Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations dynamically coupled with hippocampal rhythms across brain states.

The granular retrosplenial cortex (gRSC) exhibits high-frequency oscillations (HFOs; ∼150 Hz), which can be driven by a hippocampus-subiculum pathway. How the cellular-synaptic and laminar organization of gRSC facilitates HFOs is unknown. Here, we probe gRSC HFO generation and coupling with hippocampal rhythms using focal optogenetics and silicon-probe recordings in behaving mice. ChR2-mediated excitation of CaMKII-expressing cells in L2/3 or L5 induces HFOs, but spontaneous HFOs are found only in L2/3, where HFO power is highest. HFOs couple to CA1 sharp wave-ripples (SPW-Rs) during rest and the descending phase of theta. gRSC HFO current sources and sinks are the same for events during both SPW-Rs and theta oscillations. Independent component analysis shows that high gamma (50-100 Hz) in CA1 stratum lacunosum moleculare is comodulated with HFO power. HFOs may thus facilitate interregional communication of a multisynaptic loop between the gRSC, hippocampus, and medial entorhinal cortex during distinct brain and behavioral states.

Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations coupled with hippocampal theta and gamma in online states or sharp-wave ripples in offline states.

Neuronal oscillations support information transfer by temporally aligning the activity of anatomically distributed 'writer' and 'reader' cell assemblies. High-frequency oscillations (HFOs) such as hippocampal CA1 sharp-wave ripples (SWRs; 100-250 Hz) are sufficiently fast to initiate synaptic plasticity between assemblies and are required for memory consolidation. HFOs are observed in parietal and midline cortices including granular retrosplenial cortex (gRSC). In 'offline' brain states (e.g. quiet wakefulness) gRSC HFOs co-occur with CA1 SWRs, while in 'online' states (e.g. ambulation) HFOs persist with the emergence of theta oscillations. The mechanisms of gRSC HFO oscillations, specifically whether the gRSC can intrinsically generate HFOs, and which layers support HFOs across states, remain unclear. We addressed these issues in behaving mice using optogenetic excitation in individual layers of the gRSC and high density silicon-probe recordings across gRSC layers and hippocampus CA1. Optogenetically induced HFOs (iHFOs) could be elicited by depolarizing excitatory neurons with 100 ms half-sine wave pulses in layer 2/3 (L2/3) or layer 5 (L5) though L5 iHFOs were of lower power than in L2/3. Critically, spontaneous HFOs were only observed in L2/3 and never in L5. Intra-laminar monosynaptic connectivity between excitatory and inhibitory neurons was similar across layers, suggesting other factors restrict HFOs to L2/3. To compare HFOs in online versus offline states we analyzed, separately, HFOs that did or did not co-occur with CA1 SWRs. Using current-source density analysis we found uniform synaptic inputs to L2/3 during all gRSC HFOs, suggesting layer-specific inputs may dictate the localization of HFOs to L2/3. HFOs occurring without SWRs were aligned with the descending phase of both gRSC and CA1 theta oscillations and were coherent with CA1 high frequency gamma oscillations (50-80 Hz). These results demonstrate that gRSC can internally generate HFOs without rhythmic inputs and that HFOs occur exclusively in L2/3, coupled to distinct hippocampal oscillations in online versus offline states.

Hippocampal sharp wave-ripple dynamics in NREM sleep encode motivation for anticipated physical activity.

Physical activity is an integral part of every mammal's daily life, and as a driver of Darwinian fitness, required coordinated evolution of the body and brain. The decision to engage in physical activity is driven either by survival needs or by motivation for the rewarding qualities of physical activity itself. Rodents exhibit innate and learned motivation for voluntary wheel running, and over time run longer and farther, reflecting increased incentive salience and motivation for this consummatory behavior. Dynamic coordination of neural and somatic physiology are necessary to ensure the ability to perform behaviors that are motivationally variable. Hippocampal sharp wave-ripples (SWRs) have evolved both cognitive and metabolic functions, which in modern mammals may facilitate body-brain coordination. To determine if SWRs encode aspects of exercise motivation we monitored hippocampal CA1 SWRs and running behaviors in adult mice, while manipulating the incentive salience of the running experience. During non-REM (NREM) sleep, the duration of SWRs before (but not after) running positively correlated with future running duration, and larger pyramidal cell assemblies were activated in longer SWRs, suggesting that the CA1 network encodes exercise motivation at the level of neuronal spiking dynamics. Inter-Ripple-intervals (IRI) before but not after running were negatively correlated with running duration, reflecting more SWR bursting, which increases with learning. In contrast, SWR rates before and after running were positively correlated with running duration, potentially reflecting a tuning of metabolic demand for that day's anticipated and actual energy expenditure rather than motivation. These results suggest a novel role for CA1 in exercise behaviors and specifically that cell assembly activity during SWRs encodes motivation for anticipated physical activity. SIGNIFICANCE STATEMENT: Darwinian fitness is increased by body-brain coordination through internally generated motivation, though neural substrates are poorly understood. Specific hippocampal rhythms (i.e., CA1 SWRs), which have a well-established role in reward learning, action planning and memory consolidation, have also been shown to modulate systemic [glucose]. Using a mouse model of voluntary physical activity that requires body-brain coordination, we monitored SWR dynamics when animals were highly motivated and anticipated rewarding exercise (i.e., when body-brain coordination is of heightened importance). We found that during non-REM sleep before exercise, SWR dynamics (which reflect cognitive and metabolic functions) were correlated with future time spent exercising. This suggests that SWRs support cognitive and metabolic facets that motivate behavior by coordinating the body and brain.