Neurophysiology, Sensory and Motor systems Notes PDF

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Neurophysiology, Sensory and Motor SystemsThe Neuronal Membrane at RestSimple Reflex 1. Sense the puncture via the sensory neuron 2. In spinal cord, information is relayed through intermediary neuron 3. Intermediary neuron is split up and distributedTime frame for distribution of two signals to moto...

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Neurophysiology, Sensory and Motor Systems

The Neuronal Membrane at Rest Simple Reflex 1. Sense the puncture via the sensory neuron 2. In spinal cord, information is relayed through intermediary neuron 3. Intermediary neuron is split up and distributed Time frame for distribution of two signals to motor system and higher motor cortex systems is different 1. Protects body (unconscious movement) = reflex arc Action Potential 2. Neurons conduct info over distance using electrical signals 3. Axonal membrane conducts action potential 4. Do not diminish with distance- constant amplitude o Information is encoded through action potential frequency instead of amplitude 5. Cells capable of conducting and generating APs are excitable membranes Resting membrane potential (RMP) Resting: not receiving or generating signals 6. Cytosol (Inside surface) has negative charge compared to positive outside 7. Difference in electrical charge determines RMP 8. AP is brief reversal of the condition Cytosol and extracellular fluid Water +

Ions

Main constituent of fluid inside and outside the neuron

Atoms or molecules with net electric charge

Uneven distribution of electrical charge - has a dipole moment

Electrical charge depends on difference between protons and electron 9. Monovalent and divalent ions

Polar molecule held together by polar covalent bonds

Ions with net positive charge are cations

Good polar solvent of other charged or polar molecules

Ions with net negative charge are anions In water, ions are surrounded by a hydration shell Major charge carriers involved in conduction of electricity in biological systems Important ions are Na+, K+, Cl-, Ca2+

Phospholipid membrane 10. Membrane isolates cytosol of the neuron from the extracellular fluid o Phospholipids are main building blocks of membranes

Hydrophilic polar head (phosphate) and hydrophobic non-polar tail (hydrocarbon) Neuronal membrane consists of a sheet of phospholipids (two molecules thick) 

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Proteins 1. Integral membrane proteins 2. Membrane-associated proteins 3. Cytosolic proteins 4. Transport proteins o Ion channels:  Formed by 4-6 similar protein subunits or domains surrounding a pore  Passive ion flow across the membrane  Along electrochemical gradient  Ion selectivity  Gating o Exchangers:  Move ions across membrane against electrochemical gradient  Fueled by transport of other ions or solutes along their gradients o Pumps:  Move ions across membrane against their electrochemical gradient  Using energy released by breakdown of ATP Diffusion Ionic movement through ion channels are influenced by diffusion and electricity . Ions and molecules dissolved in water are in constant motion . Temperature dependent, random movement distributed ions evenly throughout the solvent . Net movement of ions from regions of high to low concentration . Difference in concentration is concentration gradient . Ions flow down the concentration gradient Ions are driven across membrane by diffusion when… 1. The membrane possesses channels permeable to ions 2. There is a concentration gradient Electricity Electricity can induce net movement of ions in a solution

Net movement of Na+ towards negative side (cathode) and Cl- will go to positive side (anode) due to the attraction of charges NaCl is dissolved in equal concentrations on each side of the phospholipid bilayers . Large potential difference across the membrane generated by wires connected to battery terminals

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No current flows because there are no channels to allow the movement of Na+ and Cl- across the membrane o Conductance of the membrane is 0

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Current flows because there are open channels permeable to Na+ and ClAllows them to cross the membrane Electrical potential difference across the membrane

Ohms Law Electrical current (I): movement of charge in Ampere (A) Factors affecting how much current flows 1. Electrical potential o AKA voltage o Force exerted on a charged particle o Reflects the difference in charge between the anode and the cathode o More current will flow as this difference is increase o Volts (V) 2. Electrical conductance (g) o Relative ability of an electrical charge to migrate from one point to another o Siemens (S) Electrical Resistance (R): reciprocal of conductance (1/g) or the relative inability of an electrical charge to migrate in Ohms (Ω) Ohms Law:

I =gv

or I=

V R

Relationship between potential (V), conductance (g) or resistance (R) and the amount of current (I) that will flow Current = voltage ÷ resistance Membrane Potential Vm . Difference in electrical charge (at RMP, inside of cell is at -70mV) Conditions 1. Electrically charged ions in solution on either side of neuronal membrane 2. Ions cross the membrane only through protein channels when they are open 3. Protein channels highly selective for specific ions 4. Movement of any ion through channel depends on concentration gradient and difference in electrical potential across the membrane . .

