INIA-Neuroimmune

Integrative Neuroscience Initiative on Alcoholism (INIA)-Neuroimmue consortium was funded February 1, 2017 by NIH/NIAAA (FOA AA16-006) to identify the molecular, cellular, and behavioral neuroadaptations that occur in specific brain neurocircuitries that result in excessive alcohol consumption.

This multidisciplinary initiative focuses on the molecular and cellular neuroadaptations in brain addiction circuits associated with the basal forebrain, including reward circuitry in the ventral striatum and dependence circuitry in the extended amygdala and their connections with each other and other structures at lower and higher levels of the CNS.

The predecessor of INIA-Neuroimmune, INIA-West, was originally funded in September 2001. Substantial progress in the development of animal models of excessive alcohol consumption led to a major change in the subgroups and cores for the first competitive renewal. The functions of the different subgroups were distributed into functional Binge and Dependence constructs. The Animal Models Cores took the charge of providing animals/paradigms to individual INIA-Neuroimmune investigators. The emphasis then shifted from developing animal models to genetic refinements of existing animal models with selective breeding. The success with animal models and the issue of overlapping use of animal models led to discussions regarding a functional reorganization of INIA-Neuroimmune.

What evolved is a focus on excessive alcohol consumption that has convergent validity with human alcoholism. The Binge and Dependence constructs have heuristic value and provide a practical means for INIA-Neuroimmune investigators to interact at the molecular, cellular, and systems levels of analysis and utilize animal models of excessive drinking. In the domain of identifying targets for excessive alcohol consumption, INIA-Neuroimmune has completed numerous gene expression studies on genetic animal models and models of excessive drinking. Gene pathways novel to the alcohol field in the excessive drinking domain have been identified.  Many of these genes were related to immune function, yet were changed in the brain, leading to the current emphasis on neuroimmune signaling.

The current consortium focuses on establishing a causal role for these protein targets and potential targets for medication development. These two goals will proceed in parallel. Several mechanistic studies identified targets where small molecules can be tested in the Target Assessment Cores. The Administrative Core will coordinate a multidisciplinary, multicomponent research effort. The overarching hypothesis is that genetic differences and neuroadaptations in reward circuitry are responsible for individual differences in vulnerability to the excessive alcohol consumption.