We use rodent models to investigate the physiological mechanisms that underlie information processing and coordinated interactions between multiple brain regions that are necessary for memory and cognition, with a particular focus on hippocampal – prefrontal cortical interactions. The hippocampus is known to be critical for episodic memories, and the prefrontal cortex is involved in executive control, working memory and decision making. Communication between the prefrontal executive system and the hippocampal memory system is key for learning, remembering, planning, prediction and memory-guided decision making. However, the nature of communication between these two regions, the underling neural mechanisms and causal contributions of this pivotal interaction remain largely unknown.

We address these questions using a combination of techniques, including behavior, large scale multielectrode recordings in awake behaving animals, real time detection and perturbation of neural activity patterns, targeted optogenetic interventions, and computational analysis. We have shown that hippocampal replay during awake sharp-wave ripples (SWRs) is critical for spatial memory, and SWRs are associated with coordinated reactivation of hippocampal-prefrontal neurons during memory-guided decision making. This approach thus allows us to characterize the neurophysiological basis of hippocampal-cortical interactions, and also to provide causal evidence linking specific forms of neural activity to behavior and cognition.

We posit that neural dynamics at the ensemble level and network coordination still remains a “missing link” that can bridge between molecular/ cellular processes and behavioral phenomena in our understanding of mechanisms that underlie cognitive function and dysfunction. Our findings provide a crucial foundation to investigate if impairments in physiological network patterns lead to deficits in memory and cognition in disorders that involve hippocampus and prefrontal cortex. Our research will thus provide crucial insight into several neurological and neuropsychiatric disorders involving these two key regions, such as dementia, Alzheimer’s disease, depression, autism and schizophrenia.