Presented by Suganya Karunakaran

1. Reduction of Spike Afterdepolarization by Increased Leak Conductance Alters Interspike Interval Variability Fernando R. Fernandez and John A.White The Journal of Neuroscience, January 28, 2009 • 29(4):973–986 • 973 Presented by Suganya Karunakaran

2. Spike Afterdepolarization • Membrane potential depolarization that follows an action potential • May occur before (early) or after (delayed) full repolarization • Common in cardiac muscles • Sometimes occurs in tissues not normally excitable

3. Leak Conductance • Leak conductance is generated by membrane damage surrounding an electrode and an increase in K+ permeability evoked by cytosolic elevations of Sodium and Calcium

4. Interspike Interval Variability • Inter-spike Interval • Variability of neuronal spike train – important indicator of the type of processing a neuron performs on its synaptic inputs • Simplest measure – Coefficient of Variability CV = standard deviation of ISI distribution/mean ISI • Refractory period lowers the CV at high firing rates when it tends to force regularity in the ISI duration

5. High-Conductance state • State of neurons in an active network • Total synaptic conductance received by the neuron (over a period of time) is larger than its resting conductance • Found in thalamocortical system especially cerebral cortex • Neurons can integrate differently in this state • Can be reproduced by dynamic-clamp experiments

6. Computational Consequence • Neuronal responses in high-conductance states are probabilistic because of the high variability of responses due to the presence of fluctuating background activity • Change the response properties of neurons Red- deterministic neuron Green- probabilistic neuron

7. Computational Consequence • May fundamentally chance dendrite integration properties • Reduced membrane time constant – change in Temporal Processing

8. Previous Results • Effects of background synaptic conductance activity on ISI variability depends on neuron type For a conductance based stimulus, • In pyramidal cells lacking spike frequency adaptation, variability increased • In pyramidal cells displaying spike frequency adaptation, variability decreased (τ differs between two subtypes) • Leak – bifurcation parameter • Reduces afterdepolarization (ADP) • Decrease the gain of frequency-current relationship

9. Model

10. Model ctnd.

11. Parameters

12. Non adapting Cells • The ability of a high conductance state to increase ISI variability depends on the subtype of pyramidal cell.

13. Model • 3 Dimensions • V • h (INa inactivation ) • n (IKCa activation) • Single pulse-excited spike produces a larger ADP under control conditions than with added leak conductance

14. Single pulse Excitation Matlab Model- Reproduced Result

15. Decrease in CV

16. Phase Plane Analysis - Control Reproduced Result Blue – Stable fixed point Black – Unstable fixed point

17. Phase Plane Analysis – with leak Reproduced Result

18. Phase Plane Analysis

19. Bifurcation Analysis

20. Conclusion • The decrease in CV of the model with added leak conductance can be explained as a consequence of a lower gain in the F-I relationship resulting from the changes in the ADP and bifurcation in the fast subsystem of the model

21. Thank You Questions?