The phase of firing of hippocampal neurons during theta oscillations encodes spatial information. Moreover, the spike phase response to synaptic inputs in individual cells depends on the expression of the hyperpolarization-activated mixed cation current (I h ), which differs between CA3 and CA1 pyramidal neurons. Here, we compared the phase response of these two cell types, as well as their intrinsic membrane properties. We found that both CA3 and CA1 pyramidal neurons show a voltage sag in response to negative current steps but that this voltage sag is significantly smaller in CA3 cells. Moreover, CA3 pyramidal neurons have less prominent resonance properties compared to CA1 pyramidal neurons. This is consistent with differential expression of I h by the two cell types. Despite their distinct intrinsic membrane properties, both CA3 and CA1 pyramidal neurons displayed bidirectional spike phase control by excitatory conductance inputs during theta oscillations. In particular, excitatory inputs delivered at the descending phase of a dynamic clamp-induced membrane potential oscillation delayed the subsequent spike by nearly 50 mrad. The effect was shown to be mediated by I h and was counteracted by increasing inhibitory conductance driving the membrane potential oscillation. Using our experimental data to feed a computational model, we showed that differences in I h between CA3 and CA1 pyramidal neurons could predict frequency-dependent differences in phase response properties between these cell types. We confirmed experimentally such frequency-dependent spike phase control in CA3 neurons. Therefore, a decrease in theta frequency, which is observed in intact animals during novelty, might switch the CA3 spike phase response from unidirectional to bidirectional and thereby promote encoding of the new context.
Keywords: CA1; CA3; Ih; hippocampus; phase response; resonance; theta oscillation.