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

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

3. Evolution of channel gates during action potential

4. 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

5. Summary of equilibrium states and time constants for HH gates

6. Voltage gated channel dynamics
Courtesy W Lytton

7. 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

8. IA is dependent on resting potential

9. Extraction of IA from total IK

10. Simulations with I-A reproduce spike trajectories

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

12. Differential regulation of branches
Debanne et al 1997

13. Calcium indicator & axons

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

15. Molecular identity of M current
Wang et al 1998

16. Antagonists of M current alter spike firing
Wang et al 1998

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

18. Parallel conductance model, Hodgkin and Huxley

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

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

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

22. T channels, Low Threshold Spikes (LTSs), and bursts
Cultured enteric neurons, pair recordings 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: , 1998

23. b
Vm –55 mV
Vm –75 mV

24. Availability of T channels

25. 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

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

27. IT has slow kinetics in nRt cells: ITs

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

29. The H current, slow kinetics
McCormick & Pape, J Physiol :291

30. The H current, activation via hyperpolarization
McCormick & Pape, J Physiol :291

31. The H current, susceptible to neuromodulation
McCormick & Pape, J Physiol :3191

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