Jen Peterson (David Redish's Lab)

 Department of Neuroscience at the University of Minnesota, Minneapolis, MN, U.S.A 

I am an undergraduate student in the Redish Lab. In my project we are exploring how systemically administered diazepam modulates the CA1 hippocampal network. Data from silicon probes allows us to record large ensembles and explore changes in local field potential (LFP), population representations, and individual cellular activity from our behaving rats. 

Impact of systemic diazepam on dorsal hippocampal CA1 neural activity
Authors: J. G. PETERSON, A. SHEEHAN, M. T. ERICKSON, C. C. DAMPHOUSSE, A. D. REDISH

Systemic diazepam is a benzodiazepine often prescribed for its anxiolytic effects, acting upon GABAA receptors to increase inhibition. To test the pharmacological validity of the anxiety hypothesis of rat behavior in the predator-inhabited foraging “robogator” task, diazepam (2 mg/kg) or Tween-20 vehicle control was injected systemically (IP) into a cohort of 5 rats (3M, 2F) trained to run past a threatening robot to find food. In both this cohort and previous cohorts, we observed strong reductions in the anxiety-like behaviors under diazepam (Walters et al. Psychopharm 2019, Calvin et al. PLoS Biology 2025). In this cohort, we also observed a dramatic change in dorsal hippocampal (dHC) local field potentials (LFP) under diazepam, including reduced power in the sharp-wave ripple (SWR) band (150-250 Hz), a reduced incidence of SWR events, and changes in the theta cycle (Calvin et al 2025). We also observed changes in gamma power that differed across the hippocampal CA1 layers, consistent with GABAA receptor distributions in CA1. Unfortunately, these data only included LFP signals, and thus effects of diazepam on dHC cellular activity remained unknown. In order to identify effects of diazepam on dHC single unit activity and population representations, 4 rats (4F), implanted with silicon probes in CA1 and previously trained on other tasks, learned to run back and forth on a linear track for alternating food reward. Each day, prior to the rat performing the task, rats were injected systemically (IP) with saline, Tween-20, or diazepam (doses ranging from 1-3 mg/kg). LFP data replicated the changes seen in the first cohort. At all doses, rats resting in a flower pot showed highly relaxed muscle tone. However, once put on the track, rats ran laps normally, particularly at lower doses (1-2 mg/kg). At 3 mg/kg, rats ran fewer laps than controls. Neurophysiological effects showed large individual differences, however, particularly at doses higher than 1 mg/kg, cell firing was reduced while running. After running, fewer SWRs were observed in the post-running rest. To test representation properties, tuning curves were constructed and the represented position was decoded at 100 ms time bins. After normalizing for the number of cells in the recording, the entropy of the decoded representations was higher under diazepam than controls both while running and while at rest at the feeders. Similar results were found when decoding using theta time bins and when decoding on-track SWR events directly. These data suggest that systemic diazepam administration may affect dorsal hippocampal function in ways that may be important for spatial navigation, memory, and consolidation.