Understanding Neurophysiology and Histology: Nervous System's Structure and Function - Pro, Study notes of Neurobiology

Download Understanding Neurophysiology and Histology: Nervous System's Structure and Function - Pro and more Study notes Neurobiology in PDF only on Docsity! Chapter 3 - A goal of cellular neurophysiology is to understand the biological mechanisms that underlie a nervous system to collect, distribute, and integrate information - Action potential: a brief fluctuation in membrane potential caused by the rapid opening and closing of voltage-gated ion channels; also known as spike, nerve impulse, or discharge; it sweeps like a wave along axons to transfer information from one place to another in the nervous system - Excitable membrane: any membrane capable of generation action potentials (axons and muscle cells) - Resting membrane potential: the membrane potential, or membrane voltage, maintained by a cell when it is not generating action potentials; also called resting potential. Neurons have a resting potential of about -65 mV - Water is the main ingredient of the cytosol (fluid inside the neuron) and the extracellular fluid - Ion : an electrically charged atom or molecule - Water has an uneven distribution of electrical charge. The electrons covalently bonded between the oxygen and hydrogen atoms tend to be more attracted to the oxygen therefore the oxygen atom acquires a negative charge, making the molecule polar. - Polar molecules dissolve well in water - Spheres of hydration: water molecules that surround ions when being dissolved - Monovalent : when the difference between the number of protons and electrons in an ion is 1 (Na+ K+, and Cl- are important for cellular neurophysiology) - Divalent : when the difference between the number of protons and electrons in an ion is 2 (Ca2+ is important for cellular neurophysiology) - Cations : a positively charged ion - Anion : a negatively charged ion - Hydrophilic : “water-loving;” ions and polar molecules that dissolve well in water - Hydrophobic : “water fearing;” molecules with non-polar covalent bonds that do not dissolve in water - Phospholipid bilayer: the arrangement of phospholipid molecules that forms the basic structure of the cell membrane. The core of the bilayer is lipid, creating a barrier to water and to water-soluble ions and molecules out of nonpolar chains of carbon atoms bonded to hydrogen atoms as well as a phosphate group (P atom bonded to three O atoms) known as the polar head - Protein: a molecule made from various combinations of 20 difference amino acids - Amino acids: have a central carbon, a hydrogen atom, an amino group (NH3+), and carboxyl group (COO-) and an R group - The properties of the R group determine the chemical relationships in which each amino acid can participate - Peptide bond: the covalent bond between the amino group of one amino acid and the carboxyl group of another - Polypeptide: a string of amino acids held together by peptide bonds - Protein structure:  primary chain: amino acids are linked together by peptide bonds in a chain  alpha helix: secondary structure where the primary chain coils into a spiral-like configuration  tertiary structure: created when R groups interact with one another and change its three-dimensional shape (bend, fold, create globular shape)  quaternary structure: when different polypeptide chains (subunits) bond and create a larger molecule - Ion channel: a membrane-spanning protein that forms a pore that allows the passage of ions from one side of the membrane to the other - Ion selectivity: a property of ion channels that are selectively permeable to some ions and not to others - Gating : a property of many ion channels, making them open or closed in response to specific signals, such as membrane voltage or the presence of neurotransmitters - Ion pump: a protein that transports ion across a membrane at the expense of metabolic energy - ionic movements through channels are influenced by two factors: diffusion and electricity - diffusion : the temperature-dependent movement of molecules from regions of high concentration to regions of low concentration, resulting in a more even distribution - the rate of diffusion is proportional to the temperature - concentration gradient : a difference in concentration from one region to another. Ionic concentration gradients across the neuronal membrane help determine the membrane potential - ions are driven across the membrane through diffusion when the membrane possesses channels permeable to the ions and there is a concentration gradient across the membrane - electrical current : the rate of movement of electrical charge, represented by the symbol I and measured in amperes (amp) - electrical potential (voltage) and electrical conductance determine how much current will flow - electrical potential/voltage : the force exerted on an electrically charged particle, represented by the symbol V and measured in volts; also called voltage or potential difference - more current will flow as the difference in charge between the anode and cathode increases - electrical conductance : the relative ability of an electrical charge to migrate from one point to another, represented by the symbol g and measured in siemens (S). it depends on the number of particles available to carry electrical charge and the ease with which these particles can travel through space - electrical resistance: the relative inability of an electrical charge to migrate from one point to another, represented by the symbol R and measured in ohms (W); the inverse of conductance - Ohm’s law: the relationship between