The Nervous System 2k24 PDF

The Nervous System Chapter 8 1  Chapter 8 Topics Organization of the nervous system Membrane potential and the electrical signals generated by neurons Cell-to-cell communication in the nervous system Integration of neural information transfer...

The Nervous System Chapter 8 1  Chapter 8 Topics Organization of the nervous system Membrane potential and the electrical signals generated by neurons Cell-to-cell communication in the nervous system Integration of neural information transfer 2 The Nervous System is Divided into Two Broad Divisions: 1. Central Nervous System (CNS) Brain and Spinal Cord 2. Peripheral Nervous System Ganglia (clusters of neuronal cells outside CNS) Nerves Sensory receptors and Sensory structures (ex. Eyes) Enteric nervous system located in walls of digestive tract 3  The role of the CNS: The CNS receives inputs from the sensory systems of the PNS & integrates these inputs, determines an appropriate response, and initiates and coordinates the response. Ex: Cerebral cortex of brain 4  Peripheral Nervous System can be further subdivided into: 1. Sensory Subdivision (Afferent subdivision) Which gathers and transmits information from the peripheral receptors and sensory organs to the CNS. 2. Motor Subdivision (Efferent subdivision) Which transmits information from the CNS out to the peripheral tissues (muscles, adipose, and glands) to cause an EFFect or action (ex. a muscle contraction or a secretion). 5  The Efferent Subdivision of the Peripheral Nervous System (PNS) has 2 further subdivisions: 1. Somatic Motor Subdivision: Controls skeletal muscles The output of this subdivision is under conscious control so it is said to be voluntary. 2. Visceral Motor Subdivision (a.k.a. Autonomic Nervous System (ANS): Regulates activity of involuntary muscles of the body as well as secretion of some glands (ex. salivary glands) and some endocrine glands, and adipose tissues. This subdivision is not under conscious control and so is said to be involuntary. 6  Autonomic Nervous System (ANS) The ANS is further divided into: Sympathetic Subdivision Parasympathetic Subdivision These two subdivisions work antagonistically to regulate body functions. The balance between the output of these two subdivisions of the ANS plays a major role in regulating the physiology of the organs and organ systems of the body. More on this later. 7  All neural tissue is composed of two types of cells: 1. Neurons: Functional units of the nervous system. Generate and conduct electrical signals to convey information. 2. Glial Cells: Serve a variety of support functions for the neurons including: Provide structural framework for the neurons. Regulate nutrients that enter/leave the CNS by forming a “blood-brain barrier”. Form scar tissues in the event the nervous system is damaged. 8 Glial Cells of the Central Nervous System. may also be 9 Glial Cells of the Peripheral Nervous System.  Neurons Specialized for transferring info from one part of the nervous system to another. For most of the nervous system this transfer of info is achieved by the translation of a chemical signal into an electrical signal, and then translation of the electrical signal back into chemical signal. 11  1. Dendrites 2. Chemical signal is translated into an electrical signal called a Post- Synaptic Potential (PSP) a.k.a ”soma” 3. If the PSP is of great enough amplitude, the axon hillock converts it into another electrical signal, AXON called an Action Potential (AP) 4. Upon entering the axon terminal, the AP triggers the release of neurotransmitter from the axon terminal onto the target cell (in this example another neuron). 12  SYNAPSES Electrical Synapses: APvery rare Gap Junctions Axon Axon Terminal Presynaptic membrane Synaptic Cleft TARGET CELL Postsynaptic membrane - Electrical synapses allow the AP to pass from axon terminal through gap junctions into the target cell. No neurotransmitters are released at electrical synapses. 