Control of recollection by slow gamma dominating mid-frequency gamma in hippocampus CA1

Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome, but behavior is a proxy for unknown neural events that define cognitive variables like recollection. We identified an electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1 (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30–50 Hz) dominates mid-frequency gamma (MG) (70–90 Hz) oscillations 2–3 s before successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom) decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom, putative pyramidal cell ensembles represent distant locations; during place avoidance, these are avoided places. During shock relocation, WT ensembles represent distant locations near the currently correct shock zone, but Fmr1-null ensembles represent the formerly correct zone. These findings indicate that recollection occurs when CA1 SG dominates MG and that accurate recollection of inappropriate memories explains Fmr1-null cognitive inflexibility.Author summary: Behavior is often used as proxy to study memory and cognitive deficits in animals like Fmr1-KO mice that model Fragile X Syndrome, the most prevalent single-gene cause of intellectual disability and autism. However, it is unclear what neural events define cognitive variables like recollection of memory and cognitive inflexibility. We identified a signature of recollection in the local field potentials of mouse dorsal CA1 hippocampus. When mice on a rotating platform avoided an invisible, fixed shock zone, slow gamma (30–50 Hz) oscillations dominated mid-frequency gamma (70–90 Hz) oscillations (SGdom) 2–3 s before mice successfully avoided the shock zone. Wild-type but not Fmr1-KO mice adapt to relocating the shock zone; concurrently, SGdom decreases in wild-type but not in cognitively inflexible Fmr1-KO mice. During SGdom, principal cell ensembles represent distant locations; during place avoidance, these are avoided places in the shock zone vicinity. During shock relocation, wild-type ensembles encode distant locations near the currently correct shock zone, but Fmr1-KO ensembles manifest representational inflexibility, encoding the formerly correct zone. These findings suggest evidence for competition amongst CA1 inputs for CA1 information-processing modes and indicate that recollection occurs when CA1 slow gamma dominates mid-frequency gamma and that accurate recollection of inappropriate memories explains Fmr1-KO cognitive inflexibility.