Nervous_system_I (2).pdf

https://www.nobelprize.org/prizes/medicine/2023/press-release/ 1 https://www.nobelprize.org/prizes/medicine/2021/summary/ 2 Nervous system cells F. Figen Kaymaz MD, PhD Professor of Histology & Embryology [email protected] 3 Learning outcome 1. 2. 3. 4. 5. 6. 7. 8. 9. Be able to i...

https://www.nobelprize.org/prizes/medicine/2023/press-release/ 1 https://www.nobelprize.org/prizes/medicine/2021/summary/ 2 Nervous system cells F. Figen Kaymaz MD, PhD Professor of Histology & Embryology [email protected] 3 Learning outcome 1. 2. 3. 4. 5. 6. 7. 8. 9. Be able to identify neurons with their morphological characteristics be able to define axon, dendrite and pericarion be able to classify neurons by their structural aspects be able to identify glia with their morphological characteristics be able to classify glia according to their location be able to describe the basic components of a synapse be able to classify synapse types completely be able to explain synaptic communication by relating it to neuron structure be able to explain myelinization 4 CELLS OF THE NERVOUS SYSTEM • Neurons (Nerve cell) • Glial cells (Support) 5 Nervous system • Most complex system of the organism • Number of neurons more than 100 million • Number of glial cells > neurons • Each neuron has ~100.000 connection • Ground substance and fibers are not present • It is an integrated network around the organs of the organism • Certain neurons have receptors specialized for receiving different types of stimuli 6 GENERAL PROPERTIES 7 NEURON • Variable in shape: pyramidal, granular, stellate poligonal, round, etc • Number: 10-100 billions of neurons • Mitosis: (–) • Variable in size: 5-150 µm : • 4-5 µm (Granular cells of cerebellum ) • 150 µm (Purkinje cells of cerebellum) 8 Neuron • The functional unit in both the CNS and PNS is the neuron or nerve cell. • Most neurons consist of three main parts: • The cell body, or perikaryon • The dendrites • The axon 9 • The cell body, or perikaryon, which contains the nucleus and most of the cell’s organelles and serves as the synthetic or trophic center for the entire neuron. • The dendrites, which are the numerous elongated pro- cesses extending from the perikaryon and specialized to receive stimuli from other neurons at unique sites called synapses. • 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 transmis- sion of action potentials to those neurons. 10 11 Neurons can be classified according to the number of processes extending from the cell body • Multipolar neurons • Bipolar neurons • Pseudounipolar neurons • Unipolar and apolar neurons • Anaxonic neurons 12 Multipolar neurons • which have one axon and two or more dendrites ¨ Majority • Pyramidal neurons in the cerebral cortex • Purkinje cells in the cerebellar cortex 13 Bipolar neurons • with one dendrite and one axon • Bipolar neurons are found in the retina, olfactory mucosa, and the (inner ear) cochlear and vestibular ganglia, where they serve the senses of sight, smell, and balance, respectively. 14 Unipolar or pseudounipolar neurons • which 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. • Pseudounipolar neurons are found in the spinal ganglia (the sensory ganglia found with the spinal nerves) and in most cranial ganglia. 15 Anaxonic neurons • with many dendrites but no true axon, • do not produce action potentials, but regulate electrical changes of adjacent neurons. 16 17 Nervous components can be subdivided functionally • Sensory neurons are afferent and receive stimuli from the receptors throughout the body. • Motor neurons are efferent, sending impulses to effector organs such as muscle fibers and glands. • Somatic motor nerves are under voluntary control and typically innervate most skeletal muscle; • Autonomic motor nerves control the “involuntary” activities of glands, cardiac muscle, and most smooth muscle. 