The Integrative Neuroscience Initiative on Alcoholism - Neuroimmune consortium (INIA-N) is a multidisciplinary research initiative, funded by the NIAAA, aimed at investigating the genomic, cellular, and behavioral neuroadaptations related to excessive alcohol consumption. The overall premise driving the research supported by INIA-N is that excessive alcohol consumption produces genetic changes and adaptations in immune-related pathways that promote and sustain drinking. INIA-N is comprised of ten interdisciplinary research components that work in concert to identify gene networks and pathways associated with excessive alcohol drinking in humans and animals, and to focus on identifying potential drug targets for treatment of excessive drinking associated with alcohol use disorder.

The Overall INIA-N Goals are:

1) Expand gene expression datasets with the addition of results from single nuclei sequencing and spatial transcriptomics to generate cell-type specific and anatomical transcriptome information. Integrate human cellular transcriptome with human genome wide association studies (GWAS) to map the cellular enrichment of genetic variants associated with alcohol drinking and determine their impact on drinking behavior (COGA collaboration).

2) Define the contribution of specific non-neuronal cell types (astrocytes and microglia) to the molecular and behavioral effects of excessive alcohol consumption through a wide ranging, collaborative investigation of immune related cells of the brain, which have historically been under investigated in the alcohol field.

3) Examine alcohol-induced changes in perineuronal nets and in the abundance and post-translational modifications of extracellular matrix proteins as a mechanism for glial-neuronal cross talk that impacts brain circuits regulating alcohol consumption.

4) Pursue signal transduction and electrophysiological studies of cytokine signaling to understand innate immune mechanisms by which excessive alcohol consumption changes brain function.

5) Apply systems-level, connectomics approaches (live brain imaging and brain-wide histology) to understand the mechanisms by which excessive alcohol consumption changes brain function, with emphasis on the role of our top neuroimmune genes.

6) Prioritize drug targets and compounds for advancement to testing in animals at facilities funded by NIAAA Alcohol Research Resource Awards (R24) and in humans through the NIAAA Division of Intramural Clinical and Biological Research for further translation outside the INIA-N consortium.