Neurophysiology PDF

Chapter 1: Neurophysiology Introduction The parenchyma of nervous tissue consists of neurons and supporting cells called neuroglia. The nervous tissue forms the nervous system, which can be divided into the central nervous system and the peripheral nervous system. The central nervous syste...

Chapter 1: Neurophysiology Introduction The parenchyma of nervous tissue consists of neurons and supporting cells called neuroglia. The nervous tissue forms the nervous system, which can be divided into the central nervous system and the peripheral nervous system. The central nervous system (CNS) consists of the brain and spinal cord. The peripheral nervous system (PNS) consists of the cranial and spinal nerves, including associated nerve roots and ganglia. The nerves and ganglia that innervate the viscera are called the autonomic nervous system. I/ Physiology of the neuron A. Structure of the neuron Neurons are the structural and functional units of the nervous system (Fig. 1). Neurons specialize in excitability and communicate by releasing chemicals (neurotransmitters, neuromodulators, or neurohormones). Excitation involves the passage of ions through protein channels embedded in the neuronal plasma membrane that otherwise acts as a hydrophobic barrier to ion flow. By chemical secretion, neurons transmit excitation to other neurons or to muscles or glands. Figure1. Schematic representation of a typical (multipolar) neuron. Functional classification There are 03 types (Fig. 2): Sensory neurons: carry nerve impulses to the CNS. Somatic sensory: conduct impulses that come from receptors in the skin, bones, muscles and joints. Visceral sensitive: conduct the impulses that come from the viscera. Motor neurons: conduct impulses from the CNS. Somatic motors: innervate skeletal muscles. Visceral motors: innervate the cardiac muscle, vascular smooth muscles and glands. Association neurons (interneurons): conduct impulses from sensory neurons to motor neurons. Figure 2. Types of functional classification of neurons 1  B. Membrane potential The neuron membrane is polarized.This polarization is due to the existence of a concentration gradient of sodium and potassium on either side of the plasma membrane. At rest, this concentration gradient is maintained by the Na-K-ATPase pump and creates a resting potential of -70 mV. 1. Resting potential The resting potential is the membrane potential of an excitable cell when it is at rest.It is always negative. The resting potential of neurons is particularly remarkable because it is its modification that allows the transmission, propagation and integration of signals at the cerebral level. Heis therefore the result of passive transport but also of active transport of ions between neuron and extracellular environment. Ionic origin of the resting potential This phenomenon is explained by adifference in membrane permeability, in particular, to Na+ and K ions +.The cell membrane is very permeable to K+ ions and much less permeable to Na+ ions: K+ carries inside and Na+ carries outside. 2. Action potential The action potential (AP) is a brief change in membrane potential (depolarizing) that propagates along a neuron to transmit information quickly and over a long distance through nerve pathways (axons of the neuron). The inside of the nerve cell is charged positively and the outside negatively. This change in polarity (which lasts 1 thousandth of a second) is called an action potential. Ionic origin of the action potential : Localized and transient charge inversion is due to the modification of membrane permeability to Na+ and K+ ions: massive entry of Na+, then exit of K+, this is the action potential or wave of negativity or even nerve impulse of the nerve fiber. C. Neuron excitability The action potential has several properties: 1. Excitation threshold The triggering of the action potential is dependent on the intensity of the electrical stimulation, i.e. the depolarization provoked. As long as the membrane potential of the neuron remains below a critical level (around -30 mV), nothing happens. But as soon as this value is reached or exceeded, i.e. the amplitude of the threshold depolarization exceeds 40 mV, the action potential appears. This action potential is triggered as soon as thegraduated potentialsdepolarizing agents reach a certain value. This threshold is dependent on voltage-gated sodium channels - Nav -. 2 2. All or Nothing Law This law is based on three processes: the existence of the trigger threshold, the feedback process of Na+ receptor opening; the existence of the Na+ equilibrium potential. 