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Neuron-Computer Interface in Dynamic-Clamp Experiments.  Models of Neuronal Populations and Visual Cortex. A.V.Chizhov A.F...
Models of single neurons and D ynamic- C lamp <ul><li>- Leaky integrate-and-fire model </li></ul><ul><li>- 2-compartmental...
Leaky Integrate-and-Fire neuron (LIF) E X P E R I M E N T LIF - M O D E L V  is the   membrane potential ;  I   is the inp...
Steady-state firing rate dependence on current   and conductance LIF, no noise LIF with noise
2-compartmental neuron with somatically registered PSC and PSP Figure  Transient activation of somatic and delayed   activ...
PSC and PSP:  single-compartmental neuron model Parameters found to fit  PSC   and PSP : How does the model fit to  simult...
PSC and PSP:   Model of concentrated soma and cylindrical dendrite (“model S-D”)  [W.Rall, 1959] Two boundary problems: A ...
At dendrite : Subtracting  (2),  obtain: Eqs.  (1),(2)  and  (3)  are equivalent to  PSC and PSP:   2- compartmental model...
PSC and PSP:   Fitting experimental PSP and PSC from [Karnup and Stelzer, 1999] Parameters found by fitting, given fixed  ...
V  – somatic potential; V d  –  dendritic potential; I s   – registered on soma current through synapses located  near som...
h [ Покровский,   19 78] φ ≈0 r V(x) V(x+ Δ x ) i m j m C Внутри Снаружи V g K g Na V Na V rest V K Hodgkin-Huxley model A...
Set of experimental data for Hodgkin-Huxley approximations
Approximations for   are taken from [L.Graham, 1999];  I AHP   is from   [N.Kopell et al., 2000] Color noise model for syn...
Control parameters of neuron Property:  Neuron is controlled by two parameters [Pokrovskiy ,   19 78] [Hodgkin, Huxley, 19...
,   The case of many voltage-independent synapses
“ Current clamp” , V(t) is registered “ Voltage clamp” , I(t) is registered Whole-cell patch-clamp: Current- and Voltage-C...
Warning!   The input in current clamp corresponds to negative synaptic conductance!  Current-clamp is here!
<ul><li>For artificial passive leaky channel  s = const </li></ul><ul><li>For  artificial   synaptic channel s ( t )  refl...
“ Current clamp” Conductance clamp (Dynamic clamp): I ( V(t) )= s  ( V(t) - V DC )+u  is injected
Dynamic clamp  for synaptic current [ Sharp AA, O'Neil MB, Abbott LF, Marder E.   Dynamic clamp: computer-generated conduc...
Dynamic clamp  for spontaneous potassium channels Control artificial K-channels
Experiment :  pyramidal cell  of visual cortex in vivo Model   [Graham, 1999] of CA1 pyramidal neuron Dynamic clamp  to st...
Experiment Model  u=7.7 mkA/cm 2 S=0.4 mS/cm 2 u=1.7 mkA/cm 2 S=0.024 mS/cm 2 u=2.7 mkA/cm 2 S=0.06 mS/cm 2 u=4 mkA/cm 2 S...
Divisive effect of shunting inhibition is due to spike threshold sensitivity to slow inactivation of sodium channels
Total Response (all spikes during 500ms-step) Only 1 st  spikes  Only 1 st  interspike intervals
Hippocampal Pyramidal Neuron   In Vitro Dynamic clamp  for voltage-gated current: compensation of  I NaP [Vervaeke K, Hu H...
Effect of “negative conductance” by  I NaP plays a role of negative conductance
Dynamic clamp  for electric couplings between real and modeled neurons Medium  electric  conductance High  electric  condu...
“ Threshold-Clamp”
Dynamic clamp  for synaptic conductance estimations  in-vivo 1s 20 mV 10 nS 5 nS Эксперимент   [Lyle Graham et al.]:   Вну...
« Firing-Clamp »  -  method of synaptic conductance estimation Idea :  a patched neuron is forced to spike with a constant...
Measuring system is a neuron: Firing-Clamp EXPERIMENT
Calibration: Firing-Clamp Cell 16_28_28 Cell 16_29_40 Cell 16_33_14 V T V peak EXPERIMENT
Measurements: Firing-Clamp Cell 16_27_50 Cell 16_27_5 V T V peak EXPERIMENT
<ul><li>Dynamic Clamp   </li></ul><ul><li>is necessary   for measuring firing characteristics of neuron </li></ul><ul><li>...
