Nervous Tissue Summary 2021 PDF

University of Tripoli Faculty of Medicine Department of Histology and Genetics Dr. Ahmeda I. Benjama Histology HS141 Nervous Tissue Summary of basic histology...

University of Tripoli Faculty of Medicine Department of Histology and Genetics Dr. Ahmeda I. Benjama Histology HS141 Nervous Tissue Summary of basic histology 2021 1 Ahmeda Benjama  Histology of Nervous Tissue Anatomically, the nervous system is divided into the following: 1- The central nervous system (CNS) consists of the brain and the spinal cord, which are located in the cranial cavity and spinal canal, from (efferent or motor nerves) and to (the afferent or sensory nerves of) the CNS. 2- The peripheral nervous system (PNS) consists of cranial, spinal, and peripheral nerves that conduct impulses.  Nerve tissue consists of two principal types of cells: neurons and supporting cells.  The neuron or nerve cell is the functional unit of the nervous system  Supporting cells are nonconducting cells that are located close to the neurons. They are referred to as neuroglial cells or simply glia.  Development of Nerve tissue The nervous system develops from ectoderm, beginning in the third week of development. Cells of the neural tube will give rise to the entire CNS including neurons and most glial cells. Cell derived from the neural crest will form all components of the PNS and also contribute to certain non-neural tissues.  Neurons: The function unit of both the CNS and PNS is the neuron. Most neurons have three main parts:- 1- The Cell body (also called the perikaryon or soma) which contains the nucleus and most of the cell’s organelles and serves as the synthetic or trophic center for the entire neuron. 2- The dendrites, which are the numerous elongated processes extending from the perikaryon and specialized to receive stimuli from other neurons at unique sites called synapses. 3- The axon, which is a single long process ending at synapses specialized to generate and conduct nerve impulses to other cells (nerve, muscle, and gland cells). Axons may also receive information from other neurons, information that mainly modifies the transmission of action potentials to those neurons. Neurons and their processes are extremely variable in size and shape. Cell bodies can be very large, measuring up to 150 μm in diameter. Other neurons, such as the cerebellar granule cells, are among the body’s smallest cells.  Neurons can be classified in many ways:- I- Functionally the nervous system consists of: 1. Sensory division (afferent): receiving stimuli from receptors throughout the body A. Somatic – sensory input perceived consciously (eg, from eyes ears, skin, musculoskeletal structures) B. Visceral – sensory input not perceived consciously (eg, from internal organs and cardiovascular structures) 2. Motor division (efferent) : sending impulses to effector organs A. Somatic – motor output controlled consciously or voluntarily (eg, by skeletal muscle effectors) B. Autonomic – motor output not controlled consciously (eg, by heart or gland effectors) The autonomic motor nerves, comprising what is often called the autonomic nervous system (ANS), all have pathways involving two neurons: a preganglionic neuron with the cell body in the CNS and a postganglionic neuron with the cell body in a ganglion. 2 Ahmeda Benjama The ANS has two divisions: (1) The parasympathetic division, with its ganglia within or near the effector organs, maintains normal body homeostasis. (2) The sympathetic division has its ganglia close to the CNS and controls the body’s responses during emergencies and excitement. ANS components located in the wall of the digestive tract are sometimes referred to as the enteric nervous system. Interneurons establish relationships among other neurons, forming complex functional networks or circuits in the CNS. Interneurons are either multipolar or anaxonic and comprise 99% of all neurons in adults. In the CNS most neuronal perikarya occur in the gray matter, with their axons concentrated in the white matter. In the PNS cell bodies are found in ganglia and in some sensory regions, such as the olfactory mucosa, and axons are bundled in nerves. II- According to the number of processes extending from the cell body (Figure 9–4):- Multipolar neurons, each with one axon and two or more dendrites, are the most common. Bipolar neurons, with one dendrite and one axon, comprise the sensory neurons of the retina, the olfactory epithelium, and the inner ear. Unipolar or pseudounipolar neurons, which include all other sensory neurons, each have a single process that bifurcates close to the perikaryon, with the longer branch extending to a peripheral ending and the other toward the CNS. Anaxonic neurons, with many dendrites but no true axon, do not produce action potentials, but regulate electrical changes of adjacent CNS neurons.  