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16: Neuron Physiology

16: Neuron Physiology. Canisius College Bio 112 Jason Mayberry. Overview of Neuron Anatomy and Function. Dendrites : Receives input from outside stimulus (senses or other nerves); Propagates Graded Potentials. Axon Hillock:

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16: Neuron Physiology

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  1. 16: Neuron Physiology Canisius College Bio 112 Jason Mayberry

  2. Overview of Neuron Anatomy and Function Dendrites: Receives input from outside stimulus (senses or other nerves); Propagates Graded Potentials Axon Hillock: Beginning of the axon where Graded Potentials converge and are converted to an Action Potential (Trigger Zone) Axon: Carries the signal away from the cell body toward some target (other nerves or effectors such as muscles); Propagates Action Potentials Terminal Branches: Branching at the end of an axon which are responsible for passing the signal to the target, usually by releasing signaling molecules called neurotransmitters into a synapse. Axon Collateral Rare branches off of an axon. Soma: Neuron Cell Body containing the Nucleus which manufactures all molecules needed for the neuron. • Neurons: Cells with long extensions that carry information from stimulus to target via electrical signals and elicit a response through the release of neurotransmitters (paracrine signals) • Graded Potentials: electrical currents initiated by a stimulus; vary in size; degrade in time/space • Action Potentials (APs): electrical currents initiated by graded potentials at the axon hillock; all or nothing; do not degrade; vary in frequency. • Basis of All Decisions: Axon Hillock determines if Graded Potentials at any time are sufficiently strong to generate an Action Potential. • Information flow: Size of Graded Potentials  Frequency of AP  Amount of Neurotransmitter

  3. Voltage and Electricity Na+ Na+ Na+ Na+ Na+ Na+ Na+ ++++++++++++++ – – – – – – – – – – – – Na+ Na+ Na+ Na+ Na+ Na+ Na+ • Electrical Current • Movement of ANY charged particle • Lightening: usually electrons moving clouds ↔ground • Batteries: electrons moving +  – end • Cells: ions such as Potassium (K+) and Sodium (Na+) relative to membrane • Membrane is a good insulator, but channels add permeability • Voltage • Potential Energy which can make a charged particle move • Membrane Potential: voltage which causes an electrical current to flow relative to a membrane. • Chemical Potential (C): • Voltage resulting from a concentration difference • Diffusion of ion constitutes an electrical current • Electrical Potential (E): • Voltage resulting from a spatial imbalance in charged particles across the membrane. • Current results from “+” ions moving toward “–”, and vice versa • Electrochemical Potential (E + C): • Voltage resulting from the balance between electrical and chemical potentials • E. and C. may be cooperative or antagonistic • Direction and size of the current depends on the balance between the E. and C. Extracellular Potential of Na+ Ion Na+ C E Na+ Intracellular

  4. Sodium/Potassium Pump Cl– Cl– Cl– Na+ Na+ Na+ Cl– Na+ Cl– Na+ Na+ Cl– 3 Na+ Cl– Na+ Na+ Cl– Na+ Na+ Cl– Cl– C E K+ K+ A– K+ A– C E A– K+ A– 2 K+ K+ K+ K+ A– A– A– • Primary Active Antiporter (uses ATP energy) • 2 K+ pumped into the cell • 3 Na+ pumped out of the cell • Builds strong opposing Chemical Potentials for Na+ and K+ • Relatively Little Electrical Potential results from the Sodium Potassium Pump • Note: Positive Charges are mostly balanced by Anionic Proteins and Phosphate ions (A–) Inside, and Chloride Ions (Cl–) Outside • Transport channels are needed for the ions to diffuse back across the membrane. Potential of Each Ion Extra-cellular ATP Intra-cellular

  5. Variety of Pumps • Cells have many types of pumps that move a variety of ions in and out of the cell • Some pumps are found in all cells/ others contribute to cell specialization • Only pumps that create an electrical disequilibrium are electrogenic • Ion concentrations in cells depends on the type and number of different pumps. Electrogenic Typical Neuron Concentrations Na/K Pump Ca Pump Na-Ca Exchanger Chloride Pump NKCC Symporter K+ 5mM Na+ 145mM Cl– 108mM Ca2+ 1mM Cl– 2Cl– 3Na+ Ca2+ Na+ K+ HCO3 – Ca2+ Ca2+ ATP ATP ATP K+ 150mM Na+ 15mM Cl– 10mM Ca2+ 0.0001mM Cl– 2K+ Kidneys, Secretory Cells, and others. Often with opposite orientation 3Na+ 3Na+ Red Blood Cells ATP Smooth ER Ca2+