13  SYNAPSES Chemical Synapses: most common type of synapse Chemical synapses use neurotransmitters (NT) to transmit signal: 1. AP triggers fusion of synaptic vesicles stored in the axon terminal with the pre-synaptic membrane 2. Results in release of NT into the synaptic cleft 3. NT diffuses across synaptic cleft and binds to receptors Presynaptic expressed on post-synaptic membrane membrane Target Cell Initiates a PSP in target cell 14 Membrane Potential (Voltage) across the cell membrane of Neurons Neurons have an electrical potential (voltage) across their cell membrane such that the inside of the neuron is negative relative to the outside. This is called the neuron’s membrane potential (“Vm”). Neuron - + 15  The membrane potential is primarily the result of a combination of 3 factors: 1. There is a uneven distribution of ions between the inside and outside of the neuron. The ions principally involved in creating the membrane potential are: Na+ K+ Negatively charged anion (A -) 16 Relative ion distributions contributing to creating the membrane potential [K+] [K+] Neuron [Na+] [Na+] [A-] [A-] 17 2. The cell membrane is 40x more permeable to K+ than it is to Na+. It is impermeable to A-. The cell membrane has K+ leak channels that allow K+ to cross the membrane. [K+] low K+ leak channel [K+] high Neuron [Na+] low [Na+] high [A-] very low + [A-] high 18  The Movement of K+ ions out will continue until the concentration gradient driving K+ out is balanced by electrical forces created by negative charge inside the neuron. At the balance point the negative charge inside the neuron pulls K+ ions back in through the leak channels. The membrane potential value where these two forces are balanced is called the equilibrium potential for K+: (EK+). [K+] E K+ = -90mV K+ leak channel [K+] [Na+] [Na+] [A-] + [A-] 19  The cell membrane is also slightly permeable to Na+. Na+ leaks inward across the cell membrane (there are no Na+ leak channels) due to the electrochemical gradient pulling on the Na+ ions. - So the overall cell resting membrane potential becomes more positive than -90mV 3. The Na+/K+ ATPase pump uses energy from hydrolysis of ATP to move 3Na+ out of the cell for every 2K+ it moves in. [K+] Na+/K+ ATPase pump [K+] [Na+] 2 [K+] [Na+] 3 [Na+] + [A-] [A-] 20  The combination of these factors results in an overall membrane potential (“Vm”) for most neurons of -70mV. SO: The overall membrane potential (Vm) across the membrane of a neuron is determined by the combination of: The uneven distribution of ions (primarily K+, Na+, and A-) across the cell membrane. The cell membrane’s relatively high permeability to K+, low permeability to Na+, and impermeability to A-. The Na+/K+ ATPase Pump moving more + charge out than it moves in which contributes a small amount to the final Vm. This membrane potential is stable at -70mV unless something changes (ex. membrane permeability to an ion changes). So, it is called the “Resting Membrane Potential”. 21 Changing the cell membrane’s ion permeability changes the neurons membrane potential (Vm). In addition to K+ leak channels, neurons also have gated channels. K+ leak channels Gated Na+ [K+] channels Gated K+ channels Vm = -70mV [Na+] 22  Electrical Signals Generated by Neurons Neurons use transient changes in their membrane potential resulting from opening and closing gated ion channels to generate two types of electrical signals: Post-synaptic potentials (PSPs) (a.k.a. Graded potentials) Action Potentials (APs) 23  5 features of PSPs (a.k.a. Graded Potentials) 1. They are initiated in the dendrites or soma of neurons as a result of the binding of neurotransmitter to receptor at a synapse on the neuron’s cell membrane, causing opening of ion channels. 5 features of PSPs (Graded Potentials) 2. They can be either depolarizing or hyperpolarizing, depending on the channels that open in response to the binding of neurotransmitter (NT) to receptor. A depolarizing PSP is called an Excitatory Post- synaptic Potential (EPSP). A hyperpolarizing PSP is called an Inhibitory post- synaptic potential (IPSP).  5 features of PSPs (Graded Potentials) 3. The amplitude of the depolarization or hyperpolarization that occurs following the binding of NT to receptor on the post-synaptic membrane depends on the amount of NT released from the axon terminal and subsequently the number of ion channels that open on the target cell membrane… The more neurotransmitter released onto the post-synaptic membrane More receptors are bound and activated More Ion channels that open More ion that move across the post-synaptic membrane The greater the amplitude of the depolarization or hyperpolarization (i.e. the more Vm is changed) 5 features of PSPs Graded Potentials 4. Graded potentials rely on passive flow of current to spread through the cytosol of the neuron Gated Na+ channel Na+ 1. Neurotransmitter (NT) binds to receptor ECF 2. Gated Na+ channel opens NT 3. Na+ flows in down electrochemical Cell membrane gradient Cytosol 4. Na+ repels other + charged ions in the cytosol Na+ 5. Wave of + charge spreads from the + site (“local current flow”) + + + + + + + + +  The cytosol has resistance to current flow, so as the wave of + charge spreads through the cytosol, it gets smaller. The distance the current flows depends on the amount of Na+ that crosses the membrane: - the more Na+ that crosses the membrane, - the greater the amplitude of the current flow, Current leak - and so the further the current will spread before it dissipates due to resistance in the cytosol and some current leak outward across the membrane.  