electrical current (I), voltage (V), and conductance (g): I=gV. Because electrical conductance is the inverse of resistance (R), Ohm's law may also be written V=IR - ions are driven across the membrane electrically when the membrane possesses channels permeable to that ion and if there is an electrical potential difference across the membrane - membrane potential : the voltage across a cell membrane; represented by the symbol Vm - microelectrode : a probe used to measure the electrical activity of cells; has a very fine tip and can be fashioned from etched metal or glass pipettes filled with electrically conductive solutions - the inside of the neuron is electrically negative with respect to the outside - the resting potential of a typical neuron is -65mV (millivolts) - equilibrium potential: the electrical potential difference that exactly balances an ionic concentration gradient, represented by the symbol Eion; also known as equilibrium potential - Ex) The inside of a cell has a high and equal concentration of positively and negatively charged ions (K+ and A-). The outside of the cell has a lower but still equal concentration of the same positively charged ions. They are separated by a phospholipid bilayer and therefore there is no net movement of ions. If a potassium channel was inserted into the phospholipid bilayer, then the K+ ions would move from the inside to the outside of the cell, due to the concentration gradient. As the K+ ions leave the cell, they leave the A- ions inside the cell, making the inside of the cell negative. This attracts the K+ ions back through the potassium channel. Eventually an equilibrium state is reached when the diffusional and electrical forces are equal and opposite, and the net movement of the K+ ions is zero again. - large changes in membrane potential are caused by miniscule changes in ionic concentrations - the net difference in electrical charge occurs at the inside and outside surfaces of the membrane (the membrane is so thin that the anions on the inside and the cations on the outside tend to be mutually attracted to the cell membrane). This property of the membrane storing electrical charge is called capacitance - ions are driven across the membrane at a rate proportional to the difference between the membrane potential and the equilibrium potential - ionic driving force: the difference between the real membrane potential, Vm, and the ionic equilibrium potential, Eion - if the concentration difference across the membrane is known, an equilibrium potential can be calculated for that ion - [IS THIS CORRECT??] if the ion concentration is higher on the inside, that ion has a negative equilibrium potential if the membrane was selectively permeable to that ion - [IS THIS CORRECT??] if the ion concentration is higher on the outside, that ion has a positive equilibrium potential if the membrane was selectively permeable to that ion - each ion has its own equilibrium potential if the membrane were permeable only to that ion - Nernst equation: a mathematical relationship used to calculate an ionic equilibrium potential - sodium-potassium pump: an ion pump that removes intracellular Na+ and concentrates intracellular K+, using ATP for energy because it pushes the ions across their concentration gradients (up to 70% of the brain’s ATP) - calcium pump: an ion pump that removes cytosolic Ca2+ - Goldman equation : a mathematical relationship used to predict membrane potential from the concentrations and membrane permeabilities of ions the neuronal membrane at rest is mostly permeable to K+ so the membrane potential is close to EK. - depolarization : a change in membrane potential, taking it from the value at rest to a less negative value (ex. -65 mV to 0mV) - This means that increasing extracellular potassium depolarizes neurons - blood-brain barrier : a specialization of the walls of brain capillaries that limits the movement of blood-borne substances (like potassium) into the extracellular fluid of the brain - potassium spatial buffering : the mechanism of regulating K+ ions by astrocytes Chapter 2 - there are two types of cells in the nervous system: neurons and glia - in the brain, glia outnumber neurons (which are about 100 billion) tenfold - neurons are the most important cells for the unique functions of the brain - material is enclosed within vesicles that “walk down” the microtubules with “legs” made from kinesin - anterograde transport: axoplasmic transport from a neuron's soma to the axon terminal. The “legs” are made from kinesin - retrograde transport: axoplasmic transport from an axon terminal to the soma; usually occurs when providing signals regarding metabolic needs. The “legs” are provided by dyenein - dendritic tree: all the dendrites of a single neuron - dendrites are covered with thousands of synapses because they function as the antennae of the neuron - receptors : 1) a specialized protein that detects chemical signals, such as neurotransmitters, and initiates a cellular response 2) a specialized cell that detects environmental stimuli and generates neural responses - dendritic spine: a small sac of membrane that protrudes from the dendrites of some cells and receives synaptic input. They are believed to isolate various chemical reactions that are triggered by some types of synaptic activation - Spine structure is sensitive to the type and amount of synaptic activity. Unusual spine structure is linked with cognitive impairments - Dendrite structure is very similar to axon structure. The major difference is that polyribosomes have been found in dendrites, often right underneath the spines - Neurons