  6. Leaky Channels and Gated Channels • Various Pumps generate chemical potentials for many ions. • Phospholipid bilayers strongly resist ion movement, and are thus good insulators • Membrane is made permeably by various channels (leaky and gated) that allow ions to flow across the membrane • Membrane permeability to each ion is proportional to the number of open channels. • What is the effect of ion movement across the membrane? “Sense-stimulus” gated Channels Ligand gated Channels Typical Neuron Concentrations Voltage Gated Channels Leaky Channels K+ 5mM Na+ 145mM Cl– 108mM Ca2+ 1mM K+ Na+ Cl– Ca2+ K+ 150mM Na+ 15mM Cl– 10mM Ca2+ 0.0001mM Na+ Na+ Na+ K+

  7. Leaky K+ Channels Equilibrium Potentials • Assume • Chemical potential due to ion concentration gradients • “+” and “-” charges inside and outside balanced; net charge is “0”. • Movement of ions through channels results in: • A current while the ion is moving. • Insignificant depletion of chemical potential (assuming a large gradient) • A charge difference (electrical potential) whose effect on the ions movement is opposite to the concentration gradient. • As more ions move, the charge gets larger until it prevents further movement • Equilibrium Potential: the electrical potential of a permeable ion when its electrical potential and chemical potential are balanced. • electrical potentials built faster than chemical: • 1 of every 1000K+ ions moving  Δ100mV • Larger concentration gradients generate larger equilibrium potentials. • All ions affect (if permeable) and are effected by the membrane potential. • The electrical potential is reported as the size of the difference inside relative to out (i.e. 0 outside and -6 inside) Potential Na+ Relative Net Electrical Charge Extracellular Na+ Na+ Na+ C E Na+ +11 -9 +2 +10 -9 +1 +12 -9 +3 +9 -9 0 Na+ Na+ Na+ Na+ Na+ Leaky K+ Channel K+ K+ K+ C E +5 -6 -1 +3 -6 -3 +4 -6 -2 +6 -6 0 K+ K+ K+ K+ -6mv difference K+ K+ K+ Intracellular Membrane Potential (Resulting from diffusion of K+) 0 0 Electrical Potential Strength Volts Volts Equilibrium Potential resulting from K+ movement A larger initial concentration gradient results in a larger equilibrium potential Chemical Potential Strength

  8. Determining the Equilibrium Potential of an Ion • Nernst Equation: a formula for calculating the equilibrium potential for a single +1 ion given the concentrations in and out of a cell. • …tells the relative strength of the Chemical Potential for any ion in terms of the ion’s equilibrium potential Where: =ion concentration Equilibium Potential of K+Ion Equilibium Potential of Na+Ion Na+ 150 mM Extracellular Extracellular 5 mM K+ Na+ 15 mM C C E E −89.7 mV +62.0 mV ? ? 140 mM K+ Intracellular Intracellular Equilibrium Potential for K+ Equilibrium Potential for Na+

  9. Measuring Membrane Potential • Live axons placed in a solution mimicking extracellular fluid • Electrodes • 1 placed in the extracellular fluid • 1 stabbed through the plasma membrane of the axon • The extracellular electrode is set arbitrarily to zero. • Membrane potential measured as the potential difference between the two electrodes. • The membrane potential of a typical neuron measures around -70mV • Equilibrium Potential of K+ = -89.7mV • Equilibrium Potential of Na+ = + 62.0mV • How can we account for the actual membrane potential? +20 Microelectrode 0 -20 Membrane potential (mV) -40 -60 -80 Time(s) Squid giant axon Voltmeter Squid giant axon  +  Microelectrode placed outside the cell + + + +  +  + + + + + +  + + +  + + + +   + + + +  +  + + + + + + + + + + +   + +     +  +    + + + +  +   + +  + + +   + Microelectrode placed inside the cell  +       +  + + + +  + + +    + +  + +   +     + + +   + + + + +    

