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The Hodgkin-Huxley model Equivalent circuit model of a neuron The cell membrane • separates inside and outside of cell • defines voltage difference • separates impenetrable to the flow of ions • stores charge Passive membrane proper8es RC circuits The charge flowing into one element must equal the charge flowing out C R At a junc8on of wires, the total current is zero Across a wire, the poten8al is the same The poten8al changes by a variable amount across a resistor symbol: Ohm: V = IR or I = Vg The poten8al changes by a fixed amount across a baEery symbol RC circuit dynamics Ohm’s law: Capacitor: C = Q/V C R Kirchhoff: Passive membrane Res8ng poten8al: electrochemical equilibrium RC circuits of neurons inside The movement of ions is driven by the Nernst poten8al, R C ENernst outside How does the baEery change the dynamics? Compact cell model (isopoten8al voltage) t Common ionic concentra8ons EK = −75 mV ENa = +55 mV ECl = −70 mV ECa ≈ +150 mV Out of equilibrium • For V > VX current flows into cell: IX > 0 • For V < VX current flows out of cell: IX < 0 • I-V curve (current-voltage): ( IK = γ K V − VK ) RC circuits of neurons inside The movement of ions is driven by the Nernst poten8al, R C ENernst outside Charge is carried by several different types of ions Mul8ple kinds of ions Several I-‐V curves in parallel: New equivalent circuit: How does the cell actually behave? The ac8on poten8al Methods: Squid giant axon Methods: Voltage clamp Currents are voltage-gated, so must control voltage Methods: Voltage clamp Capacitive current when applying voltage command Inward and outward currents when depolarizing Separa8on of currents Two sources of voltage dependence ( ) INa V, t ( ) = g Na V, t = ( ) ( g Na V, t i V − VNa conductance ( ) INa V, t V − VNa ) driving force ( ) g K V, t = ( ) IK V, t V − VK Measuring conductances • INa activates, then inactivates • IK has shallow S-shaped activation, but exponential inactivation Temporal dynamics • Ansatz: ( ) ( ) g K V, t = g K n V, t decay: () ( 4 n t exp − t τ ) Ac8va8on variable: n(V,t) • For a fixed voltage, V: τn () dn t dt = () n∞ − n t Temporal dynamics • Rise: 1.0 Activation Variable 1.0 Activation Variable • Decay: 0.8 0.6 n 4 n 0.4 0.2 n 4 n 0.8 0.6 0.4 0.2 0.0 0.0 0 1 2 3 Time (s) 4 5 0 1 2 3 Time (s) 4 5 Equa8ons for the ac8ve currents • Conductances: gK = gK n4 3 g Na = g Na m h • Currents: ( IK = g K V − VK ( ) INa = g Na V − VNa ) PuTng all the channels together dV C = − g L V − VL − g K n 4 V − VK − g Na m3 h V − VNa + I ext dt ( ) ( ) ( ) Current (µA/cm^2) Results: single spike 20 0 40 Voltage g_Na g_K Voltage (mV) 20 30 0 20 -20 -40 10 -60 -80 0 3 4 5 6 7 8 9 Time (ms) 10 11 12 13 Conductance (mmho/cm^2) 40 Current Results: activation variables 20 0 Voltage (mV) 40 20 0 -20 -40 -60 -80 0 5 10 15 Time (ms) 20 Activation Variable 1.0 25 n m h 0.8 0.6 0.4 0.2 0.0 0 5 10 15 Time (ms) 20 25