classification of Nerve Fibers

1. Presence of coverings: a. Medullated nerve fiber with neurolemma- motor nerve fibers are the biggest among these varieties; oblique lines in the myelin sheath of the axis cylinder (Schmidt Lantermans lines or incisures of Schmidt) may represent the neuro-keratin framework of myelin or just artifacts caused by neurolemmal folds.  The myelin is covered externally by the Schwann sheath. Both disappear before the nerve fiber ends so that all nerve endings are naked.  A thin fibrous CT sheath outside the neurolemma (sheath of Henle) forms part of the endoniurium that carries blood vessels to individual nerve fibers. b.Medullated nerve fiber without neurolemma- found only in the white matter; composed of the axis cylinder with axolemma and covered by myelin sheath. Nodes of Ranvier are not prominent; lying in rows between the fibers are interfascicular glia cells arranged in the form of a membrane.

c.Non-medullated nerve fiber with neurolemmaconstitutes majority of sympathetic nerves termed REMAK fibers; composed of thin axis cylnder with axolemma and covered by a thin neurolemma; nodes of Ranvier absent. d.Non-medullated nerve fiber without neurolemmacomposed only of the axis cylinder; found in portions of nerve processes arising directly from cell bodies located in the gray matter.

Ultrastructural features of myelinated (A) and unmyelinated (B) nerve fibers. (1) Nucleus and cytoplasm of a Schwann cell; (2) axon; (3) microtubule; (4) neurofilament; (5) myelin sheath; (6) mesaxon; (7) node of Ranvier; (8) interdigitating processes of Schwann cells at the node of Ranvier; (9) side view of an unmyelinated axon; (10) basal lamina.

EM of a peripheral nerve containing both myelinated (M) and unmyelinated (U) nerve fibers. The reticular fibers (RF) seen in cross section belong to the endoneurium. Near the center of the figure is a Schwann cell nucleus (S). The perineurial cells (P [over a nucleus], arrows) form a barrier that controls access of materials to nerve tissue. Inset: Part of an axon, where numerous neurofilaments and microtubules are seen in cross section.

2.Diameter:  Group A- large fibers that conduct at 15-100 m/sec; motor and sensory fibers  All myelinated; touch, pressure, proprioreception, heat, cold, skeletal muscle motor nerves; exist where quick reactions are critical  Group B- conduct 3-14 m/sec; visceral sensory fibers  Group C- unmyelinated fibers conducting at 0.5-2 m/sec; autonomic and some sensory fibers 3.Functional systems:  Afferent (incoming) pathway- spinothalamic, spinocerebellar  Efferent (outgoing) pathway- cortico-bulbar, corticospinal

Nerve Trunk
 Made up of several fasciculi as bundles of nerve fibers covered by a CT covering termed the epiniurium.  This covering sends out septa (periniurium) that surrounds bundles of nerve fibers; the latter send out septa (endoniurium) around individual nerve fibers which is so closely applied to the neurolemma it is difficult to distinguish them from each other.  Blood vessels supplying the endoniurium are termed vasa vasorum, while the nerve fibers within the septa are called nervi vasorum.

SYNAPSE
 Site of transneuronal transmission of an impulse  The number of synapses in a neuron varies: a motor neuron may have 1800; cerebellar granule cells have only a few; a Purkinje cell may have several hundred thousands upon its dendrites.  Their forms may also vary: axo-dendritic (axon dendrite), axo-somatic (axon-perikaryon), axo-axonic (axon-axon)

 Each type of neuron can be distinguished by its synaptic terminations.  They could be tiny swellings along the axon (synapses en passant), or at the tips of axonal branches as knoblike expansions (boutons terminaux)  These terminal twigs form bouquets or loose baskets adhering to the soma or dendrites of another neuron.

 At the synapse, the presynaptic (contain neurotransmitter vesicles and numerous mitochondria) and post-synaptic membranes are separated by the synaptic cleft, where desmosomes help maintain cohesion of synapsing cells.

 There is no cytoplasmic continuity of neurons at the synapse. This forms the basis for the neuron doctrine which holds that each mature neuron represents a cellular unit that is anatomically separate from and tropically independent of other neurons.  The release of a neurotransmitter substance from the presynaptic vesicles, its passage across the synaptic cleft, & its binding to an ion-channel-coupled receptor on the postsynaptic terminal is involved in the transmission of activity from one neuron to another or to an effector.

