Opposing Effects of Intrinsic Conductance and Correlated Synaptic Input on V-Fluctuations during Network Activity.

Neurons often receive massive concurrent bombardment of synaptic inhibition and excitation during functional network activity. This increases membrane conductance and causes fluctuations in membrane potential (V(m)) and spike timing. The conductance increase is commonly attributed to synaptic conductance, but also includes the intrinsic conductances recruited during network activity. These two sources of conductance have contrasting dynamic properties at sub-threshold membrane potentials. Synaptic transmitter gated conductance changes abruptly and briefly with each presynaptic action potential. If the spikes arrive at random times the changes in synaptic conductance are therefore stochastic and rapid during intense network activity. In comparison, sub-threshold intrinsic conductances vary smoothly in time. In the present study this discrepancy is investigated using two conductance-based models: a (1) compartment model and a (2) compartment with realistic slow intrinsic conductances. We examine the effects of varying the relative contributions of non-fluctuating intrinsic conductance with fluctuating concurrent inhibitory and excitatory synaptic conductance. For given levels of correlation in the synaptic input we find that the magnitude of the membrane fluctuations uniquely determines the relative contribution of synaptic and intrinsic conductance. We also quantify how V(m)-fluctuations vary with synaptic correlations for fixed ratios of synaptic and intrinsic conductance. Interestingly, the levels of V(m) -fluctuations and conductance observed experimentally during functional network activity leave little room for intrinsic conductance to contribute. Even without intrinsic conductances the variance in V(m) -fluctuations can only be explained by a high degree of correlated firing among presynaptic neurons.