  10. Leaky K+ Channels and the Resting Membrane Potential Potential • Passive (Leak) K+ Channels • Numerous K+ leak channels throughout neuron • Alone would bring membrane to K+ Equilibrium • Passive (Leak) Na+ Channels • 1/50th as common as K+ channels throughout neuron • Imagine cell at K+ equilibrium potential • Na+ current makes membrane slightly less negative • Allows additional K+ to leave • Resting Membrane Potential • Dynamic, steady-state membrane potential resulting from movement of K+, and to a lesser extent Na+, through leaky channels • weak current resulting from back and forth constant Na+ and K+ diffusion • Na/K Pump maintains concentration gradient. • E and C Potential on K+ are opposite and ~equal • E and C potentials bothgiveNa+ a large potential to move into the cell. • Sets the stage for Na+ to rush into the cell with gated Na+ channels! Extracellular Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ C E Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Leaky K+ Channel Leaky K+ Channel Leaky Na+ Channel ATP K+ C E K+ K+ -70 -90 K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Intracellular • Equilibrium Potential of Na+ is ≈ +62mV 0 Resting Membrane Potential ≈ -70 mV Volts • Equilibrium Potential of K+ is ≈ -90mV

  11. All Cells Have a Resting Membrane Potential All cells have a resting membrane potential of variable size, but only nerves and muscles are excitable (use them to conduct electrical currents)

  12. Changes to the Resting Membrane Potential Depolarization 0 0 Voltage Voltage Resting Resting • Increasing permeability of the membrane (i.e. via opening additional ion channels) allows these ions to diffuse across the membrane, creating a current which ultimately alters the Membrane Potential. • Hyperpolarization • Increasing the size of the Membrane Potential (making it more negative) • Moving negative charged ions into the cell (opening Cl- channels, not common) • Moving positive charged ions out of the cell (opening extra K+ channels) • Depolarization • Decreasing the size of the Membrane Potential (making it less negative) • Moving negative charged ions out of the cell (Not common) • Moving positive charged ions into the cell (K+ or Ca2+) • Overshoot: The part of a depolarization where the inside of the cell becomes positively charged. Extracellular Cl– Ca2+ Na+ Hyperpolarization –––––––––––––––––––––––––––––––––––––––––––––––––– Proteins– K+ Intracellular

  13. Graded Potentials Extracellular Na+ Na+ Resting Potential Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ 3Na+ Na+ Na+ +60 +60 Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ C E Na+ +30 +30 Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Passive K+ Channel 0 0 ATP -70 -50 +10 -20 -30 -30 K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ -60 -60 C E K+ K+ K+ K+ K+ K+ K+ K+ K+ 2K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Intracellular K+

  14. Graded Potentials • Sensory stimulated gated Na+ channels (typically) are found on dendrites and soma. • Most external stimuli cause Na+ gates to open allowing Na+ to flow in which causes a local membrane depolarization • Larger stimuli cause more channels to open and stay open longer, resulting in a larger depolarization • If gated channels allow negatively charged ions to flow in, a hyperpolarization results • Graded Potential: Na+ diffuses very quickly away from the channel spreading the depolarization towards the axon hillock. • The Size of depolarization decreases with time and distance due to: • Dilution of Na+ as it spreads out • Cl- ions which diffuse into the cell • Na+/K+ pump returning Na+ to extracellular fluid Extracellular Na+ Na+ Resting Potential Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ 3Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ C E Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Passive K+ Channel ATP -70 +10 -20 -50 K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ C E K+ K+ K+ K+ K+ K+ K+ K+ K+ 2K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Intracellular K+

  15. Overview of Neuron Anatomy and Function Dendrites: Receives input from outside stimulus (senses or other nerves); Propagates Graded Potentials Axon Hillock: Beginning of the axon where Graded Potentials converge and are converted to an Action Potential (Trigger Zone) Axon: Carries the signal away from the cell body toward some target (other nerves or effectors such as muscles); Propagates Action Potentials Terminal Branches: Branching at the end of an axon which are responsible for passing the signal to the target, usually by releasing signaling molecules called neurotransmitters into a synapse. Axon Collateral Rare branches off of an axon. Soma: Neuron Cell Body containing the Nucleus which manufactures all molecules needed for the neuron. • Neurons: Cells with long extensions that carry information from stimulus to target via electrical signals and elicit a response through the release of neurotransmitters (paracrine signals) • Graded Potentials: electrical currents initiated by a stimulus; vary in size; degrade in time/space • Action Potentials (APs): electrical currents initiated by graded potentials at the axon hillock; all or nothing; do not degrade; vary in frequency. • Basis of All Decisions: Axon Hillock determines if Graded Potentials at any time are sufficiently strong to generate an Action Potential. • Information flow: Size of Graded Potentials  Frequency of AP  Amount of Neurotransmitter