 After stimulation of the postsynaptic neuron, the neurotransmitter is degraded in the cleft and endocytosed by coated pits.  Removal of excess transmitter prevents continuous firing of the postsynaptic neuron in response to a single presynaptic stimulus.

SYNAPTIC TRANSMISSION

 To date, neuroactive substances include: acetylcholine, monoamines (3 catecholamines: adrenaline, dopamine, noradrenaline; 2 indolamines: serotonin and gamma-amino butyric acid or GABA, asparate, glutamate, glycine, histamine, taurine).  Neuropeptides are used elsewhere in the body (e.g. digestive tract hormones, endorphins, encephalins, releasing hormones).  They are important in regulating feelings and drives, such as pain, pleasure, hunger, thirst and sex (nitric oxide has been shown to mediate the neural aspects of penile erection).  Variety of actions of neuroactive substances: Multiple transmitters which now seem to be the rule for neurons A given transmitter may have different actions in different situations

Effect of a neuroactive substance on its target cell is determined exclusively by the postsynaptic receptors to which it binds.

 Mechanisms for modulating transmitter release and reception: Neuromodulator binds to 2nd-messenger-coupled receptors which activate messenger systems via G-proteins. Once released, these proteins bind to autoreceptors which act to inhibit or facilitate transmitter release. Regulation of number of synaptic vesicles through association of neuromodulator with phosphoproteins and 2nd messenger proteins (e.g. synapsin-I and II, synaptotagmin, synaptophysin) which influence neurotransmitter synthesis, transport and packaging in vesicles, clustering, cytoskeletal anchoring, dissociation, docking fusion, release of contents, membrane reuptake and recycling.

PERIPHERAL NERVE ENDINGS

1.Endings in Epithelium:  Ordinary epithelial cells- naked axis cylinder dissociates into its component neurofibrils that terminate on surface of epithelium as terminal boutons (boutons terminaux, end feet of Held, or neuropodia).  They mediate the general sensation of pain.  Tactile cell of Merkelpolyhedral, vesicular cells found in the middle layer of stratified squamous epithelium; naked neurofibril ends in cup-like expansion called tactile meniscus; they signal prolonged touch or pressure on the skin.

 Neuro-epithelium- found only in special sense organs (taste buds of oral cavity), organ of Corti of internal ear, retina of eyes and olfactory portion of nasal cavity)  Neurofibrils end with chief or sensory cells of neuroepithelium  Free sensory endings are abundant where sensitivity is highly developed (respiratory mucosa, peritrichial nerve endings of hair follicles)

2.Endings in CT: a.Free neurofibrils in ground substance- may end in the usual terminal arborization, other types may form interlacing network or with glomerulus; common in tendons, CT of respiratory passages, intestinal mucosae, meninges of brain and spinal cord, skin and oral cavity; mediate general sensation of pain.

b.Non-capsulated end (receptor) organs- they have very thin areolar CT sheath.  Tactile or Meissners Corpuscle- CT sheath is continuous with fibrous capsule of organ before myelin sheath disappears, and axon winds spirally among cells. Limited to the hairless area of the skin, e.g. cutaneous papillae of fingertips, lips, palms, soles, nipples and conjunctiva.  Though considered a fast-acting mechanoreceptor, its capsule makes it tuned to low-frequency sinusoidal mechanical stimuli.

 Ruffinis end organ or Terminal cylinder- nerve fiber is naked before entering the organ, forms a plexus and ends in terminal boutons; found in subcutaneous tissue of fingertips; they are low-threshold stretch receptors of the skin, and mediate heat sensation.

c.Capsulated End Organs  End bulb of Krause- myelinated fibers lose myelin on entering the capsule and form terminal arborizations; found in conjunctiva, tongue, epiglottis, nasal cavity, peritoneum and other serous membranes, glans penis and clitoris; tendons, ligaments and synovial membranes and in CT of nerve trunks.

 Pacinian (vater-Pacini) corpuscle- largest and most widely distributed of encapsulated receptors.  They are lamellated structures supplied by a large myelinated fiber with a naked cylinder that ends in terminal boutons  Found in subcutaneous tissue of hand and foot, palms and soles, peritoneum, pleura, mesenteries, penis, clitoris, urethra, nipple, mammary glands, pancreas, and visceral walls; numerous in periosteum, ligaments and joint capsules  They mediate deep pressure sensation (vibration receptor); also possible blood pressure regulators

 Golgi Mazzoni corpuscle- single myelinated fiber forms arborization with varicosities and terminal expansions.  They resemble Pacinian bodies except that their lamellated capsule is thinner, granular core of protoplasm is more abundant, and are smaller in size; mediate deep pressure.

