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Contribution of CA3 sharp-wave ripple oscillations to decision making during complex spatial working memory tasks


Many regions of the brain contribute to memory processing and the subsequent use of stored memories for making informed decisions. The hippocampus is a known region in the medial temporal lobe that can support spatial working memory through interconnections between its distinct sub-regions when the information being held is complex. The synaptic connections in play include the mossy fiber pathway which carries information from the dentate gyrus (DG) to the CA3 recurrent cell layer. Studies have demonstrated that DG lesions effectively impair spatial working memory during complex memory tasks. Local field potential studies have observed the onset of 150-250Hz oscillations, characterized as sharp-wave ripples (SWR), in the CA3 cell layer during working memory. These fast oscillations were correlated with subsequent correct choices and were also found to be DG dependent. Therefore, we hypothesized that working memory is supported by SWR oscillations generated by DG inputs to the CA3 cell layer. Our project aimed to test this casual role through the inhibition of CA3 SWR oscillations in rats during a dentate-dependent working memory task on an 8-arm radial maze. We implemented a SWR detection program to accurately detect high frequency events in CA3 known to be SWRs. Upon detection, electrical stimulation of the ventral hippocampal commissure was triggered, inhibiting SWR generation in CA3 through the prolonged silencing of hippocampal neurons. Behavioral performance was then quantified for stimulation trials and compared to no-stimulation control trials.

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