Voltage across the membrane at any given moment Measured by inserting microelectrode into cytosol o Thin glass tube with fine tip that penetrates the membrane o Filled with electrically conductive salt solution and connected to voltmeter o Voltmeter measures electrical potential difference between the salt tip of microelectrode and reference electrode placed outside the cell

Ionic equilibrium potential Eion: Electrical potential difference that balances ionic concentration gradient Generating steady electrical potential difference requires 1. Ionic concentration gradient 2. Selective ion permeability Large changed in Vm (membrane potential) caused by miniscule changes in ionic concentrations (large Vm = small ionic conc) 2. Net difference in electrical charge occurs inside and outside of the membrane 3. Ions are driven across the membrane at rate proportional to difference between Vm. (membrane potential) and Eion (ionic equilibrium potential) o Difference between real Vm and Eion is the ionic driving force 2. If concentration difference is known, an equilibrium potential can be calculated for that ion 1.

Nernst Equation Each ion has its own equilibrium potential . steady electrical potential achieved if membrane permeable to only 1 ion Exact value of Eion in mV can be calculated using Nernst equation

Ionic equilibrium potential = 8.314 * Temp Faradays constant * valence of the ion.

ln outside conc of ion Inside conc of ion

Important features . Applies to only one type of ion whose concentrations are used . Equilibrium potential is independent of Vm and membrane permeability for the given ion . Value of equilibrium potential relative to Vm determine direction the ion will flow through open ion channels o Ion flow determines response of a neuron to synaptic input Distribution of ions across a membrane Resting membrane potential depends on distribution of ions across the membrane and selective membrane permeability for every given ion Distribution of ions across the membrane is unequal . Intracellular anions that cannot cross the membrane electrically are counterbalanced by high concentrations of intracellular + . Intracellular compartment is electrically neutral . Na+ has a higher concentration outside the cell So, at RMP of -60mV, K+ and Na+ are not at equilibrium

Relative ion permeabilities of the membrane at rest . Equilibrium potential for an ion is the Vm that results If the membrane is selectively permeable to ion alone o Neuronal membranes ARE NOT permeable to only one single type of ion

Permeable to only K+ = Vm = Ek (-80mV) Permeable to only Na+ = Vm. = Ena (+62 mV) Equally permeable to K+ and Na+ = Vm average of Ek and Ena 40x more permeable to K+ than to Na+ = Vm between Ek and Ena but closer to Ek

Na+/K+ ATPAse action . Maintains the RMP . . . . . .

Small amount of Na+ entering and passive efflux of K+ would dissipate conc gradients of the two ions across the membrane Action of Na+/K+ pump which transports Na+ out of the cell maintains concentration gradient Passive efflux of K+ compensated for by active influx of K+ 2K+ in and 3Na+ out Fueled by ATP Slightly electrogenic

Goldman-Hodgkin-Katz equation Determines the resting potential of a neuron . Concentration difference and membrane permeability of each that crosses the membrane must be taken into account

Pk, Pna, Pcl are permeabilities of K+, Na+, and Cl- respectively Em is membrane potential R, T, and F are same constants used in Nernst equation A regulation of external potassium concentration

RMP is close to Ek because the neuronal membrane at rest is mostly permeable to K+ . Vm is also sensitive to changes in concentration of extracellular potassium An increase in K+ will increase the Vm causing depolarization (negative to positive) of the membrane potential . Increasing cellular potassium depolarizes neurons Extracellular K+ is tightly regulated by the brain

The Action Potential Electrical signal currency in neurons  info conducted using electrical signals along axons  Axonal membrane conducts an action potential  Cytosol of neurons at rest is -ve  Action potential is rapid, short-lived reversal of this situation  APs do not diminish over distance = fixed size and duration  Information encoded as AP frequency (input encoded as an amplitude)