2. Endings in Muscle: a. Motor nerve endings (motor end-plate or myoneural junction)- specialized junctional region at the termination of a motor nerve on skeletal muscle fibers  Recognized as a slight elevation on muscle fibers with a local accumulation of nuclei of 2 types: 1. Arborization nuclei- belong to Schwann cells; collectively termed teloglia 2. Fundamental or sole nuclei- larger and pale staining; belong to underlying muscle fibers of motor unit. The termination of the axis cylinder occupies recesses in muscle surface is called synaptic trough or primary synaptic cleft  The ribbon-like lamellae specialization of surface of muscle fiber is called the subneural apparatus  Teloglial cells cover the outer surface of the axon terminal  Vesicles in the subneural apparatus are similar to those of axo-dendritic synapses by having cholinesterase activity.

b.Sensory nerve endings in Striated muscle (neuromuscular spindle)- mediate sensation of position and movement for postural and phasic adjustments of skeletal muscle.  They consist of modified striated muscle (intrafusal) fibers and their nerve endings are enclosed in a common sheath.

Skeletal muscle cannot contract without stimulation from a motor neuron

 The motor nerves are small, myelinated fibers from the gamma neurons of the CNS (large alpha neurons in the ventral gray horn of the spinal cord send their axons to ordinary skeletal muscle); they regulate the sensitivity of the spindle receptors.  The sensory nerve receptors function as stretch receptors, generating impulses when there is stretching of the intrafusal fibers.

c.Nerve Endings in Cardiac and Smooth musclesupplied by ANS  Motor Nerve Endings form a rich plexus in CT between muscle cells and fibers.  Nerve endings are epilemmal, i.e., the termination is on the surface of sarcolemma without penetrating the sarcoplasm.  Sensory nerve endings are located mostly within areolar CT between muscle cells; they are also epilemmal in nature.

d.Nerve Endings in Tendons (neurotendinal spindles)may be simple or encapsulated (give rise to pain sensation), or composite (tendon organ of Golgi).  These are large, fast-conducting nerve fibers which have a higher threshold to stretch than the neuromuscular spindle.  They discharge afferent impulses in response to both stretch and muscle contraction.

Two types exist: 1)Baroreceptors (presso-receptors)- mechanoreceptors in the walls of aorta and carotid sinus, and dilatation of common carotid artery.  They regulate arterial blood pressure. An elevation stretches the nerve endings and elicits a carotid sinus reflex. The afferent nerve impulses inhibit the vasomotor centers of the medulla and excite the vagal center. The blood pressure is then lowered as a result of vasodilatation and decrease cardiac rate via the ANS. 2)Chemoreceptors- convert chemical stimuli to nerve impulses, e.g.: olfactory epithelium of nose, taste buds of tongue; aortic and carotid bodies, glomus pulmonale (pulmonary arteries).  Their structural complexity indicates that they have endocrine functions that could be related to chemoreception.

SPINAL CORD
 The white matter appears externally with the gray matter assuming an H-shape.  The central canal is the remnant of the embryonic neural tube and lined by ependymal cells.  The ventral horns (legs of the H) form the anterior horns containing motor neurons that compose the ventral roots of the spinal nerves. It also forms the posterior horns (arms of the H) which receive sensory fibers from neurons in the spinal ganglia (dorsal roots).

 Gray matter appears dark in color due to absence of myelin.  Gray matter found in certain areas of the white matter are called nuclei or ganglia.  Gray matter is composed of 3 elements:  Nerve cell bodies- arranged in columns in the spinal cord, in layers in the brain, or masses of nerve cells in the brain nuclei  Proximal portions of axons and dendrites  Neuroglia- mostly of the protoplasmic variety, forming a meshwork where areolar tissue and small blood vessels are found.  The white matter contains only myelinated or non-myelinated fibers, neuroglia (fibrous astrocytes), and scanty areolar CT containing blood vessels; its white color is due to whitish appearance of myelin.

