Nens220, Lecture 5 Beyond Hodgkin-Huxley John Huguenard Stanford University

Integrating with multiple conductances Use parallel conductance model to determine V and dynamic membrane time constant tV

Evolution of channel gates during action potential

Repetitive firing in loligo giant axon Stein, 1967 modelling results from hh equations, confirmed results of Hagiwara & ohuri, 1958, at warmer temps, repetitive spikes are actually from at tcr cell. Loligo forbesi , eastern atlantic and mediteranean Stein, 1967

Summary of equilibrium states and time constants for HH gates

Voltage gated channel dynamics Courtesy W Lytton

A new K current, distinct from delayed rectifier Cal bar is estimated at about 300 ms in right column, and about 30 ms in left Connor & Stevens, 1971

IA is dependent on resting potential

Extraction of IA from total IK

Simulations with I-A reproduce spike trajectories

A role for IA in spike propagation? Lobster walking axons have I-a, but do cortical cells, organotypic slice culture Debanne et al 1997

Differential regulation of branches Debanne et al 1997

Calcium indicator & axons

M current, a slowly-activating and inactivating current Brown and adams nature 1980, m current, figure 1 Brown and Adams, 1980

Molecular identity of M current Wang et al 1998

Antagonists of M current alter spike firing Wang et al 1998

Luthi & McCormick 1998, neural resonators Luthi 1998, fig 1

Parallel conductance model, Hodgkin and Huxley

Thalamic relay neurons have state dependent firing modes McCarley, Benoit & Barrionuevo, J. Neurophysiol, 50:798, 1983. Hirsch, Fourment & Marc, Brain Res. 259:308, 1983

Properties of the low threshold spike Llinás and Jahnsen, Nature 297:406

Paradoxical excitability in thalamic relay neurons -55 through –75 mV

T channels, Low Threshold Spikes (LTSs), and bursts Cultured enteric neurons, pair recordings. 0.5 Hz gives fast cholinergic responses that fade at higher frequencies and are replaced by VIP dependent slow EPSCs, but only at frequencies > 5 Hz. Action potential (High-threshold Na+ spike) Low-threshold Ca2+ spike Regular Firing Burst Firing Huguenard, JR TINS 21:451-452, 1998

b Vm –55 mV Vm –75 mV

Availability of T channels

T type calcium channel genes in thalamus A1g in dt, ai,h in nrt , leads to differences in bursts A1g yellow, a1h red, a1i blue

Different burst morphologies in thalamic neurons: channel gating cannot completely account for differences How and why? e.g., VB

IT has slow kinetics in nRt cells: ITs

The H current (aka the q current): Hyperpolarization induced depolarization McCormick & Pape, J Physiol 1990 431:291

The H current, slow kinetics McCormick & Pape, J Physiol 1990 431:291

The H current, activation via hyperpolarization McCormick & Pape, J Physiol 1990 431:291

The H current, susceptible to neuromodulation McCormick & Pape, J Physiol 1990 431:3191

The H current, highly expressed in dendrites of principal (excitatory) cortical neurons Magee 1998 J Neurosci 18:7613