Cell body (Perikaryon or soma):- The neuronal cell body contains the nucleus and surrounding cytoplasm, exclusive of the cell processes. Most cell bodies are in contact with a great number of nerve endings conveying excitatory or inhibitory stimuli 3 Ahmeda Benjama generated in other neurons. Cytoplasm of perikarya often contains numerous free polyribosomes and highly developed RER, indicating active production of both cytoskeletal proteins and proteins for transport and secretion. Histologically these regions with concentrated RER and other polysomes are basophilic and are distinguished as chromatophilic substance (or Nissl substance, Nissl bodies) (Figure 9–3). The Golgi apparatus is located only in the cell body, but mitochondria can be found throughout the cell and are usually abundant in the axon terminals. In both perikarya and processes microtubules, actin filaments, and intermediate filaments are abundant, with the latter formed by unique protein subunits and called neurofilaments in this cell type. Some nerve cell bodies also contain inclusions of pigmented material, such as lipofuscin, consisting of residual bodies left from lysosomal digestion. The large Purkinje neuron of cerebellum has many dendrites (D) emerging from its cell body (CB) and forming branches. The small dendritic branches each have many tiny projecting dendritic spines (DS) spaced closely along their length, each of which is a site of a synapse with another neuron.  Dendrites Dendrites (Gr. dendron, tree) are typically short, small processes emerging and branching off the soma (Figure 9– 3). Usually covered with many synapses, dendrites are the principal signal reception and processing sites on neurons. For example, up to (200,000 axonal endings can make functional contact with the dendrites of a single large Purkinje cell of the cerebellum). Dendrites become much thinner as they branch. In the CNS most synapses on dendrites occur on dendritic spines. 4 Ahmeda Benjama Dendritic spines serve as the initial processing sites for synaptic signals and occur in vast numbers. Dendritic spine morphology depends on actin filaments and changes continuously as synaptic connections on neurons are modified.  Axons Most neurons have only one axon, typically longer than its dendrites. Axonal processes vary in length and diameter according to the type of neuron. Axons of the motor neurons that innervate the foot muscles have lengths of nearly a meter; large cell bodies are required to maintain these axons, which contain most of such neurons’ cytoplasm. The plasma membrane of the axon is often called the axolemma and its contents are known as axoplasm. Axons originate from a pyramid-shaped region of the perikaryon called the axon hillock (Figure 9–3), just beyond which the axolemma has concentrated ion channels which generate the action potential. Axons of interneurons and some motor neurons also have major branches called collaterals that end at smaller branches with synapses influencing the activity of many other neurons. Each small axonal branch ends with a dilation called a terminal bouton (Fr. bouton, button) that contacts another neuron or non-nerve cell at a synapse to initiate an impulse in that cell. Axoplasm contains mitochondria, microtubules, neurofilaments, and transport vesicles, but very few polyribosomes or cisternae of RER, features which emphasize the dependence of axoplasm on the perikaryon. If an axon is severed from its cell body its distal part quickly degenerates and undergoes phagocytosis. In addition to impulse conduction, an important function of the axon is axonal transport between soma and the axon terminals. By Anterograde transport along axonal microtubules via kinesin from the soma to the synaptic terminals. Retrograde transport in the opposite direction along microtubules via dynein carries certain other macromolecules, such as material taken up by endocytosis (including viruses and toxins), from the periphery to the cell body.  Nerve Impulses ( Action potential):- It is an electrochemical process initiated at the axon hillock when other impulses received at the cell body or dendrites meet a certain threshold. The action potential is propagated along the axon as a wave of 5 Ahmeda Benjama  membrane depolarization produced by voltage-gated Na+ and K+ channels in the axolemma that allow diffusion of these ions into and out of the axoplasm. Most synapses act by releasing neurotransmitters, which are usually small molecules that bind specific receptor proteins to either open or close ion channels or initiate second messenger cascades.  