18 • Interneurons establish relationships among other neurons, forming complex functional networks or circuits (as in the CNS and retina). • Interneurons are generally multipolar or anaxonic and are estimated to include 99% of the neurons in the human CNS. 19 STRUCTURE OF NEURON 1. Neuronal cell body (perikaryon, soma) 2. Dendrites 3. Axons 20 Cell Body (Perikaryon) • The cell body is the neuronal region that contains the nucleus and surrounding cytoplasm. It acts as a trophic center, producing cytoplasm for movement into the processes, although most cell bodies also receive a great number of nerve endings conveying excitatory or inhibitory stimuli generated in other nerve cells. Most nerve cells have a generally spherical, unusually large, euchromatic (pale-staining) nucleus with a prominent nucleolus. The chromatin is finely dispersed, reflecting the intense synthetic activity of these cells. 21 • Cytoplasm of perikarya often contains a highly developed RER with many parallel cisternae and neighboring regions with numerous polyribosomes, indicating active production of both cytoskeletal proteins and proteins for transport and secretion. • Histologically these regions with concentrated RER and other polysomes appear as clumps of basophilic material called chromatophilic substance (or Nissl substance, Nissl bodies) Abundant in large nerve cells such as motor neurons. 22 • 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. 23 Neurofilaments 8-10 nm • Intermediate filaments are abundant both in perikarya and processes and in this cell are often called neurofilaments. • Neurons also contain microtubules identical to those found in other cells. Microtubules 20-30 24 nm • Nerve cells occasionally contain inclusions of pigmented material, such as lipofuscin, consisting of residual bodies left from lysosomal digestion. 25 Dendrites • Dendrites are usually short and divided like tree branches. They are usually covered with many synapses and are the principal signal reception and processing sites on neurons. Most nerve cells have many dendrites, which increase the receptive area of the cell considerably. • The arborization of dendrites makes it possible for one neuron to receive and integrate a great number of axon terminals from other nerve cells. 26 • Unlike axons, which maintain a nearly constant diameter, dendrites become much thinner as they subdivide. • The cytoplasm of the dendrite base is similar to that of the perikaryon, with cytoskeletal elements predominating in the branched regions. • Most synapses impinging on neurons occur on dendritic spines, which are short blunt structures projecting at points along dendrites, visible with silver staining methods. Serve as the initial processing sites for synaptic signals. Dendritic spines are of key importance in the constant changes of the neural plasticity underlying adaptation, learning, and memory. 27 Axons • Most neurons have only one axon, a fine cylindrical process that varies in length and diameter according to the type of neuron. • Axons are usually very long processes. For example, axons of the motor neurons of the spinal cord that innervate the foot muscles may have a length of nearly 100 cm and require large cell bodies for their maintenance. Axons originate from a pyramid-shaped region of the perikaryon called the axon hillock. • The plasma membrane of the axon is often called the axolemma and its contents are known as axoplasm. 28 • Distal end of the axon makes branches called terminal arborization – TELODENDRON • The end point of each branch is a specialized region for synapsis called terminal button. 29 • Axoplasm contains mitochondria, microtubules, neurofilaments, and some cisternae of smooth ER, but essentially no polyribosomes or RER, emphasizing its dependence on the perikaryon for maintenance. If an axon is severed, its peripheral part quickly degenerates. 30 • There is a lively bidirectional transport of small and large molecules along the axon. Organelles and macromolecules synthesized in the cell body move by anterograde transport along the axon from the perikaryon to the synaptic terminals. • Retrograde transport in the opposite direction carries certain other macromolecules, such as material taken up by endocytosis (including viruses and toxins), from the periphery to the cell body. 31 32 • Axonal transport in both directions uses motor proteins on microtubules, Kinesin, a microtubul activated ATPase, mediates anterograde vesicular transport, and the similar ATPase called cytoplasmic dynein provides retrograde transport. • Anterograde and retrograde transports both occur fairly rapidly, at rates of 50-400 mm/d. A much slower anterograde stream (only a few millimeters per day) involves movement of the axonal cytoskeleton itself. This slow axonal transport system corresponds roughly to the rate of axon growth. 