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Resting Phase a. Na+ outside the cell, K+ outside the cell b. -70mV Rising Phase a. Rapid depolarization (negative to positive internal charge caused by influx of Na+ ions into the neuron through the permeable Na+ channels down the conc gradient) of the membrane = continues until Vm reaches +40 mV b. generator potential c. has a graded, local effect until it crosses the threshold Overshoot a. Part of the AP where the inside of the neuron is positively charged with respect to the outside Falling phase a. Rapid repolarization (positive to negative charge caused by opening of K+ channels causing passive efflux of K+ to the outside of the cell, restoring the negative charge inside) until membrane is more negative than the RMP (-70mV) Afterhyperpolarization/undershoot a. Last part of the falling phase where Vm is more negative than the RMP

Initiation of action potential  If the generator potential achieves a critical level, the membrane generates an action potential  Depolarization through injecting electrical current through microelectrode a. If continuous depolarizing current is injected, neuron generates many APs in succession

Rate of AP generation depends on the magnitude of the injected

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current o

Firing frequency of APs reflects the magnitude of the depolarizing current (↑depolarizing current = ↑ frequency of AP) a. Way that stimulation intensity is encoded in the nervous system

Rapid generation of Aps o Maximum frequency of 1000 Hz a. Following every action potential is a refractory period where it is more difficult to excite a neuron to generate another action potential Refractory Period 1. ionic distribution reversed after depolarization and repolarization 2. RMP restored via sodium potassium pump Absolute refractory period 1 ms Occurs while the membrane is repolarizing and immediately

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afterwards No new action potential can be generated because the threshold I

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infinite Relative refractory period Several ms Threshold is higher than normal New action potential can be generated if the stimulus is sufficiently

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strong How is AP generated

Ik

Net movement of K+ across the membrane is an electrical current

gk

Number of open potassium channels is proportional the electrical conductance of the membrane to K+

Vm-Ek is the driving force

Ik (K+) will flow only as long as Vm (membrane potential) doesn’t equal to Ek (potassium equilibrium potential)

Ohms law Relationship between ionic driving force, ionic Ik = gk (Vm - Ek) conductance and the amount of ionic current that will Iion = gion (Vm flow Eion) Na+ channel Voltage gated sodium channels form a highly selective pore that opens and closes due to changes in the electrical potential of the membrane o Do not have thresholds o Na+ channel opens due to depolarization (negative to positive membrane potential through influx of Na+) o Open with little delay o Stay open for a short period of time then inactivate a. explains why AP is brief b. accounts for absolute refractory period o Cannot be opened again until they close (at negative membrane potentials) o Molecular model for inactivation of sodium channels is the hingeand-lid model Tetrodoxin Isolated from the ovaries of pufferfish Blocks Na+ channels a. clogging the pore upon tight binding to a site on the outside of the channel Blocks all Na+ dependent APs

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K+ channels o o

Falling phase of AP due to inactivation of Na+ channels and increase in gk that speed up the restoration of the -Vm after the AP K+ gates open with a delay

Summary of Action potential Threshold

Specific value of Vm where the net ionic current changes from outward to inward, depositing positive charge on the inside of the membrane

Rising phase

At -Vm, driving force for Na+ is very high so Na+ ions rush into the cell through open Na+ channels causing the membrane to rapidly depolarize

Overshoot

Due to high permeability to Na+, Vm approaches a value close to Ena which is greater than 0 mV

Falling phase

Du to inactivation of Na+ channels and the opening of voltage gated K+ channels. At depolarized Vm, driving force for K+ is high, so K+ ions rush out of the cell causing Vm to become negative

Afterhyperpolariz ation

Both voltage-gated and non-gated K+ channels open. Vm approached Ek, which is more negative than the RMP

Absolute refractory period

After opening due to depolarization, Na+ channels inactivate. AP not generated again until Vm goes negative to deinactivate the channels

Relative refractory period

Vm is more negative than the RMP because of the elevated permeability to K+ causing more depolarizing current required to reach the threshold