can be classified by the total number of neurites (axons and dendrites) that extend from the soma - unipolar neuron: a neuron with a single neurite - bipolar neuron: a neuron with two neurites - multipolar neuron : a neuron with three or more neurites (most fall into this category) - in the cerebral cortex there are two broad classes of neurons: stellate cells and pyrmidal cells - stellate cell: a neuron characterized by a radial, star-like distribution of dendrites - pyramidal cell: a neuron characterized by a pyramid-shaped cell body and elongated dendritic tree; found in the cerebral cortex - spiny neuron: a neuron with dendritic spines - aspinous neuron: a neuron lacking dendritic spines - primary sensory neuron: a neuron specialized to detect environmental signals at the body's sensory surfaces - motor neuron: a neuron that synapses on a muscle cell and causes muscle contraction - interneuron : any neuron that is not a sensory or motor neuron; also describes a CNS neuron whose axon doesn't leave the structure in which it resides; it forms connections between other neurons; this is the most common neuron in the nervous system - Golgi type I neurons (projection neurons) : neurons with axons that extend from one part of the brain to the other (pyramidal cells in the cerebral cortex) - Golgi type II neurons (local circuit neurons) : neurons with axons that don’t extend past the soma (stellate cells in the cerebral cortex) - cholinergic : term used to describe neurons that can be classified by their use of a particular neurotransmitter - astrocyte : a glial cell in the brain that supports neurons and regulates the extracellular ionic and chemical environment; the most numerous glial cell in the brain a) envelop synaptic junctions thereby restricting the spread of neurotransmitters b) have proteins in their membranes that actively remove many neurotransmitters from the synaptic cleft c) have membranes that possess neurotransmitter receptors that can trigger electrical and biochemical events inside the glial cell d) control the extracellular concentration of several substances such as K+ ions - astrocytes probably influence whether a neuron can grow or retract - oligodendroglial cell: a glial cell that provides myelin in the central nervous system; can contribute myelin to several axons - Schwann cell: a glial cell that provides myelin in the peripheral nervous system; myelinates only a single axon - myelin : a membranous sheath around axons provided by oligodendroglia in the central nervous system and Schwann cells in the peripheral nervous system - node of Ranvier: a space between two consecutive myelin sheaths where an axon comes in contact with the extracellular fluid - ependymal cell: a type of glial cell that provides the lining of the brain’s ventricular system - microglial cell: a type of cell that functions as a phagocyte in the nervous system to remove debris left by dead or dying neurons and glia Chapter 4 - rising phase: the first part of an action potential, characterized by a rapid depolarization of the membrane - overshoot : the part of an action potential when the when the membrane potential is more positive than 0 mV - falling phase: the part of an action potential characterized by a rapid fall of membrane potential from positive to negative - undershoot: the part of an action potential when the membrane potential is more negative than at rest; also called after- hyperpolarization - after-hyperpolarization: the hyperpolarization that follows strong depolarization of the membrane; the last part of an action potential, also called undershoot - the action potential lasts about 2 milliseconds (msec) - threshold : a level of depolarization sufficient to trigger an action potential - absolute refractory period: the period of time, measured from the onset of an action potential, during which another action potential cannot be triggered - relative refractory period: the period of time following an action potential during which more depolarization current than usual is required to achieve threshold - depolarization of the cell during the action potential is caused by the influx of Na+ ions across the membrane, and repolarization is caused by the efflux of K+ ions - the number of open potassium channels is proportional to an electrical conductance (gK) - IK will flow as long as Vm  EK; the current flow is in the direction that takes Vm toward EK. When Vm = EK, the membrane is at equilibrium and no net current will flow even though there is still a large potassium conductance - The rising phase of the action potential could be explained if, in response to depolarization of the membrane beyond threshold, membrane sodium channels opened, allowing Na+ to enter the neuron, causing a massive depolarization until the membrane potential approached ENa. The sodium current Ina is inward across the membrane in this case [ (Vm - ENa)  ( -80mV - 62mV = -142mV ) ] - The influx of Na+ depolarizes the neuron until Vm approaches ENa, assuming the membrane permeability is now far greater to sodium than it is to potassium - Sodium channels quickly close and the potassium channels remain open, so the dominant membrane ion permeability switches back from Na+ to K+ (then K+ would flow out of the cell until the membrane potential again equals EK - The rising phase of the action potential is explained by an inward sodium current and the falling phase is explained by an outward potassium current - voltage clamp: a device that enables an investigator to hold the membrane potential constant while transmembrane currents are measured - the rising phase of the action