Frequency dependence of CA3 spike phase response arising from h-current properties

Abstract

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 (Ih), 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 Ih 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 Ih 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 Ih 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.

Comparison of three gamma oscillations in the mouse entorhinal–hippocampal system

“…As the duration of the inhibitory postsynaptic current (IPSC) is thought to determine the pace of the rhythm (Fisahn et al, 1998;Atallah & Scanziani, 2009), it is possible that the generators involve different interneurons which produce IPSCs of different durations thus resulting in gamma oscillations of different frequencies. An alternative explanation is that pyramidal neurons in CA3 have a longer time constant than those in CA1 (Borel et al, 2013). Moreover, pyramidal neurons in CA3 are highly recurrently connected (Lorente de N o, 1934) whereas the principal neurons in CA1 and in layer II of the mEC are not (Pastoll et al, 2013).…”

Dementia-related Bri2 BRICHOS is a versatile molecular chaperone that efficiently inhibits Aβ42 toxicity in Drosophila

“…The EC has been shown to be vital for spatial navigation (78) and SC inputs from CA3 to CA1 have been shown to be important for memory consolidation (79). Some regions of the hippocampus have been shown to be intrinsically oscillogenic, such as the CA3 region (44,59,(80)(81)(82). Furthermore, a recent study has shown that CA1 is also capable of generating intrinsic gamma oscillation in response to a theta input in addition to inheriting activity from the projections received from CA3 and EC (83).…”

Phase-resetting as a tool of information transmission

“…A different proposed phase code suggests that the biphasic ability of excitatory synaptic inputs to jitter the spike timing of CA1 and CA3 hippocampal pyramidal neurons phase-locked by a sinusoidal theta oscillation is useful for encoding memories [58]. The biphasic response is due to the unconventional protocol; when CA1 neurons are biased in a pacemaker regime they exhibit a monophasic PRC [11].…”