LONG-RANGE GABAERGIC PROJECTION NEURONS IN CA1 ORCHESTRATE STATE-DEPENDENT HIPPOCAMPAL-CORTICAL RHYTHMS SUPPORTING MEMORY CONSOLIDATION DURING RAPID EYE MOVEMENT SLEEP

Sleep is crucial for stabilizing experiences into long-lasting memories, a process known as memory consolidation. Rapid eye movement sleep (REMs) is featured by a theta-oscillation (4-10 Hz) dominant cortical brain state, with retrosplenial cortex (RSP) as a primary cortical initiation site. One indicator of successful memory consolidation is increased coherence of theta oscillations between the dorsal hippocampus (DH) and RSP during REMs. Nevertheless, the circuit elements regulating DH-RSP theta coherence and the role of this coherence in REMs during memory consolidation remain untested.
One specialized circuit element that may control coherent DH-RSP activity is the previously described retrosplenial-projecting CA1 GABAergic neuron (CA1-RP), given its axonal projection to ventral RSP (vRSP). To test this hypothesis, we combined in vivo antidromic phototagging with tetrode recordings to monitor CA1-RP neuron activity and EEG/EMG recordings to determine sleep states. We found that CA1-RP neurons are highly active during REMs. Intersectional viral tracing and in vitro circuit mapping with optogenetics revealed that CA1-RP neurons primarily receive inputs from CA3 and the medial septum, regions for theta oscillation generation. CA1-RP neurons target pyramidal cells and interneurons in DH and vRSP, suggesting their ability to coordinate DH-vRSP network activity. Optogenetic inhibition of CA1-RP neurons during post-learning REMs reduced CA1-vRSP theta coherence and impaired novel object place recognition performance, indicating their necessity for REMs-dependent memory consolidation. These data indicate that CA1-RP neurons serve as a powerful coordinator of hippocampal-cortical rhythm during REMs, which is critical for memory consolidation.