33 Synaptic Communication • Synapses are sites where nerve impulses are transmitted from one neuron to another or from neurons and other effector cells. • The structure of a synapse ensures that transmission is unidirectional. • Synapses convert an electrical signal (nerve impulse) from the presynaptic cell into a chemical signal that affects the postsynaptic cell. 34 • 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. A synapse has the following components: 1-Presynaptic axon terminal (terminal bouton) from which neurotransmitter is released by exocytosis from synaptic vesicles. 2- Postsynaptic cell membrane with receptors for the transmitter and ion channels or other mechanisms to initiate a new impulse. 3- A 20- to 30-nm-wide intercellular space called the synaptic cleft separating the presynaptic and postsynaptic membranes. 35 • Neurotransmitters from excitatory synapses cause postsynaptic Na+ channels to open, and the resulting influx of this ion initiates a depolarization wave in that 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. 36 Morphologically, various types of synapses are seen between neurons • If an axon forms a synapse with a cell body, it is called an axosomatic synapse; with a dendrite, axodendritic; or with another axon, axoaxonic. Axoaxonic synapses modulate activity of the other two types. 37 38 GLIAL CELLS & NEURONAL ACTIVITY • Glial cells support neuronal survival and activities, and are ten times more abundant in the mammalian brain than the neurons. In the CNS glial cells surroud both the neuronal cell bodies, which are often larger than glial cells, and the processes of axons and dendrites occupying the spaces between neurons. 39 • the network of cellular processes emerging from neurons and glial cells are collectively called the neuropil 40 NEUROGLIAL CELLS In the CNS In the PNS • Astrocytes • Schwann cells • Satellite cells • Protoplasmic (Gray matter) • Fibrous (White matter) • Oligodendrocyte (Gray & white matter) • Microglia (Gray & white matter) • Ependymal cells (Ventricules) 41 There are six kinds of glial cells; 1- Oligodendrocytes •Oligodendrocytes produce the myelin sheaths around axons that provide the electrical insulation for neurons in the CNS. These are the predominant glial cells in CNS white matter, which is white because of the lipid concentrated in the wrapped membrane sheaths. 42 2- Astrocytes • Astrocytes have a large number of radiating processes and are also unique to the CNS. • Those with relatively few, long processes are called fibrous astrocytes and are typical in white matter; those with many shorter, branched processes are called protoplasmic astrocytes and predominate in the gray matter. • astrocytes communicate directly with one another via gap junctions, forming a very large cellular network for the coordinated regulation of their various activities in different brain regions. 43 1. Protoplasmic astrocytes (gray matter) 2. Fibrous astrocytes (white matter) 44 45 3- Ependymal Cells • Ependymal cells are columnar or cuboidal cells that line the ventricles of the brain and central canal of the spinal cord. In some CNS locations, the apical ends of ependymal cells have cilia, which facilitate the movement of cerebrospinal fluid (CSF), and long microvilli, which are likely involved in absorption 46 EPENDYMAL CELLS 47 4-Microglia • microglia are small cells with short irregular processes evenly distributed throughout gray and white matter. • Unlike other glial cells, microglia migrate through the neuropil, scanning the tissue for damaged cells and invading microorganisms. • They secrete a number of immunoregulatory cytokines and constitute the major mechanism of immune defense in the CNS. • Microglia do not originate from neural progenitor cells like other glia, but from circulating blood monocytes, belonging to the same family as macrophages and other antigenpresenting cells. 