Synaptic Communication: Synaptic are the sites where nerve impulse are transmitted from presynaptic cell (neuron) to post synaptic cell (another neuron, muscle cell, or cell of gland). Impulse transmission at synapses can occur electrically or chemically.  Although electrical synapses are uncommon in mammals, they are present in the brain stem, retina, and cerebral cortex, usually represented by gap junctions. Impulses in electrical synapses transmission are much faster than chemical synapse.  Chemical synapses are the most common mode of communication between two nerve cells.  The presynaptic axon terminal (terminal bouton) contains mitochondria and numerous synaptic vesicles from which neurotransmitter is released by exocytosis.  The postsynaptic cell membrane contains receptors for the neurotransmitter, and ion channels or other mechanisms to initiate a new impulse.  Synaptic cleft A 20 nm to 30 nm wide intercellular space separates presynaptic and postsynaptic membranes. At the presynaptic region the nerve impulse briefly opens calcium channels, promoting a Ca2+ influx that triggers neurotransmitter release by exocytosis or similar mechanisms. Immediately the released neurotransmitter molecules diffuse across the synaptic cleft and bind receptors at the postsynaptic region. This produces either an excitatory or an inhibitory effect at the postsynaptic membrane, as follows:  Neurotransmitters from excitatory synapses cause postsynaptic Na+ channels to open, and the resulting Na+ influx initiates a depolarization wave in the postsynaptic neuron or effector cell.  At inhibitory synapses neurotransmitters open Cl- or other anion channels, causing influx of anions and hyperpolarization of the postsynaptic cell, making its membrane potential more negative and more resistant to depolarization. The response in postsynaptic neurons is determined by the summation of activity at hundreds of synapses on that cell. 6 Ahmeda Benjama   Synapses between neurons may be classified as: 1- Axodendritic Synapse. 2- Axosomatic Synapse. 3- Axoaxonic Synapse. 4- Dendrodendritic Synapse. The chemical transmitter used at neuromuscular junctions and some synapses of the CNS is acetylcholine. Within the CNS other major categories of neurotransmitters include: Certain amino acids (often modified), such as glutamateand γ-aminobutyrate (GABA) Monoamines, such as serotonin (5- hydroxytryptamine or 5-HT) and catecholamines, such as dopamine, all of which are synthesized from amino acids. Small polypeptides, such as endorphins and substance P. 7 Ahmeda Benjama   Glial cells Glial support neuronal survival and activities, and are ten times more abundant than neurons in the mammalian brain. Like neurons most glial cells develop from progenitor cells of the embryonic neural plate. In the CNS glial cells surround both the neuronal cell bodies, which are often larger than the glial cells, and the processes of axons and dendrites occupying the spaces between neurons. a. Neuronal cell bodies (N) in the CNS are large than much more numerous glial cells (G). b. With the use of gold staining of neutrofibrils, neuropil (NP) is more apparent.. There are four major kinds of glial cells in the CNS: oligodendrocytes, astrocytes, ependymal cells, and microglial cells. 8 Ahmeda Benjama The interrelationships and major functions of these cells are shown diagrammatically here. I. Oligodendrocytes resemble to Astrocytes but are smaller and contain fewer processes with sparse branching. The darkest stain neuroglial cells, oligodendrocytes are located in both the gray and the white matter of CNS. Their dense cytoplasm contains a relatively small nucleus, abundant RER, many free ribosomes and mitochondria, and a conspicuous Golgi complex. Microtubules also present.  Interfascicular oligodenrocytes:- located in rows beside bundles of axon, are responsible for manufacturing and maintaining myelin about the axon of the CNS, serving to insulate them. Same as in Shawn cell in PNC, except that a single oligodendrocyte may wrap several axons. Where is a single schwan cell wrap one axon in CNS.  Satellite oligodedrocytes are closely applied to cell bodies neurons, their function is not clear. II. Microglia  Less numerous than oligodendrocytes or astrocytes but nearly as common as neurons in some CNS regions.  Microglia are small cells with actively mobile processes evenly distributed throughout gray and white matter.  Microglia do not originate from neural progenitor cells like other glial, but from circulating blood monocytes, belonging to the same family as macrophages and other antigen-presenting cells. 