EPSP EPSP EPSP EPSP * The Axon hillock (trigger zone) has an abundance of Na+ channels and voltage-gated K+ channels in its cell membrane. If the membrane potential of the axon hillock is depolarized enough to reach threshold (T), then these channels open and an AP is initiated (panel b).  5 features of PSPs (Graded Potentials) 5. Graded potentials sum together in two ways: Spatial Summation: Temporal Summation: Illustration of Spatial Summation Illustration of Temporal Summation Action Potentials Have 4 Characteristic Features: 1. They are initated at the axon hillock (a.k.a. trigger zone) of the axon. 2. They are “all or none” i.e. once initiated they go to completion and do not vary in amplitude. Vm at the axon hillock must reach threshold or no AP will be initiated! 3. They involve a depolarization of the membrane potential, followed by repolarization, then a hyperpolarization, before returning to the resting membrane potential. 4. They don’t diminish in amplitude as they move down the axon away from the trigger zone. (They’re actively conducted along the axon to the axon terminal).  Electrical Signals: Action Potential The action potential can be divided into three phases based on the changes in membrane potential: The Rising Phase The Falling Phase The Afterhyperpolarization Phase 35 Electrical Signals: Action Potential From Figure 8-9 (1 of 9) Electrical Signals: Action Potential (EPSP enters axon hillock) Electrical Signals: Action Potential Electrical Signals: Action Potential Rising phase Electrical Signals: Action Potential Vm has depolarized to +30mV during the time the voltage gated Na+ channels are open. Electrical Signals: Action Potential Falling phase Electrical Signals: Action Potential after-hyperpolarization phase  Electrical Signals: Action Potential After being open for 2-3msec, the voltage gated K+ channels begin to close, and the membrane’s permeability to K+ returns to normal.  Electrical Signals: Action Potential As the membrane’s ion permeability returns to normal, the membrane potential returns to the resting membrane potential (9) with the help of the Na+/K+ ATPase pump. Electrical Signals: Action Potential Questions?  Electrical Signals: Voltage-Gated Na+ Channels Voltage gated Na+ channels have two gates: an activation gate (closed at -70mV) inactivation gate (open at -70mV). Closed at -70mV Open at -70mV  Electrical Signals: Voltage-Gated Na+ Channels If a EPSP large enough to reach threshold depolarizes the membrane potential at the channel, the activation gate will open. Na+ ions will flow in through the open channel further depolarizing the membrane potential beyond threshold.  Electrical Signals: Voltage-Gated Na+ Channels After 1/2-3/4 msec, the inactivation gate will move in and close the channel. The inactivation gate channel closure lasts for about 1 msec. The inactivation gate will not open again during this 1 msec period.  Electrical Signals: Voltage-Gated Na+ Channels After 1msec, the gates reset and the channel can again open in response to a suprathreshold EPSP.  Refractory Period The axonal membrane has a refractory period defined as: The period of time following the initiation of an action potential during which it is difficult or impossible to initiate a second AP. The Refractory Period is the result of the Voltage-Gated Na+ Channels having Two Gates: The refractory period has two parts: 1) Absolute Refractory Period (ARP): The period of time during which a second AP cannot be initiated because the voltage-gated Na+ channels are already open, or they are closed by their inactivation gates and so cannot be re- opened. 2) Relative Refractory Period (RRP): Period of time during which a second AP can be initiated because gates voltage- gated Na+ channels of the have reset, but a larger than normal EPSP is required to reach threshold because the membrane is still hyperpolarized in the after- hyperpolarization phase of the AP.  