3. Law of Refractoriness (Refractory Period) This property is essential in the propagation of the action potential. It corresponds tothe period during which the nerve fiber becomes inexcitable following excitation.There is : 1. The absolute refractory periodcorresponds to the inability to trigger a 2nd action potential. 2. The relative refractory period, a period after the previous one, sometimes allows a 2nd action potential to be triggered, but of reduced amplitude. 4. Synaptic integration: spatial or temporal summation Spatial summation occurs when the postsynaptic neuron is stimulated at the same time by a large number of synaptic boutons belonging to the same neuron or, usually, to several different neurons. Temporal summation occurs when multiple stimulations occur within a very short period of time. 3 D. Neuron conductivity 1. Propagation mechanism of action potential The action potential is described in four phases (Fig. 5) : Figure 2. Representation of action potential 1. Stimulus starts the rapid change in voltage or action potential. In patch-clamp mode, sufficient current must be administered to the cell in order to raise the voltage above the threshold voltage to start membrane depolarization. 2. Depolarization is caused by a rapid rise in membrane potential opening of sodium channels in the cellular membrane, resulting in a large influx of sodium ions. 3. Membrane Repolarization results from rapid sodium channel inactivation as well as a large efflux of potassium ions resulting from activated potassium channels. 4. Hyperpolarization is a lowered membrane potential caused by the efflux of potassium ions and closing of the potassium channels. 5. Resting state is when membrane potential returns to the resting voltage that occurred before the stimulus occurred. 2. Velocity of conduction of nerve impulses The speed of the propagation of the influx depends on several parameters: the diameter of the axon, presence or absence of themyelin, the distance between thenodes of Ranvier. The action potential propagates over a long distance. In general, larger, myelinated axons conduct nerve impulses more quickly. 3. Direction of propagation or conduction of nerve impulses The message is one-way (Fig. 6): The neurotransmitters synthesized by a pre-synaptic neuron are stored in the vicinity of the terminal arborizations before being released into the synaptic space upon the arrival of action potentials.Neurotransmitter molecules bind to specific receptors carried by the post-synaptic membrane. Their binding causes a high permeability to the explosive entry of Na+ into the post-synaptic membrane, hence the appearance of action potentials in the membrane: the nerve message then continues its propagation. 4  Figure 3. Direction of propagation of the action potential Propagation of nerve impulses is of two types: Continuous conduction : In unmyelinated fibers, depolarization is progressive, each sodium channel reached by the AP opens and contributes to the propagation of the nerve impulse. Saltatory conduction: In myelinated fibers, the propagation of the nerve impulse is done by the generation of AP at each node of Ranvier (by jumping). The AP at each node creates a depolarization that reaches the next node. Conduction is then much faster and is called saltatory. II/ Synaptic transmission Synaptic transmission of nerve impulses from one neuron to anotheris done through a chemical substance called a chemical mediator or neurotransmitter or neuromediator. On the same neuron, there are synapses which allow the passage of nerve messages (excitatory synapses) and others which oppose each other (inhibitory synapses). Synapse and synaptic transmission constitute the anatomofunctional support of interneuronal communication. A. Synapse 1. Definition and Classification Interneuronal communication is ensured by a particular process, synaptic transmission, which involves the use of a specific anatomofunctional structure, the synapse. In the central nervous system, the synapse is an area of juxtaposition between neurons. In the peripheral nervous system, this juxtaposition can occur between a neuron on the one hand and a muscle or glandular cell on the other. 5  Synapses can communicate: two neurons (neuro-neuronal synapses), a neuron and another cell, muscular or glandular (neuroeffector synapses). According to their functional classification can be classified into: chemical synapses, very majority (around 99% of synapses), electrical synapses. Each axon ends in a synapse. The best-known chemical synapse is that between a motor neuron and a skeletal muscle cell: the neuromuscular synapse, also known as the neuromuscular junction (Fig. 7). Synaptic communication at the neuromuscular junction is fundamentally similar to that between neurons, although there is greater variety in the specifics of neuron-neuron synaptic transmission. The synaptic combination in the nervous system can be: Axo-axonic synapse, Dendro-dendritic synapse, Dendrosomatic synapse, Somato-dendritic synapse Somato-somatic synapse. Figure 4. Synapse between a motor neuron and a skeletal muscle fiber. 