9 Ahmeda Benjama III. Ependymal cells  Are epithelial-like cells that form a single layer lining the fluid-filled ventricles and central canal of the CNS.  (a) Lining the ventricles of the cerebrum, columnar ependymal cells (E) extend cilia and microvilli from the apical surfaces into the ventricle (V).  Ependymal cells have junctional complexes at their apical ends like those of epithelial cells but lack a basal lamina. Other areas of ependyma are responsible for production of Cerebrospinal fluid ( CSF).  (b). Ependymal cells (E) lining the central canal (C) of the spinal cord help move CSF in that CNS region. IV. Schwann Cells Two glial cells occur in the PNS: Schwann cells (sometimes called neurolemmocytes), which surround peripheral nerve fibers, and satellite cells, which surround the nerve cell bodies and are thus found only in ganglia. Major functions of these cells are indicated. ( see last pages).  Schwann cells sometimes called neurolemmocytes.  Found only in the PNS and differentiate from neural crest.  Schwann cells are the counterparts to oligodendrocytes of the CNS.  Having trophic interactions with axons and most importantly forming their myelin sheathes.  However unlike an oligodendrocyte, a Schwann cell forms myelin around a portion of only one axon. 10 Ahmeda Benjama  V. Satellite Cells of Ganglia  Derived from the embryonic neural crest, small satellite cells form a thin, intimate glial layer around each large neuronal cell body in the ganglia of the PNS.  Satellite cells exert a trophic or supportive effect on these neurons, insulating, nourishing, and regulating their microenvironments. Satellite cells are very closely associated with neuronal cell bodies in sensory and autonomic ganglia of the PNS and support these cells in various ways. (a) Nuclei of the many satellite cells (S) surrounding the perikarya of neurons (N) in an autonomic ganglion can be seen by light microscopy, but their cytoplasmic extensions are too thin to see with H&E staining. b) Immunofluorescent staining of satellite cells (S) VI. Astrocytes reveals the cytoplasmic sheets extending from these  Astrocytes are the most abundant glial cells cells and surrounding the neuronal cell bodies (N). of the CNS and are characterized by numerous The layer of satellite cells around each soma is cytoplasmic processes continuous with the myelin sheath around the axon.  Astrocytes are closely associated with Like the effect of Schwann cells on axons, satellite neurons to support and modulate their activities. glial cells insulate, nourish, and regulate the  Astrocytes are the largest of the microenvironment of the neuronal cell bodies. neuroglial cells. They form a net work of cells. 11 Ahmeda Benjama   Astrocytes  Astrocytes within the CNS and communicate with neurons to support and modulate many of their activities.  Some Astrocytes span the entire thickness of the brain, providing a scaffold for migrating neurons during brain development.  Other astrocytes stretch their processes from blood vessels to neurons.  The ends of the processes expand, forming end feet that cover large areas of the outer surface of the vessel or axolemma.  Astrocytes form part of the blood brain barrier (BBB) and help regulate entry of molecules and ions from blood into CNS tissue  Astrocytes do not form myelin. Two kinds of astrocytes are identified:- A. Protoplasmic astrocytes more common of gray matter the brain. These Astrocytes have numerous, short, branching cytoplasmic processes. B. Fibrous Astrocytes: are more common of white matter the brain. These astrocytes have fewer processes, and they are relatively straight. Both types of astrocytes contain prominent bundles of intermediate filaments composed of glial fibrillary acidic protein (GFAP). The filaments are much more numerous in Fibrous Astrocytes.   Central nerve system (CNS):-  The major structures comprising the CNS are the cerebrum, cerebellum, and spinal cord (Figure 9–1).  The CNS is completely covered by connective tissue layers, the meninges, but CNS tissue contains very little collagen or similar material, making it relatively soft and easily damaged by injuries affecting the protective skull or vertebral bones.  Many regions show organized areas of white matter and gray matter, differences caused by the differential distribution of lipid-rich myelin.  The main components of white matter are myelinated axons (Figure 9–14), often grouped together as tracts, and the myelin-producing oligodendrocytes.  Astrocytes and microglia are also present, but very few neuronal cell bodies. Gray matter contains abundant neuronal cell bodies, dendrites, astrocytes, and microglial cells, and is where most synapses occur.  Gray matter makes up the thick cortex or surface layer of both the cerebrum and the cerebellum; most white matter is found in deeper regions. 