P50MH132775

Control of Synaptic Circuits by Small GTPase Pathways - Summary – Overall a major goal of NIMH is to understand the neurobiology underlying common cognitive and behavioral deficits associated with mental disorders. Such behavioral deficits, as well as action plans executed in response to novel sensory experiences, are gated by cognitive processing within neocortical circuits.

It is expected that a mechanistic and multi-level biological understanding of how cortical circuits are built and refined during development will reveal molecular targets for future therapeutic strategies to treat mental disorders. Thus, the goal of this center is to understand how gene expression and associated gene function within key neuronal subtypes regulates neurobiological substrates required to form cortical circuits that enable decision-making and behavioral adaptations.

A Conte Center will provide rapid and efficient bidirectional flow of information and tools, as well as synergy and integration that could not be achieved using individual grants. Ras and Rho-like small GTPases play fundamental biological roles within neurons by controlling cell-autonomous growth-related signaling pathways and orchestrating neuronal circuit assembly and function.

Gefs and Gaps are direct upstream regulators of small GTPase signaling, and within neurons, orchestrate cellular migration, neuronal morphogenesis, synaptic connectivity, synaptic plasticity triggered in response to novel sensory experience, in vivo neural circuit function, and associated behavioral adaptations. Gefs and Gaps as exemplar biological entry points for understanding how cellular GTPase signaling shapes neural circuits that facilitate adaptive behaviors.

However, it is unknown how their expression and function within specific neuronal subtypes and defined developmental windows drive cortical circuit refinement to impact cognitive processing and associated behaviors. To close this knowledge gap, our team is proposing an integrated, interdisciplinary, multi-level “Center for GTPase Regulation of Neuronal Cell Biology and Behavior” to study the roles of GTPase signaling in cortical neural circuit with the goal of understanding fundamental principles that drive the hierarchical organization of brain circuits that underlie complex behaviors.

Comprised of investigators with expertise that spans all major levels of brain function – molecular, synaptic, cellular, circuit, system, and behavior – the impact of our center will be to mechanistically connect the regulation of GTPase signaling within distinct neuronal subtypes to the assembly and function of behavioral circuits associated with mental disorders.

Northwestern University

NOT APPLICABLE

93.242 - Mental Health Research Grants

National Institute of Mental Health (NIMH) [HHS - NIH]

Illinois United States

State-Wide

Silvio O. Conte Centers for Basic Neuroscience or Translational Mental Health Research (P50 Clinical Trial Optional) (PAR-22-155)