Inhibitory dynamics during sharp wave-ripples in the hippocampus

Sharp wave-ripples (SPW-Rs) are short, high-frequency electrographic events critically involved in learning and memory. In the hippocampus, where SPW-Rs are generated, distinct types of interneurons show diverse activity dynamics during these oscillations. One characteristic behaviour is displayed by TORO cells we recently described, such GABAergic neurons that show particularly robust spiking activity during SPW-Rs but reduced firing during theta activity. The disinhibitory nature of TORO cells raises the question of whether interneurons with opposite behavior also exists. In this study, using high-throughput two-photon imaging, we scanned through interneuronal activity in all layers of the CA1 region. We found that interneurons that show reduced activity during SPW-Rs but increased activation during running-associated theta periods are particularly abundant in proximity to the radiatum/lacunosum-moleculare border. To further characterize these cells we performed two-photon imaging and juxtacellular recordings in awake mice and identified a GABAergic cell population that belongs to the cholecystokinin (CCK)-expressing subfamily of interneurons and targets layer-specific dendritic compartments of CA1 pyramidal cells. In addition, we find that such CCK-expressing interneurons receive strong inhibition from muscarinic type 2-expressing neurons, a cell population that includes TORO cells. Our findings outline a functional circuit element ideally positioned to permit CA3 inputs to feed onto CA1 dendrites via Schaffer collaterals during SPW-Rs and thus to play an important role in SPW-R mediated learning and memory mechanisms.