Lesson 12 - Nervous Tissue (I) - Cytology and Histology PDF

Cytology and Histology LESSON 12 NERVOUS TISSUE (I) The neuron and the synapsis The organism of higher vertebrates is related to the internal and the external environments through the functions carried out by its own tissues. The functions of the nervous tissue are (1) to receive and transmit stim...

Cytology and Histology LESSON 12 NERVOUS TISSUE (I) The neuron and the synapsis The organism of higher vertebrates is related to the internal and the external environments through the functions carried out by its own tissues. The functions of the nervous tissue are (1) to receive and transmit stimuli and (2) to integrate and associate information (reception, analysis of stimuli and elaboration of an adequate response). Accordingly, the nervous tissue needs a large contact surface (extension, processes, synapses). The specific properties of nervous tissue are irritability and conductivity. Irritability or excitability is the ability to react to a stimulus. Conductivity is the ability to transport the response to the effector organ, which can be another neuron, a muscle fibre, a gland, etc. The nervous tissue has an ectodermal origin, specifically the neuroectoderm or neuroepithelium, which undergoes thickening and forms the neural plate. The neural plate gives rise to (1) the neural tube and (2) the neural crest cells. Nervous tissue is distributed throughout the body and is mainly made up of cells: neurons and neuroglial cells (Figure 1). There are about 50 times more neuroglial cells than neurons in the nervous tissue of vertebrates (Figure 2). NEURON MICROGLIA NERVOUS CELLS Neurons EPENDIMOCYTE PROTOPLASMIC ASTROCYTE Neuroglial cells Neuropil FIBROUS ASTROCYTE OLIGODENDROCYTES Figure 1. Schematic representation of neurons and neuroglial cells. Figure 2. Nervous tissue made up of nervous cells (neurons and neuroglial cells) and neuropil. Cytology and Histology I. THE NEURON 1. Components There are two main components: the neuronal body or soma, also known as perikaryon (although this term actually refers to the cytoplasm of the neuron) and the neuronal processes, which are the dendrites and the axon (Figure 3). The neuronal body or soma consists of the cell membrane, nucleus, and perikaryon or cytoplasm. Figure 3. Scheme of the components of a neuron. 2. The neuronal body or soma It has a variable size between 4 and 135 µm and morphologically it is usually polygonal (stellate), although it can present different shapes depending on its location. Substances that travel distally through the axon and dendrites are synthesized in the cytoplasm. The region of the cytoplasm where the axon originates is called the axon hillock. The cell membrane is the same as that of any other cell except at the synapsis level. The nucleus is usually large, central and single, with a prominent nucleolus and a predominance of dispersed chromatin (euchromatin). The neuronal cytoplasm is responsible for producing structural proteins (e.g. for tubules and microfilaments), membrane proteins (e.g. for ion channels) and enzymes (e.g. for glucose metabolism and synthesis of secretion products). In the perikaryon we can observe: - Nissl bodies (chromatophilic substance): They correspond to RER, free ribosomes and polysomes, which give the cytoplasm its basophilic and granular appearance. They are more abundant in large neurons (motoneurons) than in small ones. They are found in the perikaryon and dendrites and are not found in the axon or axon hillock. Staining: blue colour with toluidine blue. Function: protein synthesis. - SER: can be found in the soma, in the dendrites and in the axon. - Golgi complex: which gives rise to secretory and synaptic vesicles and is more developed in secretory neurons. - Mitochondria, very abundant, especially in the terminal axon. They are shaped like a filament or rod and their cristae are longitudinally oriented. They are constantly moving in the cytoplasm. Cytology and Histology - Cytoskeletal filaments: neurotubules (23-25 nm in diameter) are disordered along the cytoplasm of the entire neuron and are related to the rapid transport of organelles within the neuron; and neurofilaments (10 nm) (structural support function) that are disordered in the perikaryon and arranged in the dendrites and axon. - Inclusions: such as lipofuscin and melanin, lipids or secretion granules. 