Presented by Suganya Karunakaran 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, (4):973–
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
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
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
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
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
Computational Consequence May fundamentally chance dendrite integration properties Reduced membrane time constant – change in Temporal Processing High conductance State Decrease in integration time constant Increase in spike output variability
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
Model
Model ctnd.
Parameters
Non adapting Cells The ability of a high conductance state to increase ISI variability depends on the subtype of pyramidal cell. High conductance state – Leakier membranes Faster decay rates for synaptic inputs Increases ISI variability
Model 3 Dimensions V h (I Na inactivation ) n (I KCa activation) Single pulse-excited spike produces a larger ADP under control conditions than with added leak conductance
Single pulse Excitation Matlab Model- Reproduced Result
Decrease in CV
Phase Plane Analysis - Control Blue – Stable fixed point Black – Unstable fixed point Reproduced Result
Phase Plane Analysis – with leak
Phase Plane Analysis
Bifurcation Analysis
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