Prefrontal-Hippocampal Interactions

Citation

Wierzynski, Casimir M. (2009) Prefrontal-Hippocampal Interactions. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9833Q10. https://resolver.caltech.edu/CaltechETD:etd-05262009-151920

Abstract

Long-term memories are established in the neocortex under the influence of hippocampal activity. The precise circuit mechanisms underlying this process, however, remain poorly understood. According to the dominant paradigm, memories are formed in two stages: first, neocortical activity during awake behavior embeds traces in hippocampal circuits; second, spontaneous hippocampal activity during offline periods, such as sleep, drives synaptic changes across cortical circuits so as to produce a stable, long-term memory trace. Evidence for this two-stage model at the level of neural activity, however, is incomplete. In this thesis we study interactions between the hippocampus and medial prefrontal cortex (mPFC) to elucidate the basic principles of how these brain circuits work in concert in support of long-term memory. Using recordings of single-unit actvity from multi-tetrode arrays in the hippocampus and mPFC of freely behaving rats, we performed two sets of experiments, each addressing one stage of the two-stage model. First, during awake behavior, we find a class of mPFC cells whose firing reflects the strength of a learned association and show that these tend to be strongly modulated by the hippocampus. Second, during sleep, we identify precise spike timing relationships between single mPFC and hippocampal cells that are consistent with information flow from the hippocampus to the prefrontal cortex, and show that these timing relationships are highly dependent on sleep stage. Taken together, these results provide key constraints on the circuit mechanisms of long-term memory formation.

Thesis Files