We used the psychotomimetic phencyclidine (PCP) to investigate the relationships among cognitive behavior, coordinated neural network function, and information processing within the hippocampus place cell system. We report in rats that PCP (5 mg/kg, i.p.) impairs a well learned, hippocampus-dependent place avoidance behavior in rats that requires cognitive control even when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium-freguency gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive impairment caused by systemic PCP administration. PCP discoordinates theta-modulated medium-frequency and slow gamma oscillations in CA1 LFPs such that medium-frequency gamma oscillations become more thetaorganized than slow gamma oscillations. CA1 place cell firing fields are preserved under PCP, but the drug discoordinates the subsecond temporal organization of discharge among place cells. This discoordination causes place cell ensemble representations of a familiar space to cease resembling pre-PCP representations despite preserved place fields. These findings point to the cognitive impairments caused by PCP arising from neural discoordination. PCP disrupts the timing of discharge with respect to the subsecond timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from local inhibitory synaptic activity, these findings point to excitationinhibition discoordination as the root of PCP-induced cognitive impairment.

Hippocampus CA1 place cells express a spatial neural code by discharging action potentials in cell-specific locations (′place fields′), but their discharge timing is also coordinated by multiple mechanisms, suggesting an alternative ′ensemble cofiring′ neural code, potentially distinct from place fields. We compare the importance of these distinct information representation schemes for encoding environments. Using miniature microscopes, we recorded the ensemble activity of mouse CA1 principal neurons expressing GCaMP6f across a multi-week experience of two distinct environments. We find that both place fields and ensemble coactivity relationships are similarly reliable within environments and distinctive between environments. Decoding the environment from cell-pair coactivity relationships is effective and improves after removing cell-specific place tuning. Ensemble decoding relies most crucially on anti-coactive cell pairs distributed across CA1 and is independent of place cell firing fields. We conclude that ensemble cofiring relationships constitute an advantageous neural code for environmental space, independent of place fields.

Mouse hippocampus CA1 place-cell discharge typically encodes current location but during slow gamma dominance (SGdom), when slow gamma oscillations (30-60 Hz) dominate mid-frequency gamma oscillations (60-90 Hz) in CA1 local field potentials, CA1 discharge switches to represent distant recollected locations. We now report that dentate spike type 2 (DSM) events initiated by MECII→DG inputs promote SGdom and change CA1 discharge, whereas type 1 (DSL) events initiated by LECII→DG inputs do not. Just before SGdom, LECII-originating slow gamma oscillations in dentate gyrus and CA3-originating slow gamma oscillations in CA1 become optimally phase and frequency synchronized at the DSM peak when the firing rates of DG, CA3, and CA1 principal cells increase to promote DG→CA3→CA1 cofiring optimized for the 5-10 ms DG-to-CA1 neuro-transmission that coincides with SGdom. Several properties and consequences of DSM demonstrate extrahippocampal control of SGdom, identifying a cortico-hippocampal mechanism that switches between memory-related hippocampal information processing modes.

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