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Principal Investigator: TAMARA J. PHILLIPS
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2024
Award: $1,533,881
Funding agency: National Institute on Alcohol Abuse and Alcoholism
Project Summary
This renewal application of the Portland Alcohol Research Center (PARC) proposes funding for Years 26 to 30.
Over the years of its existence, the number of Portland investigators engaged in alcohol research has
increased and their associated research efforts and other mutually supportive interactions have matured.
Historically, the PARC is recognized for its combined expertise directed toward the goals of developing and
applying genetic animal models to interrogate mechanisms associated with acute and chronic effects of
alcohol. The PARC has focused on connecting neurocircuitry and genetics as a unique goal, and the
opportunity now exists to comprehensively test focused hypotheses. The PARC renewal is comprised of 4
Research Projects and 4 Cores. Two Projects (P001, P004) are continuing and 2 are new; 1 Core (C001) is
new. We continue to emphasize phenotypes with translational relevance through cutting-edge genetics and
genomics, and add astrocyte transcriptomics and DNA methylomics. The Overall Center Theme unites the
PARC components: The Role of the Tetrapartite Synapse in Risk for and Response to Alcohol Drinking. Our
coordinated research examines the roles of the extracellular matrix (ECM), perineuronal nets, and brain
circuits/synaptic function, applying transcriptomics and methylomics in our animal models. We consider sex
differences, cognitive flexibility, and individual differences in populations at high genetic risk for alcohol
consumption that may inform protective mechanisms. P001 characterizes the transcriptomic profiles of mice
bred for high vs. low alcohol preference, and for residual individual variation in alcohol preference that persists
after strong directional selection for high intake. Cognitive flexibility, a putative predictor of future alcohol
intake, is examined, and there is a unique focus on the primary cilium. P002 considers the role of astrocyte-
expressed ECM proteins and proteases in alcohol drinking, and of ECM glycosaminoglycans (GAGs) relevant
to neuronal plasticity, including hyaluronic acid (HA). P003 integrates mouse and monkey findings via analysis
of the brain methylome of low and heavy alcohol drinking animals of both species. Compelling novel gene
targets and regulatory regions with a role in synaptic plasticity will be investigated by gene editing, circuit
modifications and functional analysis of excitatory/inhibitory neurotransmission. Finally, P004 also integrates
research in monkeys and mice to characterize corticostriatal functional connectivity and synaptic plasticity
associated with deficits in cognitive flexibility and alcohol intake, and to examine the role of HA. The
Administrative Core (AC001) will provide organizational and oversight services for all components of the
Center. The Animal & Resource Core (C001) will generate mice, conduct behavioral phenotyping, and
generate sequencing data for mouse and monkey samples. The Bioinformatics Core (C002) will provide
analytic and data integration services. The Information Dissemination Core (CD001) continues its K-12
focus, and all investigators will participate in its broader educational and outreach activities.