1) Lipofuscin is a terminal product of lipid and protein degradation (lysosomes, autophagosomes) and is located in the perikaryon and dendrites. It increases with age and cell wear (wear pigment), or in some diseases. 2) Melanin is normally found in locations such as the Substantia nigra of the midbrain, locus ceruleus or in the leptomeninges of dark-coloured coat animals. It accumulates with age. 3) Secretion granules, present in neurosecretory neurons. 3. Neuronal processes Dendrites (dendron = tree) are multiple neuronal processes of decreasing diameter. They increase the surface of the neuron. The membrane may have lateral processes called dendritic “thorns”, which increase its surface area. They are the places where synapses are “received” (synaptic contact point) (Figure 4). The cytoplasm has Nissl bodies, especially at the beginning; the rest of the organelles decreases in quantity as we move away from the soma. The axon is a single, long, thin and smooth prolongation of uniform diameter. It has the following parts: (1) the implantation cone or axon hillock of the soma, (2) the initial segment, (3) the main segment (which may have collateral branches), and (4) the terminal arborization. Structurally, it is made up of the axolemma or membrane and the axoplasm or cytoplasm, which lacks Nissl bodies and has 80% proteins and 20% carbohydrates and lipids, SER in the periphery, very abundant mitochondria especially in the terminal portion, vesicles containing neurotransmitters and neurosecretory granules, lysosomes, and an ordered cytoskeleton. Axonal transport can be (1) anterograde or orthodromic spread, which is used by organoids, vesicles, macromolecules (actin, myosin, clathrin), and enzymes necessary for the synthesis of neurotransmitters; and (2) retrograde or antidromic spread, medium speed, 200300 mm/day; which is the one used by the proteins of the neurofilaments and microtubules as well as the material introduced by endocytosis (for example, remains of the membrane and of neurotransmitters, or toxins and viruses, such as tetanus toxin or rabies virus). 4. Classification of neurons A) Depending on how do they perform their function: releasing neurotransmitters or secreting hormones. 1) Conduction or transmission neurons: They are the majority of neurons. They have a body and extensions. They release neurotransmitters at synapses. According to their distribution, they can be: unipolar, with a single prolongation (e.g. amacrine neurons of the retina, and olfactory neurons); bipolar, with two processes, the cell body being intercalated in the axon (e.g. bipolar neurons of the retina); pseudounipolar, with a bifurcation process that acts as a dendrite and an axon (e.g. sensory neurons of the spinal ganglia); and multipolar, with a dendritic tree and an axon (motoneurons and interneurons) (Figure 5). Cytology and Histology RECEPTION AREA BIPOLAR CONDUCTION AREA UNIPOLAR EFFECTOR AREA MULTIPOLAR Figure 4. Function of the different components of the neuron. Figure 5. Types of conduction or transmission neurons. 2) Neurosecretory neurons: They are specialized in secreting substances, transporting them along the axon and releasing them into the blood in the neurohemal organs (e.g., neurons of the hypothalamus that produce oxytocin, antidiuretic hormone, and hypothalamic releasing or inhibiting factors). B) According to their function: sensory (afferent), interneurons or motoneurons (efferent). - Sensory neurons: receive sensory input at their dendritic terminals and conduct impulses to the CNS for processing. - Interneurons: located completely in the CNS, function as interconnectors that establish networks between sensory and motoneurons and other interneurons. - Motoneurons: originate in the CNS and conduct their impulses to muscles, glands and other neurons. II. NERVOUS FIBRE The axon plus its sheaths is called nerve fibre. However, the whole axon is not surrounded by sheaths, being able to identify sheathed axons and bare axons, which correspond with Nodes of Ranvier. When we consider the whole nerve fibre, its envelope can be of two types:  With cells and with myelin: myelinated nerve fibre (cell sheath + myelin sheath)  With cells and without myelin: unmyelinated nerve fibre (only has cell sheath) The myelinated nerve fibre is found in both the CNS and the PNS. However, there are differences between them. Thus, in CNS, the cell sheath is made of oligodendrocytes, and in PNS, the cell sheath is made of Schwann cells. Furthermore, the oligodendrocyte