12 Ahmeda Benjama   Deep within the brain are localized, variously shaped darker areas called the cerebral nuclei, each containing large numbers of aggregated neuronal cell bodies.  In the folded cerebral cortex neuroscientists recognize six layers of neurons with different sizes and shapes. The most conspicuous of these cells are the efferent pyramidal neurons (Figure 9–15). Neurons of the cerebral cortex function in the integration of sensory information and the initiation of voluntary motor responses.  The sharply folded cerebel muscular activity throughout the body and is organized with three layers (Figure 9–16): A cross section of H&E-stained spinal cord shows the transition between white matter (left region) and gray matter (right). The gray matter has many glial cells (G), neuronal cell bodies (N), and neuropil; white matter also contains glia (G) but consists mainly of axons (A) whose myelin sheaths were lost during preparation, leaving the round empty spaces shown. (a) Important neurons of the cerebrum are the (b) From the apical ends of pyramidal pyramidal neurons (P), which are arranged neurons (P), long dendrites extend in the vertically and interspersed with numerous direction of the cortical surface smaller glial cells, mostly astrocytes, in the eosinophilic neuropil. 13 Ahmeda Benjama  (a) The cerebellar cortex is convoluted with many distinctive small folds. cerebellar medulla (M). molecular layers (ML) and granular layers (GL). (b) Higher magnification shows that the granular layer (GL) immediately surrounding the medulla (M) is densely packed with several different types of very small rounded neuronal cell bodies. The outer molecular layer (ML) consists of neuropil with fewer, much more scattered small neurons. At the interface of these two regions a layer of large Purkinje neuron (P) perikarya can be seen. (c) A single intervening layer contains the very large cell bodies of unique Purkinje neurons (P), whose axons pass through the granular layer (GL) to join tracts in the medulla and whose multiple branching dendrites ramify throughout the molecular layer (ML). (d) With appropriate silver staining dendrites from each large Purkinje cell (P) are shown to have hundreds of small branches. A thick outer molecular layer has much neuropil and scattered neuronal cell bodies. A thin middle layer consists only of very large neurons called Purkinje ;These are conspicuous even in H&E-stained sections, and their dendrites extend throughout the molecular layer as a branching basket of nerve fibers (Figures 9–16c and d). A thick inner granular layer contains various very small, densely packed neurons (including granule cells, with diameters of only 4-5 μm) and little neuropil. 14 Ahmeda Benjama   Spinal cord  In cross sections of the spinal cord the white matter is peripheral and the gray matter forms a deeper, H-shaped mass (Figure 9–17).  The two anterior projections of this gray matter, the anterior horns, contain cell bodies of very large motor neurons whose axons make up the ventral roots of spinal nerves  The two posterior horns contain interneurons which receive sensory fibers from neurons in the spinal (dorsal root) ganglia. Near the middle of the cord the gray matter surrounds a small central canal, which develops from the lumen of the neural tube, is continuous with the ventricles of the brain, is lined by ependymal cells, and contains CSF. The spinal cord in cross section always shows bilateral symmetry around the small, CSF-filled central canal (C). Unlike the cerebrum and cerebellum, in the spinal cord the gray matter is internal, forming a roughly H-shaped structure that consists of two posterior (P) horns (sensory) and two anterior (A) (motor) horns, all joined by the gray commissure around the central canal. (a) The gray matter contains abundant astrocytes and large neuronal cell bodies.. (b) The white matter surrounds the gray matter and contains primarily oligodendrocytes and tracts of myelinated axons running along the length of the cord. (c) With H&E staining the large motor neurons (N) of the ventral horns. (d) In the white commissure ventral to the central canal, tracts (T) run lengthwise along the cord. 15 Ahmeda Benjama (a) A diagram of the spinal cord indicates the relationship of the three meningeal layers of connective tissue: the innermost pia mater, the arachnoid, and the dura mater. Also depicted are the blood vessels coursing through the subarachnoid space and the nerve rootlets that fuse to form the posterior and anterior roots of the spinal nerves. The posterior root ganglia contain the cell bodies of sensory nerve fibers and are located