Electrical Signals: Refractory Period Another AP cannot initiated during the absolute refractory period because the voltage gated Na+ channels already have their activation gates open, or later in the ARP, the channels are closed by their inactivation gates. During the relative refractory period the voltage gated Na+ channel gates have reset, so they can respond to an EPSP, but a larger amplitude EPSP is needed to reach threshold because the membrane is hyperpolarized.  Conduction of the Action Potential Once an AP is initiated at the axon hillock (i.e. trigger zone, it is actively conducted down the axon to the axon terminal. Conduction of the Action Potential 54 Conduction of the Action Potential 55  AP Conduction Velocity Speed of action potential conduction along the axon is influenced by two factors: 1. Diameter of axon. 2. Resistance of axon membrane to ion leakage out across the axonal membrane. Humans need fast transmission! Large diameter axons all over the body aren’t practical. Therefore, we rely on the myelination of axons for fast conduction.  Myelination increases the speed of AP conduction Has lots of voltage- gated Na+ and voltage gated K+ channels in its cell membrane. Myelination of the axon minimizes the leakage of + current out as the current moves down the axon. So the amplitude of the current flow is maintained above threshold when it reaches the next node of Ranvier. Recall: PNS Myelin is formed by Schwann cells. CNS myelin is formed by Oligodendrocytes.  Myelination increases the speed of AP conduction AP occurring here Current flow to next node In addition to minimizing current leakage outward across the membrane, myelin also reduces the number of channels that need to be opened during the conduction of the AP from the axon hillock to the axon terminal, thus action potential conduction is faster. The conduction speed limiting step in AP conduction is the opening of the voltage gated Na+ channels. if there are fewer channels that have to be opened to during conduction of the AP, the AP conduction velocity will be faster. So, in a myelinated axon only the voltage gated Na+ channels at the nodes of Ranvier have to be opened and the action potential appears to “jump” from node of Ranvier to node of Ranvier down the length of the axon. This is called “Saltatory Conduction”.  Cell-to-Cell Communication: Chemical Synapse Electrical synapses pass electrical signals to target cells through gap junctions. At chemical synapses a neurotransmitter is used to signal the target cell. Structure of a chemical synapse  How Does Neurotransmitter Release Occur at a Chemical Synapse? Action 1 An action potential depolarizes potential the axon terminal. Axon terminal Synaptic vesicle 1 Pre-synaptic membrane Post-synaptic AKA: “Target membrane Postsynaptic cell” cell How Does Neurotransmitter Release Occur at a Chemical Synapse? Action 1 An action potential depolarizes potential the axon terminal. 2 The depolarization opens voltage- gated Ca2+ channels and Ca2+ enters the cell. Axon terminal Synaptic vesicle Ca2+ is in high concentration in the ECF and is in low 1 concentration inside Ca2+ the neuron. Voltage-gated Ca2+ Ca2+ channel 2 Postsynaptic cell How Does Neurotransmitter Release Occur at a Chemical Synapse? Action 1 An action potential depolarizes potential the axon terminal. 2 The depolarization opens voltage- gated Ca2+ channels and Ca2+ enters the cell. Axon terminal Synaptic 3 Calcium entry triggers exocytosis vesicle of synaptic vesicle contents. Ca2+ triggers the binding 1 of the synaptic vesicles Ca2+ 3 to docking proteins in the pre-synaptic membrane. This Voltage-gated opens a pore in the presynaptic Ca2+ Docking Ca2+ channel 2 membrane, and the NT diffuses out protein into the synaptic cleft. Postsynaptic cell How Does Neurotransmitter Release Occur at a Chemical Synapse? Action 1 An action potential depolarizes potential the axon terminal. 2 The depolarization opens voltage- gated Ca2+ channels and Ca2+ enters the cell. Axon terminal Synaptic 3 Calcium entry triggers exocytosis vesicle of synaptic vesicle contents. 4 Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell. 1 Ca2+ 3 Voltage-gated Ca2+ Docking Ca2+ channel 2 protein 4 NT binds to receptor. Receptor Postsynaptic AKA: “Target cell cell” How Does Neurotransmitter Release Occur at a Chemical Synapse? Action 1 An action potential depolarizes potential the axon terminal. 2 The depolarization opens voltage- gated Ca2+ channels and Ca2+ enters the cell. Axon terminal Synaptic 3 Calcium entry triggers exocytosis vesicle of synaptic vesicle contents. 