Terms: <Acute><Address><Alcohol Chemical Class><Alcohol Drinking><Alcohol Phenotype><Alcohol consumption><Alcohols><Animal Genetics><Animal Model><Animal Models and Related Studies><Animals><Applied Genetics><Area><Astrocytes><Astrocytus><Astroglia><Bio-Informatics><Bioinformatics><Biopsy Sample><Biopsy Specimen><Brain><Brain Nervous System><Breeding><CNS plasticity><Categories><Cell Body><Cell Communication and Signaling><Cell Membrane Extensions><Cell Membrane Projections><Cell Membrane Protrusions><Cell Signaling><Cell Surface Extensions><Cell Surface Projections><Cell Surface Protrusions><Cell-Extracellular Matrix><Cells><Chronic><Cilia><Cognitive><Complex><Corpus Striatum><Corpus striatum structure><DNA><Data><Deoxyribonucleic Acid><Differences between sexes><Differs between sexes><Disease><Disorder><ECM><Education and Outreach><Education and Training><Encephalon><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Esteroproteases><EtOH drinking><EtOH use><Extracellular Matrix><Extracellular Matrix Proteins><Family Medical History><Family Medical History Epidemiology><Family history of><Female><Funding><Future><Gene Targeting><Genes><Genetic><Genetic Risk><Genetic Structures><Genetic analyses><Genomics><Glycosaminoglycans><Goals><Heavy Drinking><Human Resources><Hyaluronic Acid><Impairment><Individual><Individual Differences><Information Dissemination><Instruction and Outreach><Intake><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Investigation><Investigators><K-12 student><K12 student><Length><Literature><Manpower><Measures><Mice><Mice Mammals><Modality><Modeling><Modification><Monkeys><Mucopolysaccharides><Murine><Mus><Nerve Cells><Nerve Impulse Transmission><Nerve Transmission><Nerve Unit><Neural Cell><Neurocyte><Neuronal Plasticity><Neuronal Transmission><Neurons><Neurosciences><Nucleic Acid Regulator Regions><Nucleic Acid Regulatory Sequences><Outcome><Peptidases><Peptide Hydrolases><Phenotype><Population><Process><Protease Gene><Proteases><Proteinases><Proteolytic Enzymes><R-Series Research Projects><R01 Mechanism><R01 Program><Regulatory Regions><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Residual><Residual state><Resources><Risk><Rodent><Rodentia><Rodents Mammals><Role><Sampling><Seasons><Services><Sex Differences><Sexual differences><Signal Transduction><Signal Transduction Systems><Signaling><Striate Body><Striatum><Structure><Surface><Synapses><Synaptic><Synaptic plasticity><Talents><Techniques><Technology><Testing><Training and Education><Training and Outreach><Treatment Efficacy><Tutoring and Outreach><Variant><Variation><access to alcohol><addiction><addictive disorder><alcohol access><alcohol accessibility><alcohol availability><alcohol consequences><alcohol effect><alcohol ingestion><alcohol intake><alcohol product use><alcohol related research><alcohol research><alcohol response><alcohol use><alcohol use disorder><alcoholic beverage consumption><alcoholic drink intake><alcoholic phenotype><analytical method><astrocytic glia><axon signaling><axon-glial signaling><axonal signaling><behavior phenotype><behavioral genomics><behavioral phenotyping><biological signal transduction><central nervous system plasticity><chronic EtOH drinking><chronic alcohol consumption><chronic alcohol drinking><chronic alcohol ingestion><chronic alcohol use><chronic ethanol consumption><chronic ethanol drinking><chronic ethanol ingestion><cognitive performance><data integration><dissemination of results><drink heavily><drinking behavior><epigenetically><ethanol accessibility><ethanol availability><ethanol consumption><ethanol drinking><ethanol effect><ethanol ingestion><ethanol intake><ethanol product use><ethanol research><ethanol response><ethanol use><ethanol use disorder><excessive alcohol consumption><excessive alcohol ingestion><excessive alcohol intake><excessive drinking><excessive ethanol ingestion><extreme drinking><flexibility><flexible><genetic analysis><genetic regulatory element><genome editing><genomic editing><genomic profiles><glia signaling><glial signaling><global gene expression><global transcription profile><heavy alcohol use><high risk><individual heterogeneity><individual variability><individual variation><inhibitory neuron><intervention efficacy><interventional strategy><male><methylome><methylomics><model of animal><nerve signaling><neural><neural adaptation><neural circuit><neural circuitry><neural plasticity><neural signaling><neuroadaptation><neurocircuitry><neuronal><neuronal signaling><neuroplastic><neuroplasticity><neurotransmission><non-human primate><nonhuman primate><novel><personnel><post-synaptic nerves><post-synaptic neurons><postsynaptic nerves><postsynaptic neurons><pre-synaptic nerve><pre-synaptic neurons><preference><presynaptic nerve><presynaptic neurons><response to alcohol><response to ethanol><reward circuitry><segregation><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social role><striatal><synapse><synapse function><synaptic circuit><synaptic circuitry><synaptic function><therapeutic efficacy><therapy efficacy><tool><transcriptome><transcriptome profiling><transcriptomic profiling><transcriptomics>