Transcript Increased leak conductance alters ISI variability.

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
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
(INa inactivation )
 n (IKCa 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
Reproduced Result
Blue – Stable fixed point
Black – Unstable fixed point
Phase Plane Analysis – with leak
Reproduced Result
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