The Silvio O. Conte center dopamine dysfunction in Schizophrenia

nyspifacadefaded The Silvio O. Conte Center
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Participate in a brain imaging study

Project 3
The Cortico-Basal Ganglia Integrative Network: The Circuitry Underlying Striatal Control of the Dorsolateral Prefrontal Cortex

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Adapted from Haber and Knutson (2010) Neuropsychopharmacology, 35(1),pp.4-26.

The general topography of cortical inputs to the striatum and overall functional correlates has given rise to concept of parallel and segregated motivational, cognitive, and motor control basal ganglia (BG) loops. However, accumulating evidence demonstrates a potential role of integration across circuits for striatal mediation of cortical executive function. The overall hypothesis of the Center is that striatal dopaminergic hyperactivity leads to cortical dopamine dysfunction. The goal of P3 is to delineate the circuitry that underlies ventral striatal influence on the cognitive function in dorsolateral prefrontal cortex. The driving hypothesis of this project is that there are both parallel and integrative networks that together comprise a system that underlies striatal dopamine effects on cortical processing. Our laboratory focuses on the cortico-BG circuits that are critical for developing appropriate behavioral responses.

We have shown two key points of integration between limbic and cognitive systems: 1) through a series of striato-nigro-striatal connections in which a set of reciprocal and nonreciprocal connections results in information transfer from limbic to cognitive striatal regions. 2) through the prefrontal cortico-BG network that combines both topographical and non-topographical rules linking distinct components of the cortical circuits to specific striatal and thalamic regions. These nodal points of converging inputs provide subcircuits by which information processing can occur across functional domains. Importantly, there are similar convergent cortical projection patterns in the rodent.

P3 focuses on these circuits and their relationship to parallel and integrative streams of output through the substantia nigra and thalamus via the globus pallidus. There are three specific aims. SA1 will follow the integrative circuit from the specific nodal points of cortical convergence in the striatum to the globus pallidus in relationship pallidal output to the substantia nigra, pars compacta (SAla). SA1b will determine how these connections enter into the parallel pathways of the internal pallidal segment leading back to cortex, via the thalamus. SA2 will delineate of the organization of striatal output from nodes of convergence to the midbrain dopamine system and determine how this input feeds into projections both back to the striatum and to cortex. SA1 and SA2 will focus on cortical areas identified in P1 and P2. SA3 will create 3-D models of nodal point convergence from different cortical areas in mice. This aim will be particularly informative for P4 and P5.

Suzanne Haber is the PI on project 3.

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