UCLA

The ability of an organism to survive often rests on the degree to which it is able to learn about its environment, separate useful information from noise, and file it away to be rapidly recalled at the appropriate time. For animals in the wild, this often amounts to recalling where food is buried, or what to do to avoid capture when a hawk flies overhead. For humans, our ability to retain and access memories over the years is arguably the crux of what it means to have a sense of self and form a cohesive narrative of our lives. Indeed, some of the most devastating psychiatric and neurological disorders strike directly at this ability. Alzheimer’s disease and other dementias rob individuals of past experiences that form the fabric of their lives and personalities; psychiatric disorders such as schizophrenia dampen a person’s mental acuity and flexibility, as well as the ability to distinguish between important and unimportant information. Ultimately, understanding how memories are encoded and stably stored through time is an important window through which we can better understand the things that make us who we are, and the consequences that occur when this process is disrupted. As such, interrogating the mechanisms underlying memory formation and storage is one of the most pressing topics in neuroscience at the moment. In chapter 1 of this dissertation, I will provide a discussion of concepts foundational to the study of learning and memory, aiming to describe the multiple scales across which neuroscientists study the formation and storage of information, from molecular mechanisms, cellular physiology, synaptic connections, and network activity. I will also discuss the unique aspects of hippocampal anatomy, cellular composition and physiology that have evolved to position this structure as the initial locus of memory traces. Chapter 2 discusses the role of sleep in memory consolidation, aiming to describe the importance of each sleep stage and their unique physiology on facilitating strengthening and storing the labile memory traces formed during waking. In particular, I focus on what modern approaches allowing us to selectively modulate the activity of neural subsets can tell us about the circuit and cellular mechanisms underlying offline consolidation, which may have been obscured by methodological constraints in earlier sleep research. In chapter 3, I describe experiments that investigate the role of a subpopulation of hippocampal interneurons, oriens-lacunosum moleculare (OLM) cells, in promoting sleep-dependent memory consolidation. By inhibiting this cell population selectively during offline periods between task acquisition and recall, we found that OLM cells in the hippocampus are necessary for offline spatial and contextual memory consolidation. Through in vivo recordings of brain activity with and without OLM inhibition, we linked this cell population to oscillatory activity during rapid eye movement (REM) sleep periods. These experiments are among the first to posit a role for OLM cells in sleep-dependent consolidation and provide further evidence for the necessity of sleep to the formation of and maintenance of memories.