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Neuron-Computer Interface in Dynamic-Clamp Experiments. Models of Neuronal Populations and Visual Cortex

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AACIMP 2011 Summerschool. Neuroscience Stream. Lecture by Anton Chizhov

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Transcript of "Neuron-Computer Interface in Dynamic-Clamp Experiments. Models of Neuronal Populations and Visual Cortex"

  1. 1. Neuron-Computer Interface in Dynamic-Clamp Experiments. Models of Neuronal Populations and Visual Cortex. A.V.Chizhov A.F.Ioffe Physical-Technical Institute of RAS, St.-Petersburg, Russia <ul><li>Two-compartment neuron model </li></ul><ul><li>Spiking activity as function of current and conductance in-vivo, in-vitro и in-silico </li></ul><ul><li>“ Firing-clamp” algorithm of estimation of synaptic conductances </li></ul><ul><li>Model of statistical ensemble of Hodgkin-Huxley-like neurons - CBRD </li></ul><ul><li>Model of primary visual cortex. Mappings of models of a hypercolumn. </li></ul>Model Experiment
  2. 2. Models of single neurons and D ynamic- C lamp <ul><li>- Leaky integrate-and-fire model </li></ul><ul><li>- 2-compartmental passive neuron model </li></ul><ul><li>- Hodgkin-Huxley neuron model </li></ul><ul><li>- Control parameters of neuron </li></ul><ul><li>- Dynamic - clamp </li></ul><ul><ul><li>Artificial synaptic current </li></ul></ul><ul><ul><li>Artificial voltage-dependent current </li></ul></ul><ul><ul><li>Synaptic conductance estimation </li></ul></ul>
  3. 3. Leaky Integrate-and-Fire neuron (LIF) E X P E R I M E N T LIF - M O D E L V is the membrane potential ; I is the input (synaptic) current; s is the input (synaptic) conductance; C is the membrane capacity ; g L is the membrane conductance ; V rest is the rest potential ; V T is the threshold potential ; V reset is the reset potential .
  4. 4. Steady-state firing rate dependence on current and conductance LIF, no noise LIF with noise
  5. 5. 2-compartmental neuron with somatically registered PSC and PSP Figure Transient activation of somatic and delayed activation of dendritic inhibitory conductances in experiment (solid lines) and in the model (small circles) . A, Experimental configuration. B , Responses to alveus stimulation without (left) and with ( right ) somatic V-clamp. C , In a different cell, responses to dynamic current injection in the dendrite; conductance time course (g) in green, 5-nS peak amplitude , V rev =-85 mV . [F.Pouille, M.Scanziani // Nature , 2004] Parameters of the model:  m = 33 ms ,  = 3.5 , G s = 6 nS in B and 2.4 nS in C <ul><li>Two boundary problems: </li></ul><ul><li>current-clamp to register PSP : </li></ul><ul><li>voltage-clamp to register PSC : </li></ul>Solution: [A.V.Chizhov // Biophysics 2004 ] C V d V d V d V d V s V s I d I s g B A X=0 X=L V d V 0
  6. 6. PSC and PSP: single-compartmental neuron model Parameters found to fit PSC and PSP : How does the model fit to simultaneously recorded PSC and PSP? Parameters found by fitting :
  7. 7. PSC and PSP: Model of concentrated soma and cylindrical dendrite (“model S-D”) [W.Rall, 1959] Two boundary problems: A ) current-clamp to register PSP: B ) voltage-clamp to register PSC, i.e. at the end of dendrite , : Parameters : . at soma , : X=0 X=L X=0 X=L
  8. 8. At dendrite : Subtracting (2), obtain: Eqs. (1),(2) and (3) are equivalent to PSC and PSP: 2- compartmental model B ) Voltage-clamp mode Assume the potential V(X) to be linear, i.e. Model S-D As current through synapse is (1) A ) Current-clamp mode (2) because where is the dendrite conductance Model S-D At soma : (3) At dendrite : V L X=0 X=L V=0 X=0 X=L V L V 0
  9. 9. PSC and PSP: Fitting experimental PSP and PSC from [Karnup and Stelzer, 1999] Parameters found by fitting, given fixed : for 2-compartmental model: for 1-compartmental model: EPSC and EPSP IPSC and IPSP Conclusion. Solution of voltage - and current-clamp boundary problems by 2-compartmental model describes well the PSP-on-PSC dependence.
