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Gava, G. P.

Publications and source records attributed to Gava, G. P..

4 recordsLinked to original sources

Hippocampal Ripple Diversity organises Neuronal Reactivation Dynamics in the Offline Brain

SO_SCPLOWUMMARYC_SCPLOWHippocampal ripples are highly synchronized neuronal population patterns reactivating past waking experiences in the offline brain. Whether the level, structure, and content of ripple-nested activity are consistent across consecutive events or are tuned in each event remains unclear. By profiling individual ripples using laminar currents in the mouse hippocampus during sleep/rest, we identified Radsink and LMsink ripples featuring current sinks in stratum radiatum versus stratum lacunosum-moleculare, respectively. These two ripple profiles recruit neurons differently. Radsink ripples integrate recent motifs of waking coactivity, combining superficial and deep CA1 principal cells into denser, higher-dimensional patterns that undergo hour-long stable reactivation. In contrast, LMsink ripples contain core motifs of prior coactivity, engaging deep cells into sparser, lower-dimensional patterns that undergo a reactivation drift, gradually updating their pre-structured content for recent wakefulness. We propose that ripple-by-ripple diversity instantiates parallel reactivation channels for stable integration of recent wakefulness and flexible updating of prior internal representations.

neuroscience↗

Offline hippocampal reactivation during dentate spikes supports flexible memory

Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the Cornu Ammonis (CA) region, and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events supporting this offline process. SWRs have been studied extensively but the contribution of DSs remains unclear. By combining triple-(DG-CA3-CA1) ensemble recordings and closed-loop optogenetics in mice we show that, like SWRs, DSs synchronize spiking across DG and CA principal cells to reactivate population-level patterns of neuronal coactivity expressed during prior waking experience. Notably, the population coactivity structure in DSs is more diverse and higher-dimensional than that seen during SWRs. Importantly, suppressing DG granule cell spiking selectively during DSs impairs subsequent flexible memory performance in a multi-object recognition task and associated hippocampal patterns of neuronal coactivity. We conclude that DSs constitute a second offline network event central to hippocampal population dynamics serving memory-guided behavior.

neuroscience↗

Organizing the coactivity structure of the hippocampus from robust to flexible memory

New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons of the superficial CA1 pyramidale sublayer to whole population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to successfully meet memory demands.

neuroscience↗

Place cells in head-fixed mice navigating a floating real-world environment

The hippocampal place cell system in rodents has provided a major paradigm for the scientific investigation of memory function and dysfunction. Place cells have been observed in area CA1 of the hippocampus of both freely moving animals, and of head-fixed animals navigating in virtual reality environments. However, spatial coding in virtual reality preparations has been observed to be impaired. Here we show that the use of a real-world environment system for head-fixed mice, consisting of a track floating on air, provides some advantages over virtual reality systems for the study of spatial memory. We imaged the hippocampus of head-fixed mice injected with the genetically encoded calcium indicator GCaMP6s while they navigated circularly constrained or open environments on the floating platform. We observed consistent place tuning in a substantial fraction of cells with place fields remapping when animals entered a different environment. When animals re-entered the same environment, place fields typically remapped over a time period of multiple days, faster than in freely moving preparations, but comparable with virtual reality. Spatial information rates were within the range observed in freely moving mice. Manifold analysis indicated that spatial information could be extracted from a low-dimensional subspace of the neural population dynamics. This is the first demonstration of place cells in head-fixed mice navigating on an air-lifted real-world platform, validating its use for the study of brain circuits involved in memory and affected by neurodegenerative disorders.

neuroscience↗