Week 2 – part 5: Detailed Biophysical Models 2.1 Biophysics of neurons Neuronal Dynamics: - Overview 2.2 Reversal potential Computational Neuroscience - Nernst equation of Single Neurons 2.3 Hodgin-Huxley Model 2.4 Threshold in the Week 2 – Biophysical modeling: Hodgkin-Huxley Model The Hodgkin-Huxley model - where is the firing threshold? Wulfram Gerstner 2.5. Detailed biophysical models - the zoo of ion channels EPFL, Lausanne, Switzerland Neuronal Dynamics – 2.5 Biophysical models inside Ka Na outside Ion channels Ion pump α β Neuronal Dynamics – 2.5 Ion channels Na+ K+ Steps: Different number Ca2+ of channels Ions/proteins Na+ channel from rat heart (Patlak and Ortiz 1985) A traces from a patch containing several channels. Bottom: average gives current time course. B. Opening times of single channel events Neuronal Dynamics – 2.5 Biophysical models inside Ka There are about 200 identified ion channels Na outside Ion channels Ion pump http://channelpedia.epfl.ch/ How can we know α which ones are present β in a given neuron? Ion Channels investigated in the study of! α Toledo-Rodriguez, …, Markram (2004) Voltage Activated K+ Channels! Kv α β Kv1 Kv2 Kv3 Kv4 Kv5 Kv6 Kv8 Kv9 β Kvβ KChIP + + Kvβ1 Kvβ2 Kvβ3 Kv1.1 Kv1.2 Kv1.3 Kv1.4 Kv1.5 Kv1.6 Kv2.1 Kv2.2 Kv3.1 Kv3.2 Kv3.3 Kv3.4 Kv4.1 Kv4.2 Kv4.3 KChIP1 KChIP2 KChIP3 ! ! ! ! ! ! ! ! ! ! ! ! CB PV CR NPY VIP Dyn SP CRH SOM CCK pENK CGRP I C g gl Na gKv1 g schematic mRNA! Kv3 Expression profile! Model of a hypothetical neuron I inside Ka C g gl Na gKv1 gKv3 Na outside Ion channels Ion pump stimulus I Na IK Ileak du C = −g m3h(u − E ) − g n4 (u − E ) − g n2 (u − E ) − g (u − E ) + I(t) dt Na Na Kv1 Kv1 K Kv3 Kv3 K l l How many parameters per channel? nnu() dndhdm1 h −m10,1h−−(um) (u) dn nnu10,3− () Erisir et al, 1999 ===−−− 0 0 3 =− dt() u Hodgkin and Huxley, 1952 dtdt τ hτ(τun,1m) (u) dtτ n,3 () u Model of a hypothetical neuron Spike I(t) I Subthreshold C g gl Na gKv1 gKv3 Detailed model, based on ion channels Model of a hypothetical neuron (type I) Current pulse Biophysical model, based constant on ion channels current I - Delayed AP initiation C g gl - Smooth f-I curve Na gKv1 g Kv3 type I neuron Neuronal Dynamics – 2.5 Adaptation Functional roles of channels? - Example: adaptation u I Neuronal Dynamics – 2.5 Adaptation: IM -current M current: IgmuEMM=()− K - Potassium current - Kv7 subunits - slow time constant Yamada et al., 1989 IM current is one of many potential sources of adaptation Neuronal Dynamics – 2.5 Adaptation – INaP current current: IgmhuENaP= NaP()− Na - persistent sodium current - fast activation time constant - slow inactivation ( ~ 1s) INaP current - increases firing threshold Aracri et al., 2006 - source of adaptation Neuronal Dynamics – 2.5 Biophysical models inside Ka Na outside Ion channels Ion pump β Hodgkin-Huxley model provides flexible framework Hodgkin&Huxley (1952) Nobel Prize 1963 Exercise – 2. 5. Hodgkin-Huxley model – gating dynamics A) Often the gating dynamics is formulated as dm =αβ()(1um−− ) () um dm mmu− 0 () dt mm =− dtτ m () u Calculate mu0 () andτ m () u 1 B) Assume a form αβ()uu== () mm 1exp[( −− uab + )/] How are a and b related to γθ and in the equations dm mmu− () =− 0 dtτ m () u mu0 ()=+ 0.5{1tanh[(γθ u − )] C ) What is the time constant τ m () u ? Neuronal Dynamics – References and Suggested Reading - Hodgkin, A. L. and Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol, 117(4):500-544. - Ranjan, R.,et al. (2011). Channelpedia: an integrative and interactive database for ion channels. Front Neuroinform, 5:36. - Toledo-Rodriguez, M., Blumenfeld, B., Wu, C., Luo, J., Attali, B., Goodman, P., and Markram, H. (2004). Correlation maps allow neuronal electrical properties to be predicted from single- cell gene expression profiles in rat neocortex. Cerebral Cortex, 14:1310-1327. - Yamada, W. M., Koch, C., and Adams, P. R. (1989). Multiple channels and calcium dynamics. In Koch, C. and Segev, I., editors, Methods in neuronal modeling, MIT Press. - Aracri, P., et al. (2006). Layer-specic properties of the persistent sodium current in sensorimotor cortex. Journal of Neurophysiol., 95(6):3460-3468. Reading: W. Gerstner, W.M. Kistler, R. Naud and L. Paninski, Neuronal Dynamics: from single neurons to networks and models of cognition. Chapter 2: The Hodgkin-Huxley Model, Cambridge Univ. Press, 2014 OR W. Gerstner and W. M. Kistler, Spiking Neuron Models, Chapter 2, Cambridge, 2002 .