 The cerebellar cortex has a superficial layer of gray matter and a core of white matter. Isolated regions of gray matter (nucleus dentatus, emboliformis, globosi, fastigii) appear in the interior of the white matter.  The cerebellar cortex has 3 layers:  Outer molecular layer- few cells and myelinated fibers. Superficial cells are stellate, with short, thin dendrites C and fine myelinated axons that run horizontally. The E larger, deeper cells near the Purkinje cells are known as R basket cells, a narrow plexus of myelinated fibers E composed of collaterals from the axons of Pukinje cells B is found in its deepest portion. E  Middle ganglionic layer- consists of Purkinje cells. L  Granular layer- composed of small, multipolar cells with L short dendrites which arborize in peculiar clawlike U endings. Scattered throughout are Golgi type II cells M (cells of van Gehucten) with processes that enter the molecular layer.

BC, basket cells; BV, blood vessels; D, dendrites; F, fibers; G, Golgi type II cells; Gr, granular layer; Mol, molecular layer; Pia, pia mater; Pkj, Purkinje cells; WM, white matter

CEREBRUM
 The gray matter in the cerebral cortex overlies the white matter (medullary substance) which is composed of bundles of myelinated (association, projection, commissural) fibers passing in all directions.  Cortical Cells and Fibers: Pyramidal cells- upper pointed end of cell is continued toward the brain surface as the apical dendrite; a number of horizontally running basal dendrites spring from the cell body and arborize in the vicinity of the cell. The axon descends towards the medullary substance to enter the white matter as a projection or association fiber.

Stellate or granule cells- dendrites pass in all direction, a short axon ramifies close to the cell body. Cells that have no apical dendrite are known as star pyramids. They are numerous in the internal granular layer. Spindle or fusiform cellsfound in the deepest layer, with their long axis usually vertical to the surface. Horizontal cells of Cajalsmall fusiform cells found in most superficial layer; their long axons run horizontally and arborize within that layer. Cells of Martinotti- small, polygonal cells where axons are directed vertically. They are present in all cell layers; some arborize in the same layer, while others send collaterals to a number of layers.

The cortex has a laminated structure. From the surface to the medullary substance, these layers include: 1.Molecular or plexiform layer- consists of cells with horizontal axons (cells of Cajal), and Golgi type II cells. Within the layer are found dendritic ramifications of pyramidal and fusiform cells, and the axonal endings of the cells of Martinotti. 2.External granular layer- closely packed cells with apical dendrites that terminate in the molecular layer; their axons terminate in the cortical layer. 3.External pyramidal layer- medium-sized pyramidal cells occupy its superficial layer; larger ones are in the deeper layer. Their apical dendrites go to the superficial layer; axons enter the white matter as association or commissural fibers. Also found in the outer layer are horizontal myelinated fibers forming the band of Kaes-Bechterew.

4. Internal granular layer- composed of closely packed, small stellate cells with axons ramifying within the layer. It is permeated with a horizontal plexus of myelinated fibers, forming the external band of Baillarger, considered to be terminal ramifications of the thalaco-cortical fibers. 5. Internal pyramidal or ganglionic layer- consists of medium-sized and the giant pyramidal cells of Betz which constitute the pyramidal tract; they are intermingled with granule cells and the cells of Martinotti. The axons enter the white matter chiefly as projection fibers; the horizontal fiber plexus in the deeper portion constitutes the internal band of Baillarger. 6. Multiform layer or Layer of fusiform cells- contains spindle-shaped cells whose long axis are perpendicular to the cortical surface; also contains granule, Martinotti and stellate cells. The whole layer is pervaded by fiber bundles that enter or leave the medullary substance.

M E N I N G E S

 The CNS is covered by membranes called meninges which are richly supplied with sympathetic nerves. There are 3 types: 1.Dura Mater or pachymeninx- the external meninx made up of dense CT continuous with the periosteum of skull bones. The internal surface is covered by simple squamous epithelium of mesenchymal origin. It is separated from the arachnoid by the subdural space. The cranial dura mater has 2 layers:  Endosteal layer- outer layer of dense CT containing blood vessels and nerves. This layer is the periosteum on the inner surface of cranial bones.  Fibrous layer- inner layer of dense fibrous CT with a single layer of mesothelial cells on its inner surface. It is separated from the outer layer to form the venous sinuses of the brain; it is also deflected inward to extend into large fissures of the brain, e.g. falx cerebri or tentorium cerebelli.