48 5-Schwann Cells • Schwann are found only in the Pheripherial Nervous System and differentiate from precursors in the neural crest. • One Schwann cell forms myelin around a segment of one axon, in contrast to the ability of oligodendrocytes to branch and ensheath parts of more than one axon. 49 NERVES ACCORDING TO PRESENCE OF MYELIN SHEATH 50 6- Satellite Cells of Ganglia • Also derived from the embryonic neural crest, small satellite cells form an intimate covering layer over the large neuronal cell bodies in the ganglia of the PNS. • Satellite cells exert a trophic or supportive effect on these neu- rons, insulating, nourishing, and regulating their microenvironments. 51 NEUROGLIAL CELLS 52 53 NEUROGLIAL CELLS 54 ANATOMICAL ORGANIZATION Central Nervous System (CNS) • Brain Peripheral Nervous System (PNS) • Cerebral hemispheres Cerebellum • Spinal cord (Medulla Spinalis) • • Peripheral nerves Cranial nerves (those emerge from brain) Spinal nerves (those emerge from spinal cord) Ganglia Autonomic (sympathetic and parasympathetic) ganglia Sensory (spinal or dorsal root) ganglia Receptors Interoceptive system Exteroceptive system Proprioceptive system 55 FUNCTIONAL ORGANIZATION Sensory Component • Receives and transmits Motor Component • Originates in the CNS impulses to the CNS and transmits impulses for processing to the effector organs a. Somatic system b. Autonomic system56 CENTRAL NERVOUS SYSTEM 58 • The major regions of the central nervous system (CNS) are the cerebrum, cerebellum, and spinal cord • The CNS is covered by three connective tissue layers, the meninges, but contains very little collagen or fibrous tissue throughout its substance, making it relatively soft and easily damaged by injuries affecting its protective cranium or vertebral bones. • Many structural features of CNS tissues can be seen in unstained, freshly dissected specimens. CENTRAL NERVOUS SYSTEM • Brain • Cerebellum • Medulla spinalis Cortex – Gray matter Medulla – White matter Gray matter & white matter Nervous system • The entire CNS displays organized areas of white matter and gray matter, differences caused by the differential distribution of myelin. The main components of white matter are myelinated axons, often grouped together as tracts, and the myelinproducing oligodendrocytes. • White matter contains astrocytes and microglia. Gray matter contains abundant neuronal cell bodies, dendrites, the initial unmyelinated portions of axons, astrocytes, and microglial cells. CNS IN THE MICROSCOPE • Gray matter ▫ Nerve cell bodies ▫ Glial cells (except fibrous astrocytes) ▫ Blood vessels • White matter ▫ Miyelinated axons ▫ Glial cells (except protoplasmic astrocytes) ▫ Blood vessels • Ventricules or central canal BRAIN (CEREBRUM) • 1500 gr. • Gyri / sulci • 2400 cm2 • 70-80 % water • 20-30 % protein & fat Gray matter: Cortex, Substansia grisea 1,5-4 mm thick White matter: Medulla, Substansia alba, CEREBRAL CORTEX • Responsible for • Learning • Memory • Information analysis • Initiation of motor response • Integration of sensory signals • Divided into six layers with neurons exhibiting a morphology unique to the particular layer CEREBRAL MEDULLA (White Matter) • Myelinated and unmyelinated axons • Capillaries • Neuroglial cells CEREBELLUM ¨ 150 gr (1/8-1/10 of adult brain) ¨ In baby 1/20 of weight of brain CEREBELLUM • Piamater • Outer – cortex • Molecular layer • Purkinje layer • Granular layerInner • Medulla CEREBELLAR CORTEX Responsible for: • Maintanance of balance and equilibrium • Maintanance of muscle tone • Coordination of skletal muscles CEREBELLUM • The cerebellar cortex is convoluted with many distinctive small folds, each supported at its center by tracts of white matter in the cerebellar medulla • Each fold has distinct molecular layers (ML) and granular layers • 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. CEREBELLAR CORTEX 2. Purkinje cell layer 1. Molecular Layer • Purkinje cell • Stellate cells • Dendrites of