Episodic memory is vital for cognition and behavior in our day to day lives, guiding what we do at any moment using what we know from past experiences. This ability to identify current spatial and temporal context using prior experience is essential for an organism to flexibly adapt its behavior to changing contingencies. This same substrate serves as an abstract cognitive map, systematically mapping arbitrary relations in time and space at multiple timescales. Multiple brain regions coordinate and interact during these key cognitive processes to support memory guided behavior. Among them, the hippocampus is necessary for learning and remembering past experiences, while the prefrontal cortex is critical for consolidating, integrating, and retrieving the information needed to make a decision. Neuronal activity within the hippocampus possesses oscillatory and sequential dynamics, which, along with hippocampally associated regions that echo these properties, are thought to be the basis for these cognitive processes. This thesis explores the importance of these neuronal activity patterns that recapitulate behavior across brain regions, animal and behavior states, and how they interact.
The first of these works investigates how two of these distinct hippocampal activity states, sharp wave ripples (SWRs) and theta-associated sequences, interact during a deliberative decision making behavior called vicarious trial and error (VTE). Our collaborators showed that VTE behavior was inversely related to SWR rate, with presence of SWRs or VTE at respective reward sites or choice points decreasing their subsequent counterparts, while the rate of VTE, and thus behavioral uncertainty, decreased as an animal learned a behavioral rule. My contribution demonstrated that this relation extends into causal manipulation of these activity states, with disruption of SWRs during a working memory dependent spatial alternation task increasing VTE at the choice point. These relationships suggest that these two neuronal phenomena that recapitulate behavior in distinct states interact and complement each other during the information processing underlying cognition.
The second portion of this thesis extends theta mediated mechanisms of temporal coordination to the hippocampal-prefrontal network, showing that theta oscillations are important for processing and communicating spatial information during memory-guided behavior. We show that prefrontal population activity encodes current position of the animal on a theta-cycle timescale during behavior, and that this coding of spatial position is parallel with hippocampal representations. Further, we find that a finer grained consideration of this theta-phase within cycle improved both prefrontal and hippocampal representations of spatial position to equivalent levels while maintaining coherent coding. This physiological theta-mediated mechanism for coordination of spatial representations provides a basis for exploring how theta oscillations organize and manipulate underlying memory structure.
Finally, we consider and extend the role of sequential theta dynamics during spatial working memory behavior to subsequent REM sleep. We report the existence of REM theta sequences, sequential reactivations of place cells in REM theta that parallel waking theta sequences. We find that wake and REM theta sequences develop rapidly with experience, recapitulating behavioral sequences of compressed space in both the forward and reverse directions throughout learning. These REM sleep theta sequences exhibit a balance of forward and reverse sequences in contrast to predominantly forward wake theta sequences. Finally, we find that a neuronal population known to shift preferred theta phases in REM transiently participates in REM theta sequences only when behavior asymptotes and the task is learned. These novel findings are a first attempt at describing the function of REM and theta associated REM activity in the hippocampal circuit, and provide evidence that REM sleep can support sequence reactivation for consolidation of representations necessary for memory guided behavior.
Taken together, the works in this thesis explore some of the ways in which theta-paced neuronal activity influences circuit function and supports cognition and animal behavior, providing further inroads for studying the influence of theta dynamics on underlying neural substrates in the hippocampus and beyond.
|Advisor:||Jadhav, Shantanu P.|
|Commitee:||Katz, Donald B., Miller, Paul, Redish, A. David|
|School Location:||United States -- Massachusetts|
|Source:||DAI-B 82/3(E), Dissertation Abstracts International|
|Keywords:||Bayesian, Hippocampus, Prefrontal cortex, REM, Sequences, Theta|
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