  10. 10. V – somatic potential; V d – dendritic potential; I s – registered on soma current through synapses located near soma; I d – registered on soma current through synapses located on dendrites;  m – membrane time constant;  – ratio of dendritic to somatic conductances; G s – specific somatic conductance. C V d V d V d V d V s V s I d I s Figure Transient activation of somatic and delayed activation of dendritic inhibitory conductances in experiment (solid lines) and in the model (small circles) . A, Experimental configuration. B , Responses to alveus stimulation without (left) and with ( right ) somatic V-clamp. C , In a different cell, responses to dynamic current injection in the dendrite; conductance time course (g) in green, 5-nS peak amplitude , V rev =-85 mV . Parameters of the model:  m = 33 ms ,  = 3.5 , G s = 6 nS in B and 2.4 nS in C A B [F.Pouille, M.Scanziani (2004) Nature , v. 429(6993):717-23 ] PSC and PSP: Fitting experimental PSP and PSC from [Pouille and Scanziani, 2004]
  11. 11. h [ Покровский, 19 78] φ ≈0 r V(x) V(x+ Δ x ) i m j m C Внутри Снаружи V g K g Na V Na V rest V K Hodgkin-Huxley model Approximations of ionic channels: Parameters:
  12. 12. Set of experimental data for Hodgkin-Huxley approximations
  13. 13. Approximations for are taken from [L.Graham, 1999]; I AHP is from [N.Kopell et al., 2000] Color noise model for synaptic current I S is the Ornstein-Uhlenbeck process : Model of pyramidal neuron Model with noise E X P Е R I М Е N Т
  14. 14. Control parameters of neuron Property: Neuron is controlled by two parameters [Pokrovskiy , 19 78] [Hodgkin, Huxley, 1952] Voltage-gated channels kinetics : EXPERIMENT
  15. 15. , The case of many voltage-independent synapses
  16. 16. “ Current clamp” , V(t) is registered “ Voltage clamp” , I(t) is registered Whole-cell patch-clamp: Current- and Voltage-Clamp modes const
  17. 17. Warning! The input in current clamp corresponds to negative synaptic conductance! Current-clamp is here!
  18. 18. <ul><li>For artificial passive leaky channel s = const </li></ul><ul><li>For artificial synaptic channel s ( t ) reflects the synaptic kinetics </li></ul><ul><li>For voltage-gated channel s ( V ( t ), t ) is described by ODEs </li></ul>Whole-cell patch-clamp: Dynamic-Clamp mode Conductance clamp (Dynamic clamp): V ( t ) is registered , I ( V,t ) = s ( V,t ) ( V(t) - V us ) + u is injected. 30 μ s Acquisition card
  19. 19. “ Current clamp” Conductance clamp (Dynamic clamp): I ( V(t) )= s ( V(t) - V DC )+u is injected
  20. 20. Dynamic clamp for synaptic current [ Sharp AA, O'Neil MB, Abbott LF, Marder E. Dynamic clamp: computer-generated conductances in real neurons. // J. Neurophysiol. 1993 , 69(3):992-5 ]
  21. 21. Dynamic clamp for spontaneous potassium channels Control artificial K-channels
  22. 22. Experiment : pyramidal cell of visual cortex in vivo Model [Graham, 1999] of CA1 pyramidal neuron Dynamic clamp to study firing properties of neuron
  23. 23. Experiment Model u=7.7 mkA/cm 2 S=0.4 mS/cm 2 u=1.7 mkA/cm 2 S=0.024 mS/cm 2 u=2.7 mkA/cm 2 S=0.06 mS/cm 2 u=4 mkA/cm 2 S=0.15 mS/cm 2 Bottom point Top point
  24. 24. Divisive effect of shunting inhibition is due to spike threshold sensitivity to slow inactivation of sodium channels
  25. 25. Total Response (all spikes during 500ms-step) Only 1 st spikes Only 1 st interspike intervals
  26. 26. Hippocampal Pyramidal Neuron In Vitro Dynamic clamp for voltage-gated current: compensation of I NaP [Vervaeke K, Hu H., Graham L.J., Storm J.F. Contrasting effects of the persistent Na+ current on neuronal excitability and spike timing, Neuron, v49, 2006]
  27. 27. Effect of “negative conductance” by I NaP plays a role of negative conductance
  28. 28. Dynamic clamp for electric couplings between real and modeled neurons Medium electric conductance High electric conductance
  29. 29. “ Threshold-Clamp”
  30. 30. Dynamic clamp for synaptic conductance estimations in-vivo 1s 20 mV 10 nS 5 nS Эксперимент [Lyle Graham et al.]: Внутриклеточные измерения patch-clamp в зрительной коре кошки in vivo . Стимул – движущаяся полоска. Preferred direction Null direction
  31. 31. « Firing-Clamp » - method of synaptic conductance estimation Idea : a patched neuron is forced to spike with a constant rate; g E , g I , are estimated from values of subthreshold voltage and spike amplitude . Threshold voltage , V T Peak voltage, V P MODEL 1 ms τ (V)
  32. 32. Measuring system is a neuron: Firing-Clamp EXPERIMENT
  33. 33. Calibration: Firing-Clamp Cell 16_28_28 Cell 16_29_40 Cell 16_33_14 V T V peak EXPERIMENT
  34. 34. Measurements: Firing-Clamp Cell 16_27_50 Cell 16_27_5 V T V peak EXPERIMENT
  35. 35. <ul><li>Dynamic Clamp </li></ul><ul><li>is necessary for measuring firing characteristics of neuron </li></ul><ul><li>helps to create artificial ionic intrinsic or synaptic channels </li></ul><ul><li>is necessary for estimation of input synaptic conductances in-vivo </li></ul>Conclusions
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