High-density neural recording of dysfunctional memories in animal models of mental disease

2014 Seed Grant
David J. Foster, Ph.D.
Department of Neuroscience
Johns Hopkins University

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.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
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As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…