High-density neural recording of dysfunctional memories in animal models of mental disease
Understanding the neural basis of mental diseases such as schizophrenia and autism is a major challenge in neuroscience. One major roadblock is the lack of basic understanding of how neural circuits contribute to the cognitive processes that are impaired in these diseases. A recent focus in patient populations has been on the “default mode network” of brain areas such as prefrontal cortex and hippocampus that are particularly active during quite rest and free thinking. Such areas exhibit marked impairments in patients. Interestingly, activity in the default network is associated with high-level cognitive functions such as episodic memory, imagination, and consideration of the perspectives of others, thus providing a framework for understanding the neural basis of diseases such as schizophrenia and autism. We will investigate a fascinating correlate of this activity in mice, in which the hippocampus represents sequences of locations corresponding to memories of previously experienced behavioral trajectories through space, but on a 20-fold faster timescale. We will explore how this activity is disrupted in models of cognitive disease, and probe possible molecular mechanisms for this disruption. We will further use powerful genetic techniques to gain experimental control over these activity patterns in the brain. These studies will yield fundamental insights into mechanisms of high-level cognition, with the potential for developing and testing therapeutic interventions for cognitive disease.