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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 V
V


V 
i
g i Ei  I e

i
gi
cm

i
gi
V (t )  V  (V (to )  V ) exp((t  to ) /  V )
Evolution of channel gates
during action potential
Repetitive firing in loligo giant axon
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
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?
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, 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
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
T channels,
Low Threshold Spikes (LTSs),
and bursts
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
Talley, E.M., Cribbs, L.L., Lee, J.H., Daud, A., Perez-Reyes, E., and Bayliss, D.A. J.Neurosci. 19:1895-1911, 1999.
Different burst morphologies in thalamic
neurons: channel gating cannot completely
account for differences
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