INP_29.4.2024.pdf

(a) The membrane potential as it changes in time during an action potential. (b) The inward currents through three representative voltage gated sodium channels. Each channel opens with little delay when the membrane is depolarized to threshold. The channels stay open f...

(a) The membrane potential as it changes in time during an action potential. (b) The inward currents through three representative voltage gated sodium channels. Each channel opens with little delay when the membrane is depolarized to threshold. The channels stay open for no more than 1 ms and then inactivate. (c) The summed Na current flowing through all the sodium channels. (d) The outward currents through three representative voltage gated potassium channels. The high potassium permeability causes the membrane to hyperpolarize briefly. When the voltage-gated potassium channels close, the membrane potential relaxes back to the resting value, around 65 mV. (e) The summed K current flowing through all the potassium channels. (f) The net transmembrane current during the action potential. 13 FIGURE 4.12, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear Action potential Review Threshold : Threshold is the membrane potential at which enough voltage-gated sodium channels open so that the relative ionic permeability of the membrane (g) favors sodium over potassium. Rising phase: When the inside of the membrane has a negative electrical potential, there is a large driving force on Na. Therefore, Na rushes into the cell through the open sodium channels, causing the membrane to rapidly depolarize. Overshoot : Because the relative permeability of the membrane greatly favors sodium, the membrane potential goes to a value close to E Na which is greater than 0 mV. 14 Action potential Review … Falling phase : The behavior of two types of channels contributes to the falling phase. First, the voltage-gated sodium channels inactivate. Second, the voltage- gated potassium channels finally open (triggered to do so 1 ms earlier by the depolarization of the membrane). There is a great driving force on K when the membrane is strongly depolarized. Therefore, K rushes out of the cell through the open channels, causing the membrane potential to become negative again. Undershoot: The open voltage-gated potassium channels add to the resting potassium membrane permeability. Because there is very little sodium permeability, the membrane potential goes toward EK , causing a hyperpolarization relative to the resting membrane potential until the voltage-gated potassium channels close again. 15 Action potential … Absolute refractory period : Sodium channels inactivate when the membrane becomes strongly depolarized. They cannot be activated again, and another action potential cannot be generated, until the membrane potential becomes sufficiently negative to deactivate the channels. Relative refractory period : The membrane potential stays hyperpolarized until the voltage-gated potassium channels close. Therefore, more depolarizing current is required to bring the membrane potential to threshold. 16  The effect of injecting positive charge into a neuron (a) The axon hillock is impaled by two electrodes, one for recording the membrane potential relative to ground and the other for stimulating the neuron with electrical current. (b) When electrical current is injected into the neuron(top trace), the membrane is depolarized sufficiently to fire action potentials (bottom trace). 5 FIGURE A,Box4.3 , Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  Recording passive and active electrical signals in a nerve cell 1 If injected current does not depolarize the membrane to threshold, no action potentials will be generated. 2 if injected current depolarizes the membrane beyond threshold, action potentials will be generated. 3 The action potential firing rate increases as the depolarizing current increases (A) Two microelectrodes are inserted into a neuron; one for stimulate and another for recording. (B) Inserting the voltage-measuring microelectrode into the neuron (bottom) reveals a negative potential, the resting membrane potential. Injecting current through the other microelectrode (top) alters the neuronal membrane potential. Hyperpolarizing current pulses produce only passive changes in the membrane potential. While small depolarizing currents also elicit only passive responses, depolarization that cause the membrane potential to meet or exceed threshold additionally evoke action potentials. 