2.Arachnoid- thin netlike membrane devoid of blood vessels. The arachnoid bridges the sulci and fissures of the brain and spinal cord surfaces, forming subarachnoid spaces (cisternae) filled with cerebrospinal fluid. It also perforates the dura mater in some regions, forming protrusions containing centrally located trabeculae (arachnoid villi or Pacchonian corpuscles). Their function is to transfer cerebrospinal fluid into the blood of the venous tissues. 3.Pia Mater- thin, richly vascularized CT closely adherent to surface of brain and spinal cord. Attached to the pia are the inner strands of the arachnoid; their intimate relations give rise to the pia-arachnoid or leptomeninges. Their main elements are fixed fibroblasts and macrophages. Blood vessels penetrate the CNS through tunnels covered by pia mater, termed perivascular spaces. In the CNS, they are covered by expansions of neuroglial processes, and separate the CNS from the cerebrospinal fluid.

4.Choroid Plexus- found in the roof of the 3rd and 4th ventricles, and part of the wall of the 2 lateral ventricles. The main function is to secrete CSF by selective ultrafiltration of blood plasma.  The plexus is composed of loose CT (highly cellular, contains many macrophages) of the pia mater, covered by simple columnar epithelium of neural tube origin.

 Cerebrospinal Fluid (CSF)- elaborated by the choroid plexus; completely fills ventricles, central canal of the spinal cord, subarachnoid space and the perivascular space.  It is important for the metabolism of the CNS, protects the nervous system from concussions and mechanical injuries. The fluid resembles the aqeous humor of the eye.  In the normal adult, ventricular cavities form a continuous channel for the flow of CSF.  The cavity is dilated in the following regions: 2 lateral venticles in the cerebral hemisphere; 3rd ventricle in the thalamus, the 4th ventricle in the medulla oblongata and pons varolli. From these ventricles they flow into the subarachnoid space, and via the arachnoid villi they return into venous circulation.  A decrease in the absorption of CSF results to hydrocephalus which promotes a progressive enlargement of the head followed by mental impairment and muscular weakness).

 The blood-brain or hematoencephalic barrier controls the passage of certain substances from the blood to nerve tissue, protecting neurons from extraneous influences and prevents certain antibiotics and chemotherapeutic agents from reaching the CNS.  Occluding junctions which provide continuity in endothelial cells of capillaries from the pia mater in the choroid plexus represent the main structural component of the barrier.  The capillaries are unlike those found elsewhere in the brain; they have thin walls and fenestrations closed by thin diaphragms, and are held together by tight junctions with neuroglial processes.

HISTOPHYSIOLOGY OF NERVOUS TISSUE

 Axonal Transport- involves both neurofilaments and neurotubules. This movement of metabolic products through the axoplasm toward the terminal arborization can be anterograde (orthograde), dependent on the microtubuleassociated protein kinesin; return of worn materials to the soma for degradation or reutilization is retrograde.  The latter type depends on the protein dynein; a liability since it may carry tetanus toxins and neurotropic viruses (Herpes simplex and rabies) directly to CNS cell bodies

Signal Generation and Transmission 1.Resting membrane potential- The [K+] is 20x higher inside than outside, while the [Na+] is 10x higher outside than inside. In this state of equilibrium, the inside of the cell is negatively charged (-40 to 70 mV) relative to the outside; this potential difference is termed the resting potential, maintained by ion-pumps in the plasma membrane. 2.Action potential  Firing and propagation of action potential- binding of neurotransmitter to receptors in the postsynaptic membrane causes its depolarization (-90 to 70 mV). Voltage-gated Na+ channels are opened when the threshold level is reached, reversing the membrane potential. A wave of depolarization (propagation) spreads along the surface of the neuron as Na+ ions diffuse to adjacent sites within the cell. These events are referred to as the firing of the action potential. It is an all-or-none event and will not occur unless the threshold is reached.

Refractory period- reversal of the membrane potential at threshold causes voltage-gated K+ channels to open, resulting to repolarization. The membrane may achieve an even greater potential difference (hyperpolarization) before stabilizing at normal levels, resulting to inhibitory responses.  The refractory period is the interval between the firing of an action potential and restoration of the resting potential during which an impulse cannot be generated. Na+/K+ ATPase helps restore the balance of these ions during the refractory period.

