Kavli Affiliate: Solomon Snyder
| Authors: Robin Roychaudhuri, Hasti Atashi and Solomon Snyder
| Summary:
The hippocampal CA3 subregion is a densely connected recurrent circuit that supports memory consolidation and retrieval by generating and storing sequential neuronal activity patterns that reflect recent experience. The encoding of precise temporal firing patterns in CA3 ensembles during awake-behavior is supported by phase precession, in which spike timing shifts with reference to local theta oscillations that are prominent in the hippocampus during active learning. Although phase precession is thought to be critical for generating sequential activity during memory encoding, the circuit mechanisms that support this computation across hippocampal subregions are unknown. By assessing CA3 network activity in the absence of each of its theta modulated excitatory inputs, the dentate gyrus (DG) and the medial entorhinal cortex (MEC), we show necessary and unique contributions of each region to phase precession. DG inputs to the CA3 circuit are essential for organizing the temporal order of neuronal firing by promoting the expression of prospective “look-ahead” sequential spiking during theta states. In contrast, MEC inputs to CA3 modulate the gain of excitation and increase the precision of phase precession, but are not necessary for generating the temporally ordered activity of CA3 neurons. We propose a simple computational model that accounts for the empirical findings by proposing different effects of each of the feedforward pathways on inhibitory subnetworks. DG inputs affect the phase and MEC inputs affect the amplitude of the inhibitory theta signal. Our results thus describe circuit mechanisms that are required for the generation of sequence coding in the CA3 recurrent circuit.