  16. Voltage Gated Channels and Action Potentials + + + + + + – – – – – – + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – • Axon Hillock (“The Trigger Zone”): • “Processes” Graded potentials which are strong enough to reach it • Converts Graded Potentials to Action Potentials if the Graded Potential depolarization(s) are large enough. • Contains high numbers of voltage gated Na+ and K+ channels, which are also found along the length of the axon • Voltage Gated Na+ channels: Na+ channels which open when membrane depolarization crosses a threshold (around -50mV) • Activation Gate: on the outside portion; opens quickly when stimulated, then closes when the cell starts to re-polarize • Deactivation Gate: on the inside portion; open at rest but closes slightly after the Activation gate opens, then reopens when resting membrane potential is re-established; prevents Action Potential from traveling backward (see Refractory Period) • opening one voltage Na+ channel creates positive feedback which further depolarizes the membrane, ensuring that all Na+ channels open in a given area of the membrane. • Causes a sharp local depolarization in the membrane making membrane positive relative to outside • Voltage Gated K+ channels: K+ channels which open at same threshold as Voltage Gated Na+ channels • Gate opens after a short delay (while the voltage Na+ channel is still open), then closes slowly (after the Na+ is already closed) • Re-polarizes the membrane, including a brief hyperpolarization. • Action Potential: Currents resulting from ions movement sequentially through adjacent membrane via voltage gated channels • ALL OR NOTHING (due to positive feedback from Voltage Gated Na+ Channels; size depends on gradient and # of channels) • Travels along the length of the axon as Na+ diffuses to neighboring channels causing them to open • Travels more slowly than graded potentials but does not degrade • Only ~1/1000thof the concentration gradients are depleted with each Action Potential Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ + – – – + – + – + + + Na+ – – – + – + – + – – – Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

  17. Graded vs Action Potentials + + + + + + – – – – – – + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – • Graded Potentials • Fast Conduction along membrane • Vary in size with stimulus strength, temporally, and spatially • Action Potentials • Slow conduction through and along membrane • Positive feedback reinforces the initial stimulus so all are maximal +60 +60 +60 +60 +30 +30 +30 +30 Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ 0 0 0 0 Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ + – – – + – + – + + + Na+ -30 -30 -30 -30 -60 -60 -60 -60 – – – + – + – + – – – Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

  18. Figure 48.12-3 Axon Plasma membrane Action potential Cytosol Na+ Action potential K+ Na+ K+ Action potential K+ Na+ K+

  19. Overview of Neuron Anatomy and Function Dendrites: Receives input from outside stimulus (senses or other nerves); Propagates Graded Potentials Axon Hillock: Beginning of the axon where Graded Potentials converge and are converted to an Action Potential (Trigger Zone) Axon: Carries the signal away from the cell body toward some target (other nerves or effectors such as muscles); Propagates Action Potentials Terminal Branches: Branching at the end of an axon which are responsible for passing the signal to the target, usually by releasing signaling molecules called neurotransmitters into a synapse. Axon Collateral Rare branches off of an axon. Soma: Neuron Cell Body containing the Nucleus which manufactures all molecules needed for the neuron. • Neurons: Cells with long extensions that carry information from stimulus to target via electrical signals and elicit a response through the release of neurotransmitters (paracrine signals) • Graded Potentials: electrical currents initiated by a stimulus; vary in size; degrade in time/space • Action Potentials (APs): electrical currents initiated by graded potentials at the axon hillock; all or nothing; do not degrade; vary in frequency. • Basis of All Decisions: Axon Hillock determines if Graded Potentials at any time are sufficiently strong to generate an Action Potential. • Information flow: Size of Graded Potential  Frequency of AP  Amount of Neurotransmitter

