UCLA

Working memory is the ability to temporarily store and manipulate information. Many brain regions have been implicated in sensory representations necessary for working memory, but the hippocampus’s sequential activity and well-known role in many types of memory provides a unique model to study the formation of neural ensemble representations. Most hippocampal research has focused on its representations of visuospatial sensory information, which leaves many unanswered questions about how representations of non-spatial and internally generated temporal representations may differ. Therefore, this dissertation focuses on non-spatial sensory and temporal encoding within hippocampal CA1 region, and the hippocampus’s main input areas - lateral and medial entorhinal cortex (LEC and MEC) - during an olfactory working memory task.Chapter 1 will outline key evidence for the roles of entorhinal cortex and hippocampus for working memory and sequential activity that encodes sensory and temporal information. Chapter 2 will describe our recent finding that behavioral timescale synaptic plasticity (BTSP) is a rapid form of plasticity that generalizes to non-spatial tasks with the rapid formation of odor-selective responses in individual CA1 neurons during our olfactory working memory task. Chapter 3 will describe our findings showing how sequential activity in CA1 simultaneously encodes sensory working memory and temporal information in a novel rodent working memory implicit timing task. Chapter 4 will describe our findings that LEC or MEC optogenetic inhibition does not impair learning or performance on our olfactory working memory task even when we make the task dramatically more difficult. Chapter 5 will describe our findings that the inhibitory opsin stGtACR2 can lead to rapid kindling via light pulses that likely are excitatory on axon terminals in the hippocampus when opsin expression was expected to be limited to somas in EC. Altogether, this dissertation contributes to the field’s understanding of how LEC and MEC drive non-spatial and temporal representations in the hippocampus during working memory.