in intervertebral foramina. (b) Section of an area near the anterior median fissure showing the tough dura mater (D). Surrounding the dura, the epidural space (not shown) contains cushioning adipose tissue and vascular plexuses. The subdural space (SD) is an artifact created by separation of the dura from underlying tissue. The middle meningeal layer is the thicker weblike arachnoid mater (A) containing the large subarachnoid space (SA) and connective tissue trabeculae (T). The subarachnoid space is filled with CSF and the arachnoid acts as a shock-absorbing pad between the CNS and bone. Fairly large blood vessels (BV) course through the arachnoid. The inner most pia mater (P) is thin and is not clearly separate from the arachnoid; together, they are sometimes referred to as the pia- arachnoid or the leptomeninges. The space between the pia and the white matter (WM) of the spinal cord here is an artifact created during dissection; normally the pia is very closely applied to a layer of astrocytic processes at the surface of the CNS tissue. (X100; H&E). 16 Ahmeda Benjama The dura, arachnoid, and pia maters also surround the brain and as shown here the relationships among the cranial meninges are similar to those of the spinal cord. The diagram includes arachnoid villi, which are out pocketings of arachnoid away from the brain, which penetrate the dura mater and enter blood-filled venous sinuses located within that layer. The arachnoid villi function in releasing excess CSF into the blood. Blood vessels from the arachnoid branch into smaller arteries and veins that enter brain tissue carrying oxygen and nutrients. These small vessels are initially covered with pia mater, but as capillaries they are covered only by the perivascular feet of astrocytes. 17 Ahmeda Benjama A Schwann cell (neurolemmocyte) engulfs one portion along the length of a large-diameter axon. The Schwann cell membrane fuses around the axon and one thin extension of the Schwann cell elongates greatly and wraps itself repeatedly around the axon to form multiple, compacted layers. The Schwann cell membrane wrappings constitute the myelin sheath, with the Schwann cell body always on its outer surface. The myelin layers are very rich in lipid, and provide insulation and facilitate formation of action potentials along the axolemma. Cross section of PNS fibers in the TEM reveals differences between myelinated and unmyelinated axons. Large axons (A) are wrapped in a thick myelin sheath (M) of multiple layers of Schwann cell membrane. The inset shows a portion of myelin at higher magnification in which the major dense lines of individual membrane layers can be distinguished, as well as the neurofilaments (NF) and microtubules (MT) in the axoplasm (A). At the center of the photo is a Schwann cell showing its active nucleus (SN) and Golgi-rich cytoplasm (SC). At the right is an axon around which myelin is still forming (FM). Unmyelinated axons (UM) are much smaller in diameter, and many such fibers may be engulfed by a single Schwann cell (SC). The glial cell does not form myelin wrappings around such small axons but simply encloses them. Whether it forms myelin or not, each Schwann cell is surrounded, as shown, by an external lamina containing type IV collagen and laminin like the basal laminae of epithelial cells. 18 Ahmeda Benjama  The middle diagram shows schematically a myelinated peripheral nerve fiber as seen under the light microscope. The axon is enveloped by the myelin sheath, which, in addition to membrane, contains some Schwann cell cytoplasm in spaces called Schmidt-Lanterman or myelin clefts between the major dense lines of membranes. The upper diagram shows one set of such clefts ultrastructurally. The clefts contain Schwann cell cytoplasm that was not displaced to the cell body during myelin formation. This cytoplasm moves slowly along the myelin sheath, opening temporary spaces (the clefts) that allow renewal of some membrane components as needed for maintenance of the sheath. The lower diagram depicts the ultrastructure of a single node of Ranvier or nodal gap. Interdigitating processes extending from the outer layers of the Schwann cells (SC) partly cover and contact the axolemma at the nodal gap. This contact acts as a partial barrier to the movement of materials in and out of the periaxonal space between the axolemma and the Schwann sheath. The basal or external lamina around Schwann cells is continuous over the nodal gap. The axolemma at nodal gaps has abundant voltage-gated Na+ channels important for impulse conductance in these axons. A longitudinally oriented nerve shows one node of Ranvier (N) with the axon visible. Collagen of the sparse endoneurium (En), blue in this trichrome stain, surrounds the Schwann cells and a capillary (C). At least one Schwanncell nucleus (S) is also clearly seen. (X400). 