Disrupting the medial prefrontal cortex alters hippocampal sequences during deliberative decision making

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Current theories of deliberative decision making suggest that deliberative decisions arise from imagined simulations that require interactions between the prefrontal cortex and hippocampus. In rodent navigation experiments, hippocampal theta sequences advance from the location of the rat ahead to the subsequent goal. To examine the role of the medial prefrontal cortex (mPFC) on the hippocampus, we disrupted the mPFC with DREADDs (designer receptors exclusively activated by designer drugs). Using the Restaurant Row foraging task, we found that mPFC disruption resulted in decreased vicarious trial and error behavior, reduced the number of theta sequences, and impaired theta sequences in hippocampus. mPFC disruption led to larger changes in the initiation of the hippocampal theta sequences that represent the current location of the rat rather than to the later portions that represent the future outcomes. These data suggest that the mPFC likely provides an important component to the initiation of deliberative sequences and provides support for an episodic-future thinking, working memory interpretation of deliberation. NEW & NOTEWORTHY The medial prefrontal cortex (mPFC) and hippocampus interact during deliberative decision making. Disruption of the mPFC impaired hippocampal processes, including the local and nonlocal representations of space along each theta cycle and the initiation of hippocampal theta sequences, while sparing place cell firing characteristics and phase precession. mPFC disruption reduced the deliberative behavioral process vicarious trial and error and improved economic behaviors on this task.

Original languageEnglish (US)
Pages (from-to)1981-2000
Number of pages20
JournalJournal of neurophysiology
Issue number6
StatePublished - Jun 2019

Bibliographical note

Funding Information:
Financial support for this work was provided by National Institute on Drug Abuse (NIDA) grant DA030672 (A. D. Redish), National Institute of Mental Health grant MH080318 (A. D. Redish), as well as a diversity supplement NIDA DA030672S1 (B. J. Schmidt), funding from the Society for Neuroscience Scholars Program (B. J. Schmidt), and an NIH F32 fellowship DA038392 (B. J. Schmidt).

Publisher Copyright:
© 2019 the American Physiological Society.


  • Hippocampus
  • Place cell
  • Prelimbic cortex
  • Theta
  • Vicarious trial and error


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