Control of output gain in CA1 pyramidal cells using somatic shunting inhibition

Abstract

Event Abstract Back to Event Control of output gain in CA1 pyramidal cells using somatic shunting inhibition Introduction: Gain modulation refers to a change in the scaling between the input and output of a system. In neurobiology, it has been shown that gain control is a fundamental computation performed by numerous brain regions (1, 2). At the cellular level, gain control can manifests itself as a change in the slope of the spike frequency-current (F-I) relationship. Results from cortical pyramidal and cerebellar granule cells have shown that, unlike the subthreshold current-voltage (I-V) relationship, an increase in membrane conductance does not decrease the slope of the F-I relationship (3-7). Several studies, however, have shown that gain control can be implemented using membrane voltage fluctuations (3, 6). An assumption in investigating the relationship between gain and conductance has been that changes in membrane leak conductance do not alter the intrinsic firing dynamics of the neuron outside of the expected changes in membrane time constant and input resistance. Recent data, however, has shown that increased somatic conductance can profoundly alter intrinsic properties (8, 9). In the current study, we investigated the ability for different levels of constant leak conductance applied at the soma of CA1 pyramidal cells to modulate the gain of the F-I relationship without noise. Methods: Patch-clamp recordings from hippocampal CA1 pyramidal cells were implemented using standard in vitro slice electrophysiology. A leak conductance with a reversal of -65 mV was introduced at the soma using dynamic clamp. The effects of leak conductance on the spike output gain of CA1 pyramidal cells were quantified by measuring the steady-state F-I relationship in the presence of different levels of added leak conductance (5, 10 and 15 nS). Results and Conclusions: We find that increased conductance has a strong divisive effect on the steady-state F-I relationship of CA1 pyramidal cells. The reduction in gain with increased leak conductance is associated with a more depolarized operating voltage range and increase in spike threshold. The more depolarized operating voltage results in a progressive increase in the magnitude of spike frequency adaptation through increased Na+ conductance inactivation. It has been established that spike frequency adaptation has a divisive effect on the F-I relationship (10, 11). Hence, the increase in spike frequency adaptation with leak conductance provides a mechanism for gain control.