How does electrical signaling within a neuron and synaptic transmission and plasticity in communications between neurons act to process information within defined neural circuits to give rise to complex cognitive behaviors? And how do alterations in these processes during neuropsychiatric disorders produce abnormal behavior? Our laboratory addresses such questions by focusing on the cortico-hippocampal circuit, which plays a critical role in a number of forms of explicit memory and disease processes.
One long-term goal is to define how the HCN1 hyperpolarization-activated cation channels, which control dendritic integration and excitability in hippocampal pyramidal neurons and modulate transmitter release from inhibitory neurons, regulate information processing in hippocampal circuits to control hippocampal-dependent spatial memory. We are particularly interested in how mutations in HCN1 alter hippocampal activity to produce a severe form of infantile epilepsy.
The second major area of study is focused on how hippocampus regulates social behavior. Through the use of targeted genetic manipulations, we found that one relatively understudied area of the hippocampus, the CA2 region, is essential for social memory, the ability of an animal to remember another of its own species. In addition, we found that CA2 firing also promotes social aggression, and we have defined the neural circuit underlying this action. We are now using in vivo electrophysiology and calcium imaging to characterize how populations of neurons in the CA2 region encode and process social information, during both social exploration and social aggression.
Our results so far indicate that CA2 activity detects social novelty, thereby enabling an animal to distinguish a novel from familiar animal. As alterations in CA2 have been implicated in human neuropsychiatric disorders, including schizophrenia, we study different mouse models of human disease to define how changes in CA2 cellular and network properties may contribute to abnormal social behavior, and how pharmacological and/or optogenetic manipulations of CA2 activity may provide novel therapeutic approaches to disease treatment.