  20. Refractory Periods and the Strength of Stimulus Absolute Refractory Period Relative Refractory Period Stimulus Start The size of the arrow indicates the strength of the stimulus Stimulus Stop Membrane Potential Time • Refractory Period: time following an Action Potential during which a second AP does not occur in spite of stimulus which normally would. • Absolute Refractor Period • Time during which Na+ voltage gates are open or the deactivation gate is still closed. • No new Action Potential can be Generated no matter how large the stimulus • Ensures that each peak is a discrete event • Prevents the APs from going backward • Relative Refractory Period • Begins before/with Undershoot and ends when Resting Potential and normal Threshold is restored. • Membrane potential is farther from threshold, which may also be elevated, so only larger stimuli can trigger an AP • AP’s generated during this time may have a lower peak • Stimulus Strength • AP magnitude is constant so it does not change with stimulus strength (unlike graded potentials); all AP’s are “all-or-nothing” • Stronger Stimuli cause more frequent APs during the Relative Refractory Period Threshold

  21. Action Potential and Refractory Period Absolute Refractory Period Relative Refractory Period • Note: at any local along the membrane there are multiple VG channels acting at the same time but not in perfect unison. • The illustration here should be considered the average of all local channels +30mV 0mV Thr. -70mV Voltage Gated Channels K+ Relative Conductance Na+ -0.5 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5

  22. Action Potential (putting it all together) Repolarization Threshold for the voltage gated channels; AP is all or nothing. Overshoot Hyper-polarization(Undershoot) Resting Membrane Potential results from passive movement of K+ and Na+ Chemical gradient of K+ and Na+ established by Na/K pump Summation of Graded Potentialsfrom external stimulus Repolarization (Down-Stroke) Voltage Gated K+ channels return the cell to resting potential Depolarization (Up-stroke) Voltage Gated Na+ channels reverse the polarity of the local membrane Leaky Channels Voltage Gated Channels Na/K Pump K+ K+ 3Na+ Extracellular ATP Intracellular Na+ Na+ 2K+ +100 0 Voltage -100

  23. Ion Movements, Channels, and Potentials 3 Na+ 3 Na+ 3 Na+ 3 Na+ Na/K Pump Stim or NT Gated Voltage Gated ElectrochemicalPotentials(at the beginning of each phase) Leaky K+ K+ Na+ C E C E Rest Na+ 2 K+ K+ K+ K+ K+ Na+ C E C E +100 Stimulus U Na+ Na+ Na+ Na+ 2 K+ 2 K+ 2 K+ Voltage 0 S D K+ Na+ R R C E C E Upstroke -100 Na+ K+ K+ Na+ C E C E Downstroke

  24. Neuron Races • Imagine identical neurons generating Action Potentials at the Axon hillock and racing depolarizations down the axon. • #1 has Voltage Gated Channels ( ) along the axon and propagates APs along the length of the axon • #2 only has VG Channels at the axon hillock, so the depolarization travels only as a graded potential down the axon. • #3 only has VG Channels at the axon hillock, but has insulation that slows the decay of the graded potential. • #4 has insulation with periodic gaps where VG channels recharge the depolarization. Start 1 2 3 4 5 Finish Depolar-ization Depolar-ization 3 4 2 1 z Depolar-ization Depolar-ization

  25. Continuous vs Saltatory Conduction • Continuous Conduction: • Conduction of APs in non-insulated (i.e. non-myelinated) neurons where APs are generate along the entire length of the axon • Slow • Many neurons (most in humans) are insulated in-between recharging points along the axon. • Myelin: neuron insulation formed by supporting cells that wrap their membrane around the axon • Node of Ranvier: gaps between insulated regions of the neuron where Voltage Gated Channels recharge the depolarization • Saltatory Conduction: • Signal travels quickly from node to node via graded currents • APs generated only at Nodes of Ranvier (recharge depolarization) • APs appear to “jump” from Node to Node • Fast Depolar-ization Myelin Cell Axon 1 4 Node of Ranvier Myelin Depolar-ization Graded Graded Graded AP AP AP

  26. Axon Diameter and the rate of AP conduction • Axons with a larger diameter pose less resistance to the flow of ions resulting in faster conduction of Graded and Action Potentials. • In organisms with complex nervous systems, myelination allows axon diameter to remain small to accommodate the presence of more axons. • Slowest: Small diameter no myelination • Faster: Large diameter no myelination • Faster Still: Small diameter with myelination • Fastest: Large diameter with myelination

  27. Demyelinating Diseases Node 1 Node 2 Myelin sheath Node of Ranvier Na+ Depolarization Demyelinating diseases such as Multiple Sclerosis reduce or block conduction when current leaks out of the previously insulated regions between the nodes. Degenerated myelin sheath Na+ Current leak reduces conduction.

