Research

Dendritic spines are the sites of most excitatory connections in the central nervous system. The central goal of our laboratory is to delineate the molecular and biochemical mechanisms that regulate dendritic spine plasticity in both the normal and diseased brain. In particular, using animal models, we are interested in recapitulating the genetic and biochemical alterations identified in neuropsychiatric disorders to identify brain region-specific aberrations in dendritic spine formation, stability, and experience-dependent remodeling. Additionally, we aim to understand how these regional synaptic changes, in turn, contribute to specific disease-associated behavioral phenotypes. Finally, we are interested in understanding how environmental-based risk factors for neuropsychiatric disease interact with specific genetic susceptibility factors to produce synaptic and behavioral phenotypes.

One approach used by our lab is in vivo viral-mediated gene transfer in which the expression of a gene and associated protein product are manipulated in an individual brain region. Further, within individual brain regions, viral-mediated gene transfer can enable the genetic manipulation of specific neuronal subtypes and specific neuronal populations. Viral approaches have the advantage of directly linking the altered expression/activity of neuropsychiatric disease-associated proteins in a single brain region with specific behavioral endophenotypes. This helps clarify the role of altered dendritic spine morphogenesis in individual brain structures in mediating disease-associated behavioral dysfunction.

While the study of individual brain regions helps demystify the critical structures regulating specific behaviors, complex behaviors are invariably the product of dynamic regulations in the functional connectivity between multiple brain regions. Altered structural and functional connections between brain regions, both proximal and distal, are commonly associated with neuropsychiatric disorders. However, the consequences of these alterations on neuronal structure and behavior are seldom known. Using in vivo circuit-based manipulations (e.g., optogenetics and DREADDs), our laboratory aims to understand how altered interbrain region connectivity patterns identified in neuropsychiatric diseases impact dendritic spine formation, maturation, and stability, and the consequent effects on behavioral functioning.

Using the approaches described above, our laboratory seeks to understand how altered structural and functional plasticity in brain reward circuits potentially give rise to the social motivational impairments characteristic of autism spectrum disorders. In addition, our laboratory aims to better understand the etiology of executive processing (e.g., working memory) dysfunction in schizophrenia by the investigation of specific prefrontal cortical circuits.