4 Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell. 1 Ca2+ 3 5 Neurotransmitter binding initiates a response in the postsynaptic cell. Voltage-gated Ca2+ Ca2+ channel 2 Docking protein 4 When the receptor binds Receptor NT it initiates a response Postsynaptic 5 cell in the target cell. The Cell response response will depend on the receptor, not the NT. Two Types of Responses Can Occur in the Post-synaptic Cell Following Binding of NT: 1. A graded potential (i.e. an IPSP or EPSP). This is called a “fast synaptic response” because it happens quickly and lasts only a few msec. Two Types of Responses Can Occur in the Post-synaptic Cell Following Binding of NT: 2. Slow Synaptic Responses: The receptor is linked to a G- Protein on the inside of the post-synaptic cell (i.e. target cell) membrane. Binding of NT causes a second messenger system to phosphorylate proteins in the target cell. a) This results in opening or closing of ion channels in cell membranes of the target cell, thus changing the resting membrane potential of the target cell. OR b) This can cause a change in the metabolism of the target cell. **In either case, a slow synaptic response takes longer to occur and last longer than a fast synaptic response. Neurocrines are the chemical signal molecules synthesized by neurons Neurocrines Include: Neurohormones Are chemical signals synthesized by neurons and released into the blood for transport to target cells like a hormone.. Neurotransmitters Are chemical signal synthesized by neurons. Stored in and released from synaptic vesicles at a synapse in response to depolarization of the axon terminal. Cause a response in the target cell. Neuromodulators Are chemical signals synthesized by neurons. May or may not be stored in and released from synaptic vesicles. Alter the activity of other neurons in the vicinity or at a distance. Some neurocrines can fit into more than one of these definitions, i.e. depending on how the chemical signal is being used it may be described as a neurotransmitter, a neuromodulator, or a neurohormone. Ex. Epinephrine is used as a neurotransmitter by some neurons or as a neurohormone when it is secreted by the adrenal medulla into the blood. 5 types of neurocrines are used as by neurons as neurotransmitters: Acetylcholine: used as a neurotransmitter by somatic motor neurons and by preganglionic neurons of the ANS. Amines: include dopamine, norepinephrine & epinephrine are used as neurotransmitters by some of the neurons. Ex. Sympathetic postganglionic neurons use norepinephrine as their neurotransmitter.  Amino Acids: Glycine is used by some neurons in spinal cord as a neurotransmitter (evokes IPSPs in target cells). Glutamate is used by some neurons in the brain and spinal cord as a neurotransmitter (evokes EPSPs in target cells). Peptides: some neurons use peptides (“neuropeptides) as their neurotransmitter. Many neuropeptides may also be used as neurohormones or neuromodulators. Purines: some neurons use ATP as their neurotransmitter.  “Unconventional” Neurotransmitters Some neurocrines do not fit the definition for being considered neurotransmitters. But the book includes them under the section on neurotransmitters and some neuroscientists refer to them as “unconventional” neurotransmitters. Gases: Some neurons synthesize gases, like Nitric oxide, that diffuse out of the neuron and affect neighboring cells by diffusion, rather than binding receptors. Note: These gases are not stored in or released from synaptic vesicles. They are synthesized in response to stimulation and diffuse across the neuronal membrane into nearby neurons. Lipids: Some post-synaptic neurons synthesize and use small lipid molecules to modulate the activity of pre-synaptic neurons (ex. Endocannabinoids are released into synaptic cleft from post-synaptic cells and act on cannabinoid receptors expressed on the axon terminal to decrease the release of neurotransmitter at the synapse). These lipids are synthesized at the time of release, they are not stored in synaptic vesicles and are not released in response to depolarization of the axon terminal. They also act on the presynaptic neuron rather than the post-synaptic neuron. ***There is currently no consensus regarding whether these “unconventional” neurotransmitters should be considered to be neurotransmitters or neuromodulators.  Cell-to-Cell Communication: Inactivation of Neurotransmitters After stimulating the target cell the NT must be removed from the synaptic cleft to prevent over stimulation of the target cell. This removal occurs in several ways. Re-uptake transporter Cell-to-Cell: Inactivation of Neurotransmitters Cell-to-Cell: Inactivation of Neurotransmitters