  28. Synapses Axodendritic Axosomatic Axoaxonic • Synapse = “To clasp or join” • A junction that mediates information transfer from one neuron to the next neuron, muscle, or gland • Can transfer electrical signal (electrical synapse) or through chemical messengers (chemical synapse) • Presynaptic Neuron: Neuron conducting the AP towards the synapse • Postsynaptic Neuron: Neuron conducting signal away from the synapse • Most cells synapses with 1000 to 10,000 other neurons, but can be >200,000.

  29. Degree of Synapsis Axon terminals of presynaptic neurons The cell body of a somatic motor neuron is nearly covered with synapses providing input from other neurons. Dendrite of postsynaptic neuron Glial cell processes Axon

  30. Electrical Synapse Action Potential Action Potential Gap Junctions Pre-Synaptic Neuron Post-Synaptic Neuron • Gap Junctions allow ions to pass from one the terminal end of one axon to another cell, continuing the propagation of the AP. • Found in CNS • Fast but do not allow processing of information as do Chemical Synapses. • Important for arousal from sleep, mental attention, conscious perception, jerky movements of the eyes., • Common during embryonic development where they develop into more sophisticated chemical synapses.

  31. Chemical Synapse Synaptic Cleft Ligand (Neurotransmitter) Gated Ion Channel Post Synaptic Potential (Graded) travels towards the Axon Hillock Action Potential Voltage Gated Ca2+ channels Synaptic Vesicle with Neurotransmitter Pre-Synaptic Neuron Post-Synaptic Neuron Ca2+ Ca2+ Ion Ca2+ Ion Ion Ca2+ Ca2+ • AP reaches Axon Terminal • Voltage gated Ca2+ channels open and let Ca2+ into the cell • Ca2+ causes synaptic vesicles with neurotransmitter to move to and fuse with the plasma membrane • Neurotransmitter travels across the synaptic cleft • Binding of Neurotransmitter to Receptors (Ligand Gated Ion Channels) causes them to open • If Na+ or Ca++ enter then a depolarization results (an EPSP) • If K+ exits or Cl- enters, then a hyperpolarization results (an IPSP) • The Neurotransmitter is quickly broken down or pumped back into the presynaptic neuron • The closer the APs are the more neurotransmitter will be released and the larger the Post Synaptic Potential will be. • Synaptic Delay: The time taken for a signal to be transmitted via Chemical Synapses is the “rate limiting step” in signal conduction.

  32. Neurotransmitter Classes • Different Types of Neurotransmitters • Acetylcholine • Biogneic Amines (Norepinephrine, Dopamine, Serotonin, Histamine) • Amino Acids • Peptides • ATP • Dissolved Gasses (NO, CO) • Lipids (Eicosanoids/Cannabinoids) • Categorizing by Location: Generally found at specific types of synapses (i.e. Acetylcholine is always found at neuromuscular synapses) • Categorizing by Effect • Some always generate EPSPs • Some Always generate IPSPs • Some can generate either, depending on where they are found • Categorizing by Mechanism of Action • Some cause ion channels to be opened directly • Some use Cytosolic “second messengers” to open channels (may have a longer term effects)

  33. “EPSP vs. IPSP” and Summation Threshold Resting Threshold Resting Threshold Resting • Graded Potential can be either a Depolarization or a Hyperpolarization • If Neurotransmitters causes Ca2+ or Na+ channels to open the membrane will be Depolarized • If Neurotransmitters cause K+ or Cl– channels to open the membrane will be Hyperpolarized Total stimulus must be +15mv from resting -55 • Excitatory Post Synaptic Potentials (EPSP): Post synaptic potentials that result in Depolarizations and thus contribute to the generation of a new AP. • Inhibitory Post Synaptic Potentials (IPSP): Post synaptic potentials that result in Hyperpolarizations and thus inhibit the generation of a new AP • Effect of all Post Synaptic Potentials are summed at the Axon Hillock • Temporal Summation: 2 Graded Potentials arrive from the same dendrites in close succession • Spatial Summation: 2 Graded Potentials arrive from different dendrites at the same time • If total of all Post Synaptic Potentials cause the Membrane Potential to broach threshold a new AP will be generated. -70 Temporal Summation -55 -70 Negative Spatial Summation -55 -70 Positive Spatial Summation

