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bioRxiv · 10.1101/2023.11.16.567451

Input / Output Relationships for the Primary Hippocampal Circuit.

Gunn, B. G.·Pruess, B. S.·Gall, C. M.·Lynch, G.
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Abstract

The hippocampus is likely the most studied brain region but little is known about signal throughput -- the simplest, yet most essential of circuit operations -- across its multiple stages from perforant path input to CA1. Here we report that single pulse stimulation of the lateral perforant path (LPP) produces a two-part CA1 response generated by projections to CA3 ("direct path") and the dentate gyrus ("indirect path"). The latter was by far the more potent in driving CA1 output because it engaged the massive recurrent collateral system and elicited a series of fEPSPs and spikes in CA3. The mobilization time for this stereotyped sharp wave-like response resulted in surprisingly slow throughput. The circuit did not convey high frequency LPP trains but transmitted single pulses, or bursts of pulses separated by the period of the theta wave. During these activation patterns CA1 output faithfully reproduced a version of the LPP input. We conclude that the basic hippocampal circuit, despite its considerable complexity, has a default mode in which select cortical signals are reliably transferred to output stations. Significance statementThe hippocampus, a brain structure synonymous with episodic memory, is one of the most studied brain regions in neuroscience today. However, despite this intense interest, surprisingly little is known about how signals are transformed and processed by the hippocampal circuit. As a result, there are currently no "bottom up" hypotheses about how the structure supports its physiological function(s). Here, we use a novel brain slice preparation to describe the signal transformations occurring across the primary hippocampal circuit. The results identify novel circuit operations that challenge the notion of the tri-synaptic circuit and provide evidence for frequency-dependent filters that are critical for determining signal throughput. These findings provide an initial link between basic circuit function(s) and events recorded in behaving animals.

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Gunn, B. G., Pruess, B. S., Gall, C. M., Lynch, G.. 2023-11-17. Input / Output Relationships for the Primary Hippocampal Circuit.. https://doi.org/10.1101/2023.11.16.567451

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