lacks a basement membrane, whereas the Schwann cell is surrounded by a basement membrane. While each oligodendrocyte surrounds several internodes in different nerve fibres at once, each Schwann cell surrounds only one internode of an axon. Cytology and Histology Unmyelinated nerve fibre is found in some parts of the ANS. It only has a cell sheath, being the Schwann cells which form it. Each Schwann cell surrounds several axons, but in this case without producing myelin. Cytology and Histology 1. Myelin Myelin is a lipoprotein substance in the form of sheets or layers around the axon. This substance is formed by oligodendrocytes in the CNS and Schwann cells in the PNS. Each oligodendrocyte can form the myelin covering 1 to 60 internodes of different axons, while each Schwann cell produces myelin for a single internode from an axon (Figure 6A and B). A B Figure 6. Nerve fibre formation diagram in the CNS (A) and in the SNP (B). Although it appears to surround the axon along its entire length, there are four areas where the axon of the myelinated fibres is not covered by myelin: (1) the implantation cone or axon hillock, (2) the initial segment, (3) the nodes of Ranvier and (4) the synapsis. The nodes of Ranvier are the parts of the axon that remain between the cell and the Schwann cell, that is, the space between two sections of the myelin sheath and that are not covered by it. They are true dilations of the axon due to the reduction of the external pressure exerted at that point by the cell sheath due to the local lack of myelin sheath. The synapsis is the site through which the nerve impulse is transmitted from one neuron to another cell. When fresh, myelin is a shiny, whitish substance that is responsible for the white colour of the white matter in the nervous system. Myelin is made up of different types of lipids (phospholipids, cerebrosides and cholesterol) and neurokeratin, which is the only thing that remains of myelin once it has been treated with alcohol for study under a light microscope. The most specific technique for visualizing myelin is osmium impregnation. Myelin is formed by spiraling around the axon membrane structures that synthesize oligodendrocytes in the CNS and Schwann cells in the PNS (one to 50 turns in a spiral). Thus, ultrastructurally, the myelin sheath is characterized by presenting:  Major and minor dense lines: correspond to the coincidence of the internal and external faces of the membrane of the producer cells.  Incisures or clefts of Schmidt - Lanterman: these are openings in the dense lines that allow the flow of intracellular material through the myelin sheath. The main function of myelin is electrical isolation (the action potential jumps from node to node of Ranvier, rather than continually progressing as in unmyelinated axons, increasing the speed of conduction). The jumping mechanism, called saltatory conduction, is much faster than the conduction through unmyelinated fibres. Cytology and Histology Schwann cell Myelin sheath A B Figure 7. Transmission electron microscope photograph showing the major and minor dense lines of the myelin sheath (A), and myelinated nerve fibre of the SNP (B). 2. The synapsis or synapse The synapsis is the site where the nerve impulse is transmitted from a presynaptic cell (neuron) to another postsynaptic cell (another neuron, a muscle cell, or a gland). When the cell that receives the nerve impulse is a neuron, the synapsis is called interneuronal. When the cell that receives the nerve impulse is not a neuron, the synapsis is called a neuroeffector. Interneuronal synapses can be of different types depending on the structures of both involved neurons: axodendritic, axosomatic and axoaxonic; but also dendrodendritic, dendrosomatic, somatodendritic and somatosomatic. Neuroeffector synapses may or may not be given specific names. Thus, the neuromuscular synapsis (between a neuron and skeletal muscle fibres) is called the motor endplate. Figure 8. Diagram of interneuronal synapses. Figure 9. Neuromuscular synapsis (motor endplate) under the electron microscope. Cytology and Histology Depending on the vehicle through which the transmission of the nerve impulse occurs, there are two different types of synapses:  The electrical synapsis, in which electrical current is transmitted from one cell to another through the direct passage of ions through communicating junctions between them called connexons. The electrical synapsis is exclusively interneuronal, and very rare: brain stem, retina, cerebral cortex.  