  34. Information Processing How is the information regarding the strength of a stimulus communicated along different parts of a neural pathway, beginning with the initiation of a stimulus in the dendrites an interneuron (i.e. it is receiving multiple inputs from separate neurons) through to the dendrites of the next post-synaptic neuron? Dendrites Axon Hillock Axon Synaptic Cleft Dendrites Size of Graded Potential Summation of Graded Potentials Frequency of Action Potentials Amount of Neurotransmitter Size of Graded Potential 0 Strong Stimulus 0 Weak Stimulus

  35. Nervous System Organization Canisius College Bio 112 Jason Mayberry

  36. Neural Cells 1) Neurons: Communicate via electrical signals Spinal cord Brain Spinal cord 2) Glial Cells (Neural Support Cells) Interneuron Motor Sensory

  37. Variation in Neuron Structure (FYI) CNS and Motor Sensory Sensory neuron Interneuron Motor neuron

  38. Neuron Support Cells Astrocytes: • Foot processes surround blood vessels as part of blood-brain barrier • Take glucose from the blood and deliver pyruvic acid to neuron • Aid in development • Source of neural stem cells • “Mop-up” leaked ions and stray molecules in the extracellular space. • Signal to other astrocytes and neurons Oligodendrocytes: • Myelin for most CNS neurons • Highly Branched; one cell form myelin around multiple neurons. Eppendymal: • line the ventricles (cavities) of the CNS, help circulate cerebrospinal fluid in the ventricles. • Source of neural stem cells Microglia: Health Monitors; Macrophages of the CNS Schwann Cells: • Myelin for a majority of axons in the PNS • Each cell wraps around just part of a single axon Satellite (Non-myelinated Schwann cell): • Found among groups of cell bodies (ganglia). • Form supportive capsules around soma Glial (Neuroglial) cells support and service function of neurons in both the CNS and the PNS CNS PNS

  39. Cells of the Nervous System CNS PNS VENTRICLE Astrocyte Ependy-malcell Oligodendrocyte Cilia Schwanncells Capillary Neuron Microglial cell

  40. Structural and Functional Organization of the Nervous System Somatic:Conscious movement of skeletal muscles Somatic (Conscious) Central Nervous System (CNS)Brain and Spinal Chord Processes information Peripheral Nervous System (PNS)All Neurons extending to and from the CNS Motor (Efferent) Nerves Receive directions from the CNS and elicit response from specific targets Sensory (Afferent) Nerves Gather information and sends it to the Central Nervous System Autonomic:Unconscious, homeostatic responses of cardiac, smooth muscles, and glands Para-Sympathetic“Rest and Digest” Sympa-thetic“Fight or Flight” VisceralInternal Organs (mostly uncon-scious)

  41. Autonomic Nervous System Sympathetic Parasympathetic • "Fight or Flight" • Excitement, Emergency, Exercise, Embarrassment • Routes energy resources to brain, heart, and skeletal muscles. • Picture yourself running away from a lion, tiger, or bear (Oh my!) • "Rest and Digest" • Digestion, Defecation, Diuresis. • Reduces energy use and directs "Housekeeping" activities. • Picture yourself sitting in a recliner and reading after eating a big meal. • Dilates pupils • Constricts pupils • Inhibits salivation • Stimulates salivation • Increases heartbeat and • force of contraction • Slows heartbeat Cranial nerves • Relaxes airways • Constricts airways • Stimulates digestion and stomach activity • Inhibits digestion and stomach activity Celiac ganglion • Increases glucose utilization by liver cells; stimulates insulin secretion from pancreas • Stimulates release of glucose into the blood; inhibits insulin release from pancreas • Increases activity of small intestines to promote absorption of nutrients • Inhibits activity of small intestines • Stimulates secretion of epinephrine from adrenal medulla Inferior mesenteric ganglion • Stimulates urinary bladder to contract Sympathetic chain ganglia • Relaxes urinary bladder • Promotes ejaculation and vaginal contractions • Promotes erection of genitals

  42. Functional Divisions of the Nervous System Somatic Central Nervous System (Brain and Spinal Chord)Neural Processing and Integration Afferent (Peripheral Nerves) Efferent (Peripheral Nerves) Effective Nervous System Sensory Neurons: PNS Afferent Neuron Motor Neuron: PNS Efferent Neuron Interneurons: Neurons entirely within the CNS Visceral

