Active and Passive Membrane Properties and Intrinsic Kinetics Shape Synaptic Inhibition in Hippocampal CA1 Pyramidal Neurons

The impact of synaptic inhibition depends on the passive and active properties of the neuronal membrane as well as on the characteristics of the underlying synaptic conductances. Here, we evaluated the contributions of these different factors to the IPSPs produced by two kinetically and anatomically distinct inhibitory synapses onto hippocampal CA1 pyramidal neurons: somatic GABA(A,fast) and dendritic GABA(A,slow). Using combined current-clamp and voltage-clamp recordings from neurons in hippocampal brain slices, we found that despite pronounced differences in kinetics and only weak voltage dependence of the underlying synaptic conductances, there were much smaller differences in duration but strong voltage dependence of IPSPs arising from somatic and dendritic synapses. Pharmacologic tests and compartmental modeling showed that these effects were produced by the hyperpolarization-activated cation current, I(H), which accelerated IPSP decay over a broad range of membrane potentials and reduced IPSP amplitudes at hyperpolarized potentials, and the persistent sodium current, I(NaP), which prolonged and amplified IPSPs at depolarized subthreshold potentials. The relative magnitudes of their influences depended on the kinetics of the underlying synaptic conductances: the effect on duration was greater for GABA(A,fast) and on amplitude was greater for GABA(A,slow). Passive and active factors thus influence the impact of synaptic inhibition in a location- and voltage-dependent manner.