The chemical synapsis, in which different chemical substances act as intermediaries in the transmission of electrical current. These chemicals are generically called neurotransmitters. This type of synapsis is much more frequent than the electrical one and can be both interneuronal and neuroeffector. The chemical synapsis has three parts: (1) the presynaptic part (2) the central part or synaptic cleft, and (3) the postsynaptic part. In summary, the presynaptic part contains neurotransmitters within vesicles, which are released into the space between the two cells called the synaptic cleft, where the neurotransmitters bind to receptors on the postsynaptic cell membrane, receptors that open ion channels. Depending on the ion channels that are opened, the synapsis will be excitatory or inhibitory. 3. Morphology of the chemical synapsis The presynaptic part is a specialized area of the axon of the neuron that transmits the nerve impulse and is called the synaptic button. The synaptic button can be located at two levels:  In the final portion of the axon, in which case it is called the terminal synaptic button.  Along the axon, in which case it is called the synaptic button on passage The synaptic button, whether terminal or on passage, has the following elements:  In the cytoplasm: mitochondria, a few elements of the smooth endoplasmic reticulum, actin microfilaments, and many vesicles located next to the plasma membrane. They are called synaptic vesicles, measure 40 to 60 nm in diameter, and are packed with neurotransmitters. Some synaptic vesicles are located next to the plasma membrane, to which they are attached by proteins such as synaptophysin, and others are further away from it, attached to actin microfilaments by other proteins, such as synapsin I.  In the plasma membrane: focal thickenings of the protein layer on the cytoplasmic side of a conical shape. It is the active site of the synapse, that is, the point where the synaptic vesicles will empty their contents by exocytosis to the synaptic cleft. The synaptic cleft is the space between the pre- and post- synaptic membranes. This space is between 12 and 30 nm wide and is occupied by the microenvironment of the cells, composed of glycosaminoglycans that are PAS-positive. In addition, this Cytology and Histology gap is completed by intersynaptic filaments or thin structures of protein nature that cross the gap without defined morphology and that join both membranes. The postsynaptic part (it is in the cell that receives the nerve impulse: neuron, muscle, gland) has a thickening at the membrane level that contains receptors for neurotransmitters. The thickening is at the level of the inner protein layer and, at the level of the cytoplasm, by electrondense material. 3. Types of neurotransmitters - According to their mechanism of action:  Neurotransmitters: directly related to ion channels, that is, those that open sodium channels.  Neuromodulators and Neurohormones: they activate a second messenger, being related to the G proteins or receptor kinases. - According to their nature: 1) Small molecules, 2) Neuropeptides, 3) Gases. 4. Summary of chemical synapsis production - The synapsis is activated by the arrival of an action potential that depolarizes the presynaptic element. - The membrane channels of the presynaptic element open to allow the entry of calcium ions. - The elevation of cytoplasmic calcium triggers the fusion of the synaptic vesicles with the presynaptic membrane, releasing neurotransmitter or neuromodulatory molecules by exocytosis; These molecules diffuse through the synaptic cleft and bind to membrane receptors on the postsynaptic element. As a result of this, ion channels are opened or closed in the postsynaptic membrane, or membrane receptors are modified. At excitatory synapses, there is a simultaneous increase in permeability for sodium and potassium ions and this leads to depolarization of the postsynaptic membrane. At inhibitory synapses, the permeability for potassium and chloride ions increases and this distances the membrane potential from its excitation threshold. - Synaptic activity stops when enzymes degrade neurotransmitter molecules in the membrane of the postsynaptic element; degradation products are collected by the presynaptic element for synthesis of the new neurotransmitters, through a receptor-mediated endocytosis process.