  43. Peripheral Nervous System Organization Sensory Ganglion (Dorsal Root Ganglion) Ganglia: Clusters of Neuron Cell Bodies in the Peripheral Nervous System Somatic Sensory Sympathetic Ganglion(Chain Ganglion) Sympathetic Parasympathetic Axon Myelin Nerves: Bundles of axons in the peripheral Nervous System Connective Tissue Vasculature

  44. Divisions of the CNS Metencephalon Neurulation causes the hollow neural tube to form Different Regions of the neural tube are specified to form different regions of the Central Nervous System Mesencephalon Diencephalon Myelencephalon Telencephalon Spinal Chord • Diencephalon • Contains Thalamus, Hypothalamus, Epithalamus, and the Pituitary • Pre-Processing of sensory information • Integration of Autonomic NS and the Endocrine system Cerebrum (Telencephalon) Consciousness • Brain Stem • Divided into the • Midbrain (Mesencephalon) • Pons (Metencephalon) • Medulla Oblongata (Myelencephalon) • Pathway for nerves connecting Cerebrum, Cerebellum, and Spinal Chord • Maintains respiratory and cardiovascular rhythms, and other autonomic “reflexes” • Cerebellum (Metencephalon) • Integrates proprioception (self-perception) and Motor responses to ensure effective motor activity. • Does not initiate motor activity on its own, only communicates with the Cerebral centers responsible for these movements. • Spinal Chord • Reflex activity • Tracts leading to and from the brain.

  45. Lobes and Divisions of the Cerebrum • Surface Anatomy of the Brain • Gyrus = top of fold • Sulcus = shallow groove • Fissure = very deep groove • The Cerebrum is divided into anatomically and functionally distinct regions by major folds on its surface. Gyrus Sulcus Fissure Central Sulcus Parietal Lobe Frontal Lobe Anterior Parieto-Occipital Sulcus Left Hemisphere Right Hemisphere Occipital Lobe Lateral Sulcus Transverse Cerebral Fissure Temporal Lobe Longitudinal Fissure Insular Lobe(Insula)

  46. Grey and White Matter in CNS Brain Midbrain Pons Medulla Oblongata Spinal Chord • Grey Matter: Where cell bodies are found in the CNS • Cerebral Cortex: outer most darker layer of the cerebrum (folding increases surface area) • Nuclei discrete collections of cell bodies deep with the cerebrum (e.g. Hypothalamic Nuclei) and lower parts of the brain • White Matter: Collection of myelinated axons in the CNS (no connective tissue) • Fibers connecting different parts of the cerebrum • Tracks in the Brain Stem and Cerebellum • Ascending and DescendingTracks in the Spinal Chord

  47. Variable Stimuli for the Nervous System “Five External Senses” (Somatic Sensory) Sight Sound Smell Taste Touch Light Bending of cilia on hair cells in cochlea Molecules in the air Molecules in food Pressure or Vibration Internal Stimuli Equilibrium Proprioception Somatic Visceral +Others… Contracted Relaxed Bending of cilia on hair cells in ear canals Stretch/Contraction state of Blood Vessels and Digestive Organs Stretch/Contraction state of muscles

  48. Targets and Effects Elicited by Nervous System • Neuronal release of Neurotransmitter Elicits Different Responses in Different Tissues Neuronal Target e.g. Sensory Neurons targeting neurons in the Spinal Chord, then brain. Muscle Target e.g. Skeletal Muscle for movement; Iris for Pupil Dilation, etc Glandular Target e.g. Adrenal Medulla for Secretion of Epinephrine ion Na+ Na+ Na+ Na+ Na+ Na+ ion ion Muscle Contraction Secretion IPSP or EPSP

  49. Reflexive vs Conscious Response Sensory (Afferent) Neuron:sensitive to changes in the internal or external environment; Sends Action Potentials to the CNS Effector Organis responsible for the physical response (muscle or Secretory gland) Motor (Efferent) Neuron Transmits info from CNS to the Effector Organ Ouch! CNS Processing Center:Responsible for generating a meaningful response (either Reflex or Processed); Brain and Spinal Chord. Interneuron: entirely within CNS; links Sensory and Motor Neurons Nerve Tract leading to the brain for more complex processing And/Or back to effectors muscle to create a reflex. Stimulus Click Here

  50. Reflex Arc: Stretch Reflex Afferent Signal Contraction Stimulus Reflex Arc Efferent Signals Relaxation

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