Purkinje cells 3. Granular layer • Small granule cells • Golgi cells • Neuroglial cells • Glomeruli (synaptic places bw granule cells & axons entering cerebellum) • Mossy fibers • Basket cells • Neuroglial cells • Unmyelinated axons from granular layer (Clinging fibers) 71 CEREBELLAR MEDULLA • Afferent fibers • Miyelinated, unmyelinated • Efferent fibers • Miyelinated, unmyelinated • Intermediate fibers • Miyelinated, unmyelinated • Neuroglial cells • Nuclei • • • • Corpus dentatum Nucleus emboliformis Nucleus fastigii Nucleus globosus SPINAL CORD • Length 40-45 cm • Diameter 1cm • Weight 30 gr • The spinal cord varies slightly in diameter along its length SPINAL CORD • In the vertebral canal • Occupy upper 2/3 of the vertebral canal • Extends from upper border of atlas to the lower border of L1 • Terminates in a slender filament of gray matter SPINAL CORD • Divisions; • Cervical • Thoracal • Lumbar • Sacral SPINAL CORD • Piamater • Outer white matter • Central butterfly-shaped gray matter • Centrally located “central canal” lined by ependymal cells SPINAL CORD GRAY MATTER • • • • Neurons Processes of neurons Neuroglial cells Blood vessels WHITE MATTER • Myelinayed & unmyelinated axons • Neuroglial cells • Blood vessels • Most of the nerve fibers are longitudinally arranged SPINAL CORD 79 (T1 - L2) SYMPATHETIC DIVISION (BRAIN, S2 - 4) PARASYMPATHETIC DIVISION AUTONOMIC NERVOUS SYSTEM SYMPATHETIC SYSTEM THOROCOLUMBAR SYSTEM (T1 - L2) PARASYMPATHETIC SYSTEM CRANIOSACRAL SYSTEM (BRAIN, S2 - 4) Enteric nervous system MEISSNER’S (SUBMUCOSAL) PLEXUS 84 AUERBACH’S (MYENTERIC) PLEXUS 85 Peripheral Nervous System (PNS) 86 PERIPHERAL NERVOUS SYSTEM Peripheral nerves – Cranial nerves (those emerge from brain) – Spinal nerves (those emerge from spinal cord) ▫ Ganglia: – Autonomic (sympathetic and parasympathetic) ganglia – Dorsal root (spinal or sensory) ganglia ▫ Receptors: – Interoceptive system – Exteroceptive system – Proprioceptive system ▫ 87 PERIPHERAL NERVES • Bundles of nerve fibers located outside the CNS, surrounded by connective tissue sheaths. • Most peripheral nerves are mixed, contain motor, sensory and sometimes autonomic fibers. 88 Myelinated Fibers • The plasma membrane of each covering Schwann cell fuses with itself around the axon, • Unlike oligodendrocytes of the CNS, a Schwann cell forms myelin around only a portion of one axon. • The multiple layers of Schwann cell membrane unite as a thick myelin sheath 89 • With high-magnification TEM, the myelin sheath appears as a thick electron-dense axonal covering in which the concentric membrane layers may be visible 90 Unmyelinated Fibers • In these unmyelinated fibers the glial cell does not form the multiple wrapping of a myelin sheath, unmyelinated fibers, each Schwann cell can enclose portions of many axons with small diameters. 91 Nerve Organization • In the PNS nerve fibers are grouped into bundles to form nerves. Except for very thin nerves containing only unmyelinated fibers, nerves have a whitish, glistening appearance because of their myelin and collagen content. • Axons and Schwann cells are enclosed within layers of connective tissue. 92 PERIPHERAL NERVE COVERINGS • Outside myelin coat nerve fibers are surrounded by; • Schwann cell coat • External lamina of the Schwann cell • Connective tissue layers – Endoneurium – Perineurium – Epineurium 93 ENDONEURIUM • Thin loose connective tissue rich in reticular fibers • Mast cells, macrophages and a few fibroblasts are present • Surrounding individual fibers. • In contact with basal lamina (external lamina) of Schwann cell 94 PERINEURIUM • Dense irregular connective tissue • Surrounds a group of fibers (fascicles) • Specialized to contribute to bloodnerve barrier • One or more cell layers thick 95 PERINEURIUM • Perineurial cells are squamous, contractile containing actin filaments • Possess receptors, transporters and enzymes that provide the active transport of substances. • Create a protective barrier 96 PERINEURIUM • In thick perineurium (5-6 layers), collagen fibrils are present in between perineurial cell layers but fibroblasts are absent 97 EPINEURIUM • Dense irregular connective