3.Direction of signal transmission- when the action potential is set off by neurotransmitters crossing the synapse, the sequence of depolarization is usually from dendrites, axon, synapse, next neuron or end organ (orthodromic spread). Two factors prevent this spread toward the cell body (antidromic): (1) the portion of the axon directly behind the newly depolarized region is refractory; and (2) the signal cannot be propagated in a reverse direction across a synapse. 4.Saltatory conduction- depolarizaton occurring at nodes of Ranvier, which is more rapid conduction of the impulse, less dramatic changes in ion concentration, and a lower energy requirement for repolarization.  Blocking signal transmission- cold, heat, pressure and local anesthetics on a nerve fiber can block impulse conduction. Certain poisons block ionic channels and prevent propagation of the action potential.

RESPONSE OF NERVOUS TISSUE TO INJURY

 Damage to Cell Body- no replacement takes place because mature neurons cannot divide. A neuron that makes synaptic contact with only 1 neuron undergoes autolysis when the other is destroyed (transneuronal degeneration).  Damage to the axon:  Primary, ascendant or retrograde degeneration- proximal to the site of injury, the axon and sheath degenerate in 1 or 2 internodes before the injured axon is sealed off in about 2 weeks.  The cell body enlarges, dispersion of the Nissl substance occurs (chromatolysis), nucleus moves to an eccentric position.  Secondary, Wallerian or descendant degeneration- distal to the site of injury, both axon and myelin sheath undergo complete degeneration in 2-3 days. Nearby Schwann cells proliferate, phagocytose the tissue, and invade the remaining endoneurial sheath.

Regeneration: Neuronal plasticity refers to the property of neuronal circuits to be reorganized by the growth of neuronal processes, forming new synapses to replace the ones lost by injury. Thus, new communications are established with some degree of functional recovery. Regeneration begins in the 3rd week after an injury. Nissl bodies reappear, proximal stump of the axon give rise to processes called neurites, one of which grows into the endoneurial sheath. Guided by growth factors (neurotrophins) produced by the neurons, glial cells, Schwann cells or the target cell, it establishes connection with another neuron, or end organ. If the cut ends of a severed nerve are matched according to size and arrangement of fascicles and sutured together by their epineural sheaths within 3-4 weeks after injury, sensory and motor innervation can often be restored. Where there is an extensive gap between proximal and distal segments (or when the distal segment disappears, as in amputation), the newly grown nerve fibers form a swelling (neuroma) that can be a source of spontaneous pain.

RESPONSE OF NERVOUS TISSUE TO INJURY  Damage to the axon: 1.Primary, ascendant or retrograde degenerationproximal to the site of injury, the axon and sheath degenerate in 1 or 2 internodes before the injured axon is sealed off in about 2 weeks.  The cell body enlarges, dispersion of the Nissl substance occurs (chromatolysis)  Nucleus moves to an eccentric position.

2.Secondary, Wallerian or descendant degenerationdistal to the site of injury, both axon and myelin sheath undergo complete degeneration in 2-3 days. Nearby Schwann cells proliferate, phagocytose the tissue, and invade the remaining endoneurial sheath. Regeneration:  Neuronal plasticity refers to the property of neuronal circuits to be reorganized by the growth of neuronal processes, forming new synapses to replace the ones lost by injury. Thus, new communications are established with some degree of functional recovery.  Regeneration begins in the 3rd week after an injury. Nissl bodies reappear, proximal stump of the axon give rise to processes called neurites, one of which grows into the endoneurial sheath.

 Guided by growth factors (neurotrophins) produced by the neurons, glial cells, Schwann cells or the target cell, it establishes connection with another neuron, or end organ.  If the cut ends of a severed nerve are matched according to size and arrangement of fascicles and sutured together by their epineural sheaths within 3-4 weeks after injury, sensory and motor innervation can often be restored.  Where there is an extensive gap between proximal and distal segments (or when the distal segment disappears, as in amputation), the newly grown nerve fibers form a swelling (neuroma) that can be a source of spontaneous pain.  Damage to Cell Body- no replacement takes place because mature neurons cannot divide. A neuron that makes synaptic contact with only 1 neuron undergoes autolysis when the other is destroyed (transneuronal degeneration).

A: Normal nerve fiber, with its perikaryon and effector cell (striated skeletal muscle). B: When the fiber is injured, the neuronal nucleus moves to the cell periphery, and Nissl bodies become greatly reduced in number. The nerve fiber distal to the injury degenerates along with its myelin sheath. Debris is phagocytosed by macrophages. C: The muscle fiber shows a pronounced denervation atrophy. Schwann cells proliferate, forming a compact cord penetrated by the growing axon. D: The nerve fiber regeneration was successful. E: When the axon does not penetrate the cord of Schwann cells, its growth is not organized.