AP conduction o Na+ channels open when axon is depolarized to reach threshold, initiating an AP o Influx of positive charge depolarizes the segment of membrane downstream until it reaches threshold and generates its own AP o AP goes down the axon until it reaches the axon terminal where it initiates synaptic transmission o Excitable axonal membrane along the length causes AP will propagate without decrement o Axons conduct APs in both directions but does not turn around a. Membrane behind refractory due to inactivation of Na+ channels and concomitant increase in gk underlying the afterhyperpolarization Factors influencing conduction velocity  Inward Na+ current during AP depolarizes the patch of membrane ahead  If the patch reaches the threshold, it fires and AP  The speed that the AP propagates depends on how far the depolarization ahead of the AP spreads a. This depends on the physical features of the axon Path of least resistance  Narrow axon + many open membrane channels = current flows out through the membrane  Wide axon + few open membrane channels = current flows down inside the axon The farther the current goes down the axon, the farther ahead of the AP the membrane will be depolarized and the faster the AP will propagate AP conduction velocity increases with increasing axonal diameter Myelin  Formed by Schwann cells in the peripheral nervous system and oligodendrytes in the central nervous system  Does not extend continuously  Breaks are nodes of Ranvier  Voltage gated Na+ channels are concentrated at the membrane of the nodes  APs skip from node to node = saltatory conduction Where does AP initiate a neuron  Dendrites and cell bodies do not contain Na+ channels at sufficient density to trigger AP

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Spike initiation zone (SIZ) is part of neuron where Na+ channels are present at sufficient density to create AP in response to membrane depolarisation a. Located in the axon hillock Depolarization of dendrites and soma caused by synaptic inputs from other neurons a. Leads to AP if membrane of the axon hillock is depolarized beyond threshold SIZ is near sensory nerve endings in sensory neurons a. Depolarization caused by sensory stimulation leading to generation of AP that propagate up sensory nerved AP conduct in one direction from SIZ to axonal ending = orthodromic conduction AP propagation in opposite direction (antidromic conduction) elicited artificially in experimental settings

Summary of Information Flow 1. input signal is graded in amplitude and duration proportional to the stimulus 2. SIZ integrates the input signals into a trigger action that produces APs that will propagate along the axon 3. AP are generated if the input signal is greater than the AP threshold 4. once the input signal is above the threshold, any further increase in amplitude of the output signal increases the frequency at which APs are generated (doesn’t affect amplitude) 5. duration of input signal determines the number of APs 6. the graded nature of input signals is translated into a frequency code of APs at the SIZ

Structure of Chemical Synapses in The Brain: Pre and Postsynaptic Mechanisms Neurotransmitters I. Amino acids a. Small organic molecules containing at least one nitrogen atom b. Stored in and released from synaptic vesicles c. Fast synaptic transmission at most CNS synapses mediated by neurotransmitter amino acids i. Glutamate ii. GABA iii. Glycine b. Storage: i. Enzymes convert precursor molecules into neurotransmitter molecules in the cytosol ii. Transporter proteins load the neurotransmitter into synaptic vesicles in the terminal where they are stored II.

Amines (subset of amino acid) a. Small organic molecules containing at least one nitrogen atom b. Stored in and released from synaptic vesicles c. Acetylcholine mediates fast synaptic transmission at all neuromuscular junctions

II.

Peptides a. Large molecules b. Stored in and released from secretory granules i. Frequently observed with synaptic vesicles in the same axon terminals b. Often exist in same axon terminals that contain amine or amino acid neurotransmitters c. STORAGE i. Precursor peptide synthesized in rough ER ii. Precursor peptide split in Golgi apparatus to yield active neurotransmitter iii. Secretory vesicles containing peptide bud off from the Golgi apparatus iv. Secretory granules transported down the axon to the terminal where the peptide is formed

Neurotransmitter release 1. Triggered by AP in the axon terminal 2. Depolarization of terminal membrane causes voltage gated Ca2+ channels in the active zones to open o Membrane channels permeable to Ca2+ with a large inward driving force on Ca2+  Ca2+ flood the cytoplasm of the axon terminal as long as the calcium channels are open 3. Increase in Ca2+ causes neurotransmitter to be released from the synaptic vesicles 4. Vesicles release content via exocytosis into the synaptic cleft o Synaptic vesicle loaded with neurotransmitter o As a response to the influx of Ca2+ through voltage gated calcium channels o Releases its contents into the synaptic cleft by fusion of vesicle membrane with presynaptic membrane

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Eventually recycled by endocytosis

vesicles involved are already docked at the active zones o Involve interactions between proteins in the synaptic vesicle membrane and the action zone In...