PFC regulates dorsal hippocampus (dHPC) via long-range GABAergic (LRG) projections
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LRG projections augment feedforward inhibition by targeting VIP interneurons in CA1
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PFC–dHPC LRG projections enhance object-related spatial encoding in CA1
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PFC–dHPC LRG projections promote object exploration and CA1-PFC gamma synchrony
Summary
Prefrontal cortex (PFC) is postulated to exert “top-down control” on information processing throughout the brain to promote specific behaviors. However, pathways mediating top-down control remain poorly understood. In particular, knowledge about direct prefrontal connections that might facilitate top-down control of hippocampal information processing remains sparse. Here we describe monosynaptic long-range GABAergic projections from PFC to hippocampus. These preferentially inhibit vasoactive intestinal polypeptide-expressing interneurons, which are known to disinhibit hippocampal microcircuits. Indeed, stimulating prefrontal–hippocampal GABAergic projections increases hippocampal feedforward inhibition and reduces hippocampal activity in vivo. The net effect of these actions is to specifically enhance the signal-to-noise ratio for hippocampal encoding of object locations and augment object-induced increases in spatial information. Correspondingly, activating or inhibiting these projections promotes or suppresses object exploration, respectively. Together, these results elucidate a top-down prefrontal pathway in which long-range GABAergic projections target disinhibitory microcircuits, thereby enhancing signals and network dynamics underlying exploratory behavior.
All data reported in this paper will be shared by the lead contact upon request.
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Custom data analysis code has been deposited in a Github repository and is publicly available as of the date of publication. The URL is listed in the Key Resources table.
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Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