tissue • Surrounds the entire nerve from outside 98 PERIPHERAL NERVES • Peripheral nerves establish communication between centers in the CNS and the sense organs and effectors (muscles, glands, etc). They generally contain both afferent and efferent fibers. • Afferent fibers carry information from internal body regions and the environment to the CNS. • Efferent fibers carry impulses from the CNS to effector organs commanded by these centers. • Nerves possessing only sensory fibers are called sensory nerves; those composed only of fibers carrying impulses to the effectors are called motor nerves. • Most nerves have both sensory and motor fibers and are called mixed nerves, usually also with both myelinated and unmyelinated axons. 99 GANGLIA 100 GANGLIA • Aggregations of cell bodies of neurons located outside the CNS • Surrounded by a connective tissue capsule • Associated with peripheral nerves. • Ganglion cells • Satellite cells • Blood vessels • Nerve fibers 101 GANGLION CELLS & SATELLITE CELLS 102 GANGLIA Spinal ganglia Sensory ganglia: 1. i. Dorsal root ganglia (Spinal Ganglia) ii. Ganglia associated with cranial nerves (V, VII, VIII, IX, X) Autonomic ganglia 2. i. ii. Sympathetic chain ganglia • Paravertebral • Prevertebral Parasympathetic ganglia (=İntramural = terminal gang.) Sympathetic ganglia Parasympathetic ganglia 103 1. SENSORY GANGLIA (Cranio-spinal ganglia) • Sensory ganglia receive afferent impulses that go to the CNS. • Contain cell bodies of sensory neurons, not synaptic stations I. Dorsal root ganglia (Spinal Gangliyon) II. Ganglia associated with cranial nerves (V, VII, VIII, IX, X) i. Trigeminal gang.= Semilunar gang. = Gasser gang. (V) ii. Genikulat gang. (VII) 104 1. SENSORY GANGLIA (Cranio-spinal ganglia) • Ganglionic cells: large pseudounipolar neuron cell bodies • Satellite cells: glial cells of ganglia arranged around the cell bodies of neurons • Nerve fibers • Little connective tissue containing blood vessels • relay information from the ganglion’s nerve endings to the gray matter of the spinal cord via synapses with local neurons. 105 2. AUTONOMIC GANGLIA Sympathetic Ganglia 1. 2. 3. Paravertebral (Sympathetic chain ganglia) Prevertebral Adrenal medulla (modified symp. gang., secretory cells of adrenal medulla innervated by cholinergic presynaptic sympathetic nerve fibers ) Parasympathetic Ganglia 1. Head ganglia • • • • 2. Ciliary ganglion (III) Submandibular ganglion (VII) Pterygopalatine ganglion (VII) Otic ganglion (IX) Terminal ganglia • • Submucosal plexus (Meissner’s plexus) Myenteric plexus (Auerbach’s plexus) Contain cell bodies of autonomic (postsynaptic) neurons, synaptic 106 stations 2. AUTONOMIC GANGLIA • House cell bodies of postganglionic autonomic nerves • Ganglionic cells; gradually smaller multipolar neuron cell bodies, motor in function • Scattered satellite cells • Nerve fibers • Little connective tissue containing blood vessels 107 SYMPATHETIC GANGLIA 108 PERIPHERAL NERVE ENDINGS • Terminals of axons which transmit impulses from the CNS to • Skeletal & smooth muscles (motor endings) • Glands (secretory endings) • Terminals of dendrites called Sensory endings or receptors which perceive stimuli & transmit this sensory input to the CNS 1. Exteroreceptors 2. Proprioreceptors 3. Interoreceptors 109 NERVE ENDINGS IN THE MUSCLE • Striated Muscle • Neuromuscular junction • Smooth Muscle • Free nerve endings • Cardiac muscle • Free nerve endings 110 Nerve endings in the exocrine glands 111 PERIPHERAL RECEPTORS 1. Mechanoreceptors Respond to touch 2. Thermoreceptors Respond to cold & warmth 3. Nociceptors Respond to pain due to mechanical stress, extremes of temperature differences chemical substances 112 & FREE NERVE ENDINGS q Epidermis q Around hair follicle 113 PERIPHERAL RECEPTORS 114 NERVE DEGENERATION AND REGENERATION 115 NERVE DEGENERATION AND REGENERATION 116 NO REGENERATION 117 NO REGENERATION IN CNS • No endoneurium, no neurolemmal sheat, • No nerve growth factor • Injured cells phagocytosed by microglia, space occupied by proliferation glial cells. Glial scar tissue. • Neurons don’t divide • Neural stem cells can be activated 118 119