Inhibition, Synapses, and Spike-Timing: Identification and disruption of pyramidal cell-interneuron interactions in SPW-Rs.

The neural circuitry responsible for memory consists of complex components with dynamic interactions. In hippocampal area CA1, interactions between excitatory pyramidal cells and inhibitory interneurons shape ensemble activity which encodes sequential experience. An extremely diverse set of inhibitory interneurons, with variation in gene expression, synaptic targeting, state-dependent activity, and connectivity, contribute substantially to circuit activity, such as theta and sharp wave-ripple oscillations. The precise roles of each interneuron group is not well understood, though characterization of their activity reveals mechanisms underlying hippocampal circuit computation. In this dissertation, I aim to identify and disrupt interactions between pyramidal cells and local interneurons to clarify their role in shaping cell assembly activity. We characterized axo-axonic cell activity in sharp wave-ripples, and compared their control of pyramidal cell activity and ripple events to parvalbumin expressing neurons. We identified pyramidal cell-interneuron interactions during ripples, suggesting they serve as lateral inhibitors between cell assemblies. We additionally developed and implemented a novel neural device to explore the role of cannabinoid disruption of hippocampal oscillations and organization of assemblies in vivo in awake animals. We demonstrate that cannabinoid receptor type 1 within CA1 is responsible for suppression of theta and SPW-Rs. We also found that cannabinoid activation within CA1 circuitry, regardless of muted input from CA3, was sufficient to disrupt sharp wave-ripples, likely through interference of pyramidal cell-interneuron interactions. The work in this dissertation provides insight suggesting that interneuron activity must be studied at the spiking timescale to characterize their control over cell assembly activity.