2. Morphology 6 B. Mechanisms of neurotransmission 1. Definition of neurotransmission Neurotransmission includes in order: the synthesis, storage and release of chemical messengers (transmitters) into the extracellular space; the reception of neurotransmitter information at the target cell; the transduction of this signal into another set of biochemical and voltage changes. 2. Release of neurotransmitter Synaptic transmission occurs in two stages: release of neurotransmitter from the presynaptic element then fixation of the neurotransmitter on the postsynaptic receptors. Each of these steps is, in fact, extremely complex and only the essential steps will be given. Stimulation of the nerve causes an AP that propagates to the axon terminal and causes the opening of sodium channels and voltage-gated calcium channels, concentrated at the release sites. This triggers a calcium influx and an exocytosis process:It is the emptying of the contents of a more or less significant number of synaptic vesicles, leading topresynaptic release of ACh. Calcium influx,caused by the opening of calcium channels under the influence of depolarization of the presynaptic terminal,is a consequence of the calcium concentration gradient between the extracellular and intracellular environments.This influx causes a suddenaccumulation of calcium in the presynaptic element, and increased intracellular calcium concentration, particularly at neurotransmitter release sites. Figure 5. Main stages of neurotransmission. 1: synthesis of the neurotransmitter; 2: neurotransmitter transport; 3: storage of vesicles containing the neurotransmitter; 4: transport of vesicles and docking in an active zone; 5: fusion of the vesicular membrane and the presynaptic plasma membrane; 6: the release (exocytosis) of the neurotransmitter which will diffuse (6a) into the synaptic cleft, bind (6b) to the postsynaptic receptors, be degraded (6c) in the synaptic cleft, or be recaptured (6d) by a transporter system and 7: the recycling of synaptic vesicles. 7  Table. The main neurotransmitters in the central nervous system 3. Post-synaptic potentials: PPSE and PPSI The postsynaptic potential (PSP) is a temporary variation in the membrane potential of a postsynaptic neuron: it is agraduated potential. This potential created in the postsynaptic cell, perhaps: either exciting, hence the nameexcitatory postsynaptic potential (EPSP), either inhibitors, henceinhibitory postsynaptic potential (IPSP)(Fig. 8). Figure 6. Results of electrical stimulation of a motor neuron 4. Fundamental properties of neurotransmission C. Particularities of synapses 1. Neuromuscular synapse (motor endplate) The neuromuscular junction is specialized for unidirectional synaptic communication.Motor neurons that connect to skeletal muscles have their cell bodies located in the central nervous system, either in the spinal cord or the brainstem. The axons of these motor neurons travel through peripheral nerves, toward the muscle, where each motor neuron synapses on several individual fibers (cells) of the muscle. However, an individual skeletal muscle fiber receives synaptic input from, and thus its contraction is controlled by, only one motor neuron. The neuromuscular junction, like most chemical synapses, has: (1) a presynaptic side; (2) a narrow space between the neuron and the muscle fiber, called the synaptic cleft; (3) a postsynaptic side (Fig. 9). 8  The presynaptic side of the synapse consists of the terminal part of the motor neuron called the synaptic bouton.The synaptic bouton contains a large number of storage vesicles, called synaptic vesicles, which contain the chemical neurotransmitter, in this case acetylcholine.These synaptic vesicles are aligned in rows along the inner surface of the terminal membrane (Fig. 8). The region of presynaptic membrane associated with each double row of vesicles is called the active zone and is the site where the synaptic vesicles will ultimately release acetylcholine into the synaptic cleft.The synaptic bouton also contains mitochondria, an indication of active metabolism in the cytoplasm. Some mitochondrial products (e.g., acetyl-CoA, ATP) play a role in the local synthesis of acetylcholine and its movement into synaptic vesicles. Figure 7. Neuromuscular junction 9