Projects & Cores

Project 1

Project Leader: Tallie Z. Baram, MD, PhD

Improving our understanding of the mechanisms by which environmental signals during sensitive early-life periods contribute to mental illness will have profound impact on human health

Improving our understanding of the mechanisms by which environmental signals during sensitive early-life periods contribute to mental illness will have profound impact on human health.

Project 1 will focus on this important problem and will test an innovative concept, that fragmented patterns of maternal signals might be a common denominator of the established, profound influence of the mother on the emotional and cognitive outcome of her progeny. It will use innovative viral-genetic methods and epigenetic tools to probe the underlying mechanisms, and integrate single-neuron discoveries with structural and network analyses of Project 2, Project 3 and Project 4. The resulting discoveries will inform and guide behavioral and imaging studies in the other projects, contributing to identification of potential biomarkers and generation of predictive models for adolescent vulnerabilities.

The aims of Project 1 include:

The aims of Project 1

(1) A. Use mathematical tools (with the BCDM core) to analyze patterns of maternal behaviors in an established model of fragmented care.
B. Building on new data showing vulnerabilities to emotional and cognitive problems already in adolescent rats, identify the onset and trajectories of these vulnerabilities to adulthood.

Aim 1
Use mathematical tools (with the BCDM core) to analyze patterns of maternal behaviors in an established model of fragmented care
Building on new data showing vulnerabilities to emotional and cognitive problems already in adolescent rats, identify the onset and trajectories of these vulnerabilities to adulthood
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Aim 2

(2) In concert with Project 4, test the hypothesis that the basis of altered emotional and cognitive functions resulting from fragmented patterns of maternal signals derives from shifts in the functional connectivity of the involved brain networks.

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Aim 3

(3) Examine for sex dependence of the consequences of fragmented patterns of maternal care.

Aim 4

(4) Probe causal molecular mechanisms in defined brain regions that may underlie the emotional and cognitive consequences of fragmented maternal care patterns. Building on new data and novel technologies, we will look for mechanisms of broad enduring gene expression changes, using CRH as a marker gene. Regulating expression in space and time, we will also test if enhanced CRH expression is necessary and sufficient to mediate the effects of fragmented care; finally, we will determine identities of other involved genes, and the mechanisms regulating enduring changes in gene expression at the chromatin level.

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You can read the Project 1 Summary for a non-technical explanation.

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