6  Electrical Conduction (Passive conduction) If this current pulse is below the threshold for generating an action potential, then the magnitude of the resulting potential change will decay with increasing distance from the site of current injection.Typically, the potential falls to a small fraction of its initial value at a distance of no more than a few millimeters away from the site of injection. Passive conduction decays over distance (A) Experimental arrangement for examining passive flow of electrical current in an axon. A current- passing electrode produces a current that yields a subthreshold change in membrane potential, which spreads passively along the axon. (B) Potential responses recorded by microelectrodes at the positions indicated. With increasing distance from the site of current injection, the amplitude of the potential change is attenuated as current leaks out of the axon. (C) Relationship between the amplitude of potential responses and distance. 20 FIGURE 2.3, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  Electrical Conduction (Active conduction) The ability of action potentials to boost the spatial spread of electrical signals can be seen if the experiment is repeated with a depolarizing current pulse that is large enough to produce an action potential. In this case, the result is dramatically different. Now an action potential of constant amplitude is observed along the entire length of the axon. The fact that electrical signaling now occurs without any decrement indicates that active conduction via action potentials is a very effective way to circumvent the inherent leakiness of neurons. (D) If the experiment shown in (A) is repeated with a supra threshold current, an active response, the action potential, is evoked. (E) Action potentials recorded at the positions indicated by microelectrodes. The amplitude of the action potential is constant along the length of the axon, although the time of appearance of the action potential is delayed with increasing distance. (F) The constant amplitude of an action potential (solid black line) measured at different distances. 21 FIGURE2.3, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  saltatory conduction Myelinated nerve fibres are covered by an insulating sheath of myelin, interrupted every few milli meters by spaces known as the nodes of Ranvier, where the fibre is exposed to the extracellular fluid. the primary function of oligodendroglial and Schwann cells is providing layers of membrane that insulate axons. For example, oligodendroglia are found only in the central nervous system (brain and spinal cord),Schwann cells are found only in the peripheral nervous system (parts outside the skull and vertebral column). One oligodendroglial cell contributes myelin to several axons, whereas each Schwann cell myelinates only a single axon 9 FIGURE 2.27, Figure2.27, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  saltatory conduction … Sites of excitation and changes of membrane permeability exist only at the nodes. current flows by jumping from one node to the next in a process known as saltatory conduction. Voltage-gated sodium channels are concentrated in the axonal membrane at the nodes of Ranvier 10 FIGURE 4.15, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  spike-initiation zone As a rule, the membranes of dendrites and neuronal cell bodies do not generate sodium-dependent action potentials because they have very few voltage-gated sodium channels. Only membrane that contains these specialized protein molecules is capable of generating action potentials, and this type of excitable membrane is usually found only in axons. Therefore, the part of the neuron where an axon originates from the soma, the axon hillock, is often also called the spike- initiation zone. In a typical neuron in CNS, the depolarization of the dendrites and soma caused by synaptic input from other neurons leads to the generation of action potentials if the membrane of the axon hillock is depolarized beyond threshold. In most sensory neurons, however, the spike-initiation zone occurs near the sensory nerve endings, where the depolarization caused by sensory stimulation leads to the generation of action potentials that propagate along the sensory nerves. The spike-initiation zone. Membrane proteins specify the function of different parts of the neuron. (A) Cortical pyramidal neuron. (B) Primary sensory neuron. Despite the diversity of neuronal structure, the axonal membrane can be identified at the molecular level by its high density of voltage-gated sodium channels. This molecular distinction enables axons to generate and conduct action potentials. The region of membrane where action potentials are normally generated is called the spike-initiation zone. The arrows indicate the normal direction of action potential propagation in these two types of neuron. 11 FIGURE 4.16, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  synaptic transmission … The actions of psychoactive drugs, the causes of mental disorders, the neural bases of learning and memory—indeed, all the operations of the nervous system—cannot be understood without knowledge of synaptic transmission. Solid support for the concept of chemical synapses was A B provided in 1921 by Otto Loewi. Vagus nerve (Decrease heart rate) Loewi showed that electrical stimulation of axons innervating the frog’s heart caused the release of a chemical that could Otto Loewi mimic the effects of neuron stimulation on the heartbeat. 