Persistent Na and M-type K currents opposingly control spike gain in CA3 pyramidal cells.

Neural firing response gain and spike threshold are critical intrinsic cell properties that define input-output relations in neurons. Alterations of these cellular properties in hippocampal pyramidal cells (PCs) may strongly influence network dynamics in health and disease. Here we investigated how specific voltage-gated conductance affect these properties in adult rat CA3 pyramidal cells (PCs) in hippocampal slices under near-physiological conditions. We examined currents activated at near-threshold potential - persistent sodium current (I), T-type Ca current (I), M-type K current (I), SK Ca - dependent current (I) and h-type cationic current (I) through pharmacological modulation and analysis of resulting changes. CA3 PCs showed high heterogeneity in firing response gain, likely reflecting individual variations in active conductance at rest. Blocking I by riluzole decreased firing response gain, an effect associated with a reduction in the depolarizing shift (DS) underlying evoked spike trains. Conversely, blocking I with XE991 markedly increased firing response gain, decreased the DS, increased input resistance, and lowered spike threshold. Enhancing I by retigabine produced opposite effects. Blocking I with apamin moderately augmented firing response gain, while blocking I and I exerted no effect on discharge. Our findings identify I and I as key determinants of spike response gain and threshold of CA3 PCs, suggesting that modulators of these currents may effectively modify neuronal input-output relations in both normal and pathological states of hippocampal hypo- or hyperexcitability.