BMI Seminar // Nick Robinson: Hippocampal sequences in temporal association memory and information transfer

I will briefly present two projects which utilize the combination of targeted optogenetics and 2-photon calcium imaging to explore the role of hippocampal activity sequences in the formation of episodic memories and their importance for the transmission of information to downstream brain regions. Associating events across time is essential for the formation of episodic memories. The hippocampus may support this ability by generating neural activity sequences which facilitate the encoding of new experiences. Using two-photon calcium imaging, we recorded CA1 activity sequences in mice during an olfactory delayed paired-associates task. Sequences tiled the delay more evenly in running mice and reorganized across learning, progressively tiling the delay more evenly, which correlated with faster learning of new associations. Next, we utilized holographic two-photon optogenetics to drive sequences across the delay during learning. Photostimulation revealed a suppressive surround functional connectivity profile in CA1 and led to imprinting of stimulated neurons into the endogenous sequences, causing photoactivated neurons to encode the new experience. Determining how specific features of neural activity patterns are utilized by downstream circuits requires the ability to perform targeted manipulations with high-fidelity downstream readout. We developed a strategy combining all-optical interrogation with simultaneous high density electrophysiological recordings from multiple brain areas in awake mice. We use this approach to demonstrate that the temporal order of optogenetically driven place cell reactivation sequences differentially impacts activity downstream.