1 Stimulate 2 3 Later, Bernard Katz and his colleagues at University College vagus Collect fluid Add fluid to London conclusively demonstrated that fast transmission at sample recipient heart the synapse between a motor neuron axon and skeletal muscle was chemically mediated. Heart A Heart B  Electrical Synapse The existence of such electrical synapses was finally proven in the late 1950s by Edwin Furshpan and David Potter. Electrical synapses are relatively simple in structure and function, and they allow the direct transfer of ionic current from one cell to the next. Electrical synapses occur at specialized sites called gap junctions. Transmission at electrical synapses is very fast. Thus, an action potential in the presynaptic neuron can produce, with very little delay, an action potential in the postsynaptic neuron. Fig5.1, Neuroscience, six edition ,Edited by Dale Purves  Electrical Synapse… At a gap junction, the membranes of two cells are separated by only about 3 nm, and this narrow gap is spanned by clusters of special proteins called connexins. Six connexin subunits combine to form a channel called a connexon , and two connexons (one from each cell) meet and combine to form a gap junction channel. The channel allows ions to pass directly from the cytoplasm of one cell. Most gap junctions allow ionic current to pass equally well in both directions; therefore, unlike the vast majority of chemical synapses, electrical synapses are bidirectional. Because electrical current (in the form of ions) can pass through these channels, cells connected by gap junctions are said to be electrically coupled. They are often found where normal function requires that the activity of neighboring neurons be highly synchronized. FIGURE 5.1, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  Electrical synapses. (a) A gap junction interconnecting the dendrites of two neurons constitutes an electrical synapse. (b) An action potential generated in one neuron causes a small amount of ionic current to flow through gap junction channels into a second neuron, inducing an electrical PSP. (Source: Part a from Sloper and Powell, 1978.) FIGURE 5.2, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  Chemical Synapses Fig5.4, Neuroscience, six edition ,Edited by Dale Purves  Excitatory Post Synaptic Potential The generation of an EPSP (a) An action potential arriving in the presynaptic terminal causes the release of neurotransmitter. (b) The molecules bind to transmitter-gated ion channels in the postsynaptic membrane. If Na enters the postsynaptic cell through the open channels, the membrane will become depolarized. (c) The resulting change in membrane potential (Vm), as recorded by a microelectrode in the cell, is the EPSP. FIGURE 5.15, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  Inhibitory Post Synaptic Potential The generation of an IPSP. (a) An action potential arriving in the presynaptic terminal causes the release of neurotransmitter. (b) The molecules bind to transmitter-gated ion channels in the postsynaptic membrane. If Cl enters the postsynaptic cell through the open channels, the membrane will become hyperpolarized. (c) The resulting change in membrane potential (Vm), as recorded by a microelectrode in the cell, is the IPSP FIGURE 5.16, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear  Summation of postsynaptic potentials (A) A microelectrode records the postsynaptic potentials produced by the activity of two excitatory synapses (E1 and E2) and an inhibitory synapse (I). (B) Electrical responses to synaptic activation. Stimulating either excitatory synapse (E1 or E2) produces a subthreshold EPSP, whereas stimulating both synapses at the same time (E1 + E2) produces a supra threshold EPSP that evokes a postsynaptic action potential (shown in blue). Activation of the inhibitory synapse alone (I) results in a hyperpolarizing IPSP. Summing this IPSP (dashed red line) with the EPSP (dashed yellow line) produced by one excitatory synapse (E1 + I) reduces the amplitude of the EPSP (solid orange line), while summing it with the supra threshold EPSP produced by activating synapses E1 and E2 keeps the postsynaptic neuron below threshold, so that no action potential is evoked.  EPSP summation. (a) A presynaptic action potential triggers a small EPSP in a postsynaptic neuron. (b) Spatial summation of EPSPs: When two or more presynaptic inputs are active at the same time, their individual EPSPs add together. (c) Temporal summation of EPSPs: When the same presynaptic fiber fires action potentials in quick succession, the individual EPSPs add together FIGURE 5.19, Neuroscience, exploring the brain, Fourth edition ,Edited by M.F Bear