19 Ahmeda Benjama   Unmyelinated nerve:- During development, portions of several small-diameter axons are engulfed by one Schwann cell. Subsequently the axons are separated and each typically becomes enclosed within its own fold of Schwann cell surface. No myelin is formed by wrapping. Small-diameter axons utilize action potentials whose formation and maintenance do not depend on the insulation provided by the myelin sheath required by large-diameter axons.  Ganglia Ganglia are typically ovoid structures containing neuronal cell bodies and their surrounding glial satellite cells supported by delicate connective tissue and surrounded by a denser capsule. Because they serve as relay stations to transmit nerve impulses, at least one nerve enters and another exits from each ganglion. The direction of the nerve impulse determines whether the ganglion will be a sensory or an autonomic ganglion. Sensory Ganglia Sensory ganglia receive afferent impulses that go to the CNS. Sensory ganglia are associated with both cranial nerves (cranial ganglia) and the dorsal roots of the spinal nerves (spinal ganglia). The large neuronal cell bodies of ganglia (Figure 9–29) are associated with thin, sheet-like extensions of small glial satellite cells (Figures 9–9b and 9–13). Sensory ganglia are supported by a distinct connective tissue capsule and an internal framework continuous with the connective tissue layers of the nerves. The neurons of these ganglia are pseudounipolar and relay information from the ganglion’s nerve endings to the gray matter of the spinal cord via synapses with local neurons. 20 Ahmeda Benjama   Peripheral nerve connective tissue:- (a). The diagram shows the relationship among these three connective tissue layers in large peripheral nerves. The epineurium (E) consists of a dense superficial region and a looser deep region that contains the larger blood vessels. (b) The micrograph shows a small vein (V) and artery (A) in the deep epineurium (E). Nerve fibers (N) are bundled in fascicles. Each fascicle is surrounded by the perineurium (P), consisting of a few layers of unusual squamous fibroblastic cells that are all joined at the peripheries by tight junctions. The resulting blood-nerve barrier helps regulate the microenvironment inside the fascicle. Axons and Schwann cells are in turn surrounded by a thin layer of endoneurium. (X140; H&E). (c) As shown here and in the diagram, septa (S) of connective tissue often extend from the perineurium into larger fascicles. The endoneurium (En) and lamellar nature of the perineurium (P) are also shown at this magnification, along with some adjacent epineurium (E). (X200; PT). (d) SEM of transverse sections of a large peripheral nerve showing several fascicles, each surrounded by perineurium and packed with endoneurium around the individual myelin sheaths. Each fascicle contains at least one capillary. Endothelial cells of these capillaries are tightly joined as part of the blood-nerve barrier and regulate the kinds of plasma substances released to the endoneurium. Larger blood vessels course through the deep epineurium that fills the space around the perineurium and fascicles. (X45). 21 Ahmeda Benjama  (a) A sensory ganglion (G) has a distinct connective tissue capsule (C) and internal framework continuous with the epineurium and other components of peripheral nerves, except that no perineurium is present and that there is no blood-nerve barrier function. Fascicles of nerve fibers (F) enter and leave these ganglia. (X56; Kluver-Barrera stain) (b) (b) Higher magnification shows the small, rounded nuclei of glia cells called satellite cells (S) that produce thin, sheet-like cytoplasmic extensions that completely envelop each large neuronal perikaryon. (X400; H&E). (c) Sympathetic ganglia are smaller than most sensory ganglia but similar in having large neuronal cell bodies (N), some containing lipofuscin (L). Sheets from satellite cells (S) enclose each neuronal cell body with morphology slightly different from that of sensory ganglia. Autonomic ganglia generally have less well developed connective tissue capsules (C) than sensory ganglia. (X400; H&E)  Autonomic Ganglia Autonomic nerves effect the activity of smooth muscle, the secretion of some glands, heart rate, and many other involuntary activities by which the body maintains a constant internal environment (homeostasis). Autonomic ganglia are small bulbous dilations in autonomic nerves, usually with multipolar neurons. Some are located within certain organs, especially in the walls of the digestive tract, where they constitute the intramural ganglia. The capsules of these ganglia may be poorly defined among the local connective tissue. A layer of satellite cells also envelops the neurons of autonomic ganglia (Figure 9–29), although these may also be inconspicuous in intramural ganglia. 