potential was caused by a transient increase in gNa and an influx of Na+ ions; the falling phase was associated with an increase in gK and an efflux of K+ ions - voltage-gated sodium channel: a membrane protein forming a pore that is permeable to Na+ ions and gated by depolarization of the membrane - the VG sodium channel is made from a single long polypeptide with four distinct domains (each made of six transmembrane alpha helices) - the four domains form a pore between them; the pore is closed at the negative resting membrane potential; when the molecule is depolarized to threshold, the molecule twists and allows Na+ to flow through - patch clamp: a method that enables an investigator to hold constant the membrane potential of a patch of membrane while current through a small number of membrane channels is measured - properties of voltage-gated sodium channels: a) they open quickly b) they stay open for 1msec then inactivate c) they cant be opened by depolarization again until the Vm returns to a negative value near threshold (accounts for the absolute refractory period) - channelopathy: a human genetic disease caused by alterations in the structure and function of ion channels - generalized epilepsy with febrile seizures: a channelopathy with epileptic seizures caused by high fevers. This is linked to mutations that slowed the inactivation of the VG sodium channels, prolonging the action potential - tetrodotoxin (TTX): a toxin that binds to the outside of the Na+ channel and clogs the Na+ permeable pore; (found in puffer fish) - saxitoxin : another channel blocking toxin found in dinoflagellates, which when bloom create the “red tide” - batrachotoxin (found in poison dart frogs), veratridine (lillies), and aconitine (buttercups): causes the channels to open at more negative potentials and stay open much longer - delayed rectifier: when channels take about 1msec to open upon depolarization (rather than immediately); ex. potassium gates - voltage-gated potassium channel: a membrane protein forming a pore that is permeable to K+ ions and gated by depolarization of the membrane - the VG potassium channel is made from four individual polypeptide with four distinct domains - when the membrane is depolarized, the voltage sensors detect a change in electrical field and twist the subunits into a shape that allows the K+ ions to pass through - ACTION POTENTIAL OVERVIEW: a) threshold: Vm at which VG Na+ channels open and allow the ionic permeability favor Na+ instead of K+ b) rising phase: inside of membrane has a neg. electrical potential and creates a large gN. Na+ ions rush into the cell through open VG Na+ channels and cause the membrane to rapidly depolarize c) overshoot: the membrane permeability favors Na+ and goes towards its ENa, which is greater than 0mV d) falling phase: VG Na+ channels inactivate. VG K+ channels finally open (triggered to do so 1msec after depolarization  delayed rectifier). K+ ions rush out of the cell causing the membrane potential to become negative again e) undershoot: there is very little Na+ permeability so the Vm goes towards EK causing a hyperpolarization (relative to the resting Vm) until the VG K+ channels close again f) absolute refractory period: the Na+ channels inactivate after the Vm becomes strongly depolarized and cannot be activated again until the Vm goes sufficiently negative to deinactivate the channels g) relative refractory period: the Vm stays hyperpolarized until the VG K+ channels close, requiring a greater depolarizing current in order to bring the Vm back to threshold - The action potential, from start to finish, usually lasts 2msec - Once generated, the action potential must be conducted down the axon (similar to burning a fuse) - Axon is depolarized to reach threshold  VG Na+ channels open  action potential is initiated  influx of positive charge depolarized the membrane segment immediately before it until it reaches threshold  that segment generates its own action potential  continues down the axon until it reaches the axon terminal  initiates synaptic transmission - Action potential can be generated at either end of the axon but can only propagate in one direction because the membrane behind it is refractory (due to the inactivation of the Na+ channels) - Orthodromic conduction: action potential going in one direction - Antidromic conduction : propagation from axon terminal to dendrites (sometimes elicited experimentally) - Typically action potential velocity is around 10m/sec - The farther the current goes down the axon, the farther ahead of the action potential the membrane will be depolarized, and the faster the action potential will propagate - Axonal size and the number of VG channels in the membrane affect axonal excitability - Action potential conduction velocity is proportional to axonal diameter - Smaller axons require greater depolarization to reach action potential threshold and are more sensitive to being blocked by local anesthetics - Fat axons conduct action potentials faster but take up a lot of space  vertebrates evolved myelin - Myelin sheath : many membrane layers (either of glial or oligodendroglial cells) that wrapped around the axons that facilitate current flow thereby increasing action potential conduction velocity. - VG Na+ channels are concentrated in the membrane of the nodes of Ranvier - saltatory conduction: the propagation of an action potential down a myelinated axon - spike-initiation zone: another name for the axon hillock; a region of the neuronal membrane where action potentials are normally initiated, characterized by a high density of voltage-gated sodium channels