22 Ahmeda Benjama Autonomic nerves use two-neuron circuits. The first neuron of the chain, with the preganglionic fiber, is located in the CNS. Its axon forms a synapse with postganglionic fibers of the second multipolar neuron in the chain located in a peripheral ganglion system. The chemical mediator present in the synaptic vesicles of all preganglionic axons is acetylcholine. As indicated earlier autonomic nerves make up the autonomic nervous system. This has two parts: the sympathetic and the parasympathetic divisions. Neuronal cell bodies of preganglionic sympathetic nerves are located in the thoracic and lumbar segments of the spinal cord and those of the parasympathetic division are in the medulla and midbrain and in the sacral portion of the spinal cord. Sympathetic second neurons are located in small ganglia along the vertebral column, while second neurons of the parasympathetic series are found in very small ganglia always located near or within the effector organs, for example in the walls of the stomach and intestines. Parasympathetic ganglia may lack distinct capsules altogether, perikarya and associated satellite cells simply forming a loosely organized plexus within the surrounding connective tissue.  NEURAL PLASTICITY & REGENERATION Despite its general stability, the nervous system exhibits neuronal differentiation and formation of new synapses even in adults. Embryonic development of the nervous system produces an excess of differentiating neurons, and the cells that do not establish correct synapses with other neurons are eliminated by apoptosis. In adult mammals after an injury, the neuronal circuits may be reorganized by the growth of neuronal processes, forming new synapses to replace ones lost by injury. This neural plasticity and reformation of processes are controlled by several growth factors produced by both neurons and glial cells in a family of proteins called neurotrophins. Neuronal stem cells are present in the adult CNS, located in part among the cells of the ependyma, which can supply new neurons, astrocytes, and oligodendrocytes. If the cell bodies are intact, damaged, or severed PNS axons can regenerate by, isolated distal portions of axons from their source of new proteins and organelles, degenerate; the surrounding Schwann cells dedifferentiate, shed the myelin sheaths, and proliferate within the surrounding layers of connective tissue. Cellular debris including shed myelin is removed by blood-derived macrophages, which also secrete neurotrophins to promote anabolic events of axon regeneration. The onset of regeneration is signaled by changes in the perikaryon that characterize the process of chromatolysis: the cell body swells slightly, Nissl substance is initially diminished, and the nucleus migrates to a peripheral position within the perikaryon. The proximal segment of the axon close to the wound degenerates for a short distance, but begins to grow again distally as new Nissl substance appears and debris is removed. The new Schwann cells align to serve as guides for the regrowing axons and produce polypeptide factors that promote axonal outgrowth. Motor axons reestablish synaptic connections with muscles and function is restored. 23 Ahmeda Benjama In an injured or cut peripheral nerve, proximal axon segments can regenerate from their cut ends after a delay. (a). Normal nerve fiber, with its perikaryon, extensive RER (Nissl substance), and effector cell (muscle). (b). When the axon is injured, the RER is greatly reduced initially and the nerve fiber distal to the injury degenerates along with its myelin sheath. (c). In the following weeks after injury, muscle fiber shows denervation atrophy, but Schwann cells proliferate to form a compact cord penetrated by the regrowing axon. The axon grows at the rate of 0.5-3 mm/d. (d). After some months, the nerve fiber regeneration is successful and functional connections with the muscle fiber are restored.  Multiple Sclerosis:- In multiple sclerosis (MS) the myelin sheaths surrounding axons are damaged by an autoimmune mechanism that interferes with the activity of the affected neurons and produces various neurologic problems. T lymphocytes and microglia, which phagocytose and degrade myelin debris, play major roles in progression of this disease. In MS, destructive actions of these cells exceed the capacity of oligodendrocytes to produce myelin and repair the myelin sheaths. 24 Ahmeda Benjama