This Project Grant award of $1,315,596.00 from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) will fund research to understand the effects of maternal exposure to electronic nicotine delivery system (ENDS) aerosols during pregnancy on addiction-related behaviors and neurocircuitry in offspring. The project, which runs from March 2025 to December 2029, will use animal models to examine the impacts of prenatal ENDS exposure on...
This Project Grant award from the National Institute on Drug Abuse (NIDA), under CFDA Program 93.279 - Drug Use and Addiction Research Programs, provides $201,250 to New York University (NYU) to characterize the synaptic organization and function of cholinergic interneurons in the nucleus accumbens (NAc) core region of the mouse brain. The 2-year project (6/1/2025 - 5/31/2027) will use a combination of anatomy, slice electrophysiology, and optogenetics to examine how diverse excitatory and...
This federal Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $654,500.00 to the University of Tennessee Health Science Center to conduct research on the social factors that influence the initiation and continuation of nicotine addiction. The key research objectives are to investigate how social learning alters the hedonic value of nicotine and facilitates the extinction of nicotine-conditioned...
This federal Project Grant award, funded by the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279), supports research to examine the link between epigenetic processes, mitochondrial function, and drug-seeking behavior in the context of nicotine use disorder. The award, totaling $169,474.00 and spanning August 2024 to July 2029, will be carried out by researchers at the University of Maryland, Baltimore. The key objectives of this research...
This Project Grant award from the National Institute of Mental Health (NIMH), under the Mental Health Research Grants program (CFDA 93.242), provides $438,625 to support research at Stony Brook University examining the role of the vesicular acetylcholine transporter (VACHT) in the pathophysiology of major depressive disorder (MDD). The key objectives are to: 1) assess VACHT levels in individuals with MDD compared to healthy controls using PET imaging, to determine if lower VACHT is associated...
This federal Project Grant award from the National Institute of Mental Health (CFDA 93.242 Mental Health Research Grants) provides $460,855 to New York University School of Medicine to investigate the cellular and circuit mechanisms by which acetylcholine (ACh) promotes associative learning in the primary somatosensory cortex. The key objectives are to: 1) use fluorescent ACh sensors and chemogenetic techniques to study the magnitude and time course of ACh release during different phases of an...
The National Institute of Mental Health (NIMH) awarded a Project Grant under the Mental Health Research Grants program (CFDA 93.242) to Duke University in the amount of $197,660 with a project period from Sep 4, 2024 to Aug 31, 2026. The project aims to characterize early signs of neurobehavioral dysregulation in infants at increased risk for behavioral disorders, such as children with prenatal nicotine exposure. The research will leverage integrative data analysis techniques to identify...
This Project Grant award from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), under the Alcohol Research Programs (CFDA 93.273), provides $375,210 to West Chester University of Pennsylvania to investigate the effects of developmental co-exposure to alcohol and nicotine from e-cigarettes on physiological measures and behavioral development in a mouse model. The key products and services to be delivered include: 1) Examining whether co-exposure to alcohol and nicotine via...
This Project Grant award of $2,594,198.00 from the National Institute on Drug Abuse (NIDA), under the federal Drug Use and Addiction Research Programs (CFDA 93.279), supports research to elucidate the neural circuitry linked to smoking and the genetic influences on it. The study will use the UK Biobank neuroimaging dataset to examine habenula functional connectivity with the salience network and ventral tegmental area, and the influence of genomic variations on this connectivity. It will compare...
This Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), supports research to develop a translational rat model of the neonatal intensive care unit (NICU) experience and its impacts on substance use disorder risk. The $368,315 award to the Georgia State University Research Foundation will: 1) design and test a model combining early pain, resource scarcity, and separation from caregivers to mimic key aspects of...
NICOTINIC MODULATION OF EXCITATORY SYNAPSE DEVELOPMENT IN THE PREFRONTAL CORTEX - PROJECT SUMMARY PRENATAL NICOTINE EXPOSURE (PNE) REMAINS A PRESSING PUBLIC HEALTH CONCERN. AT LEAST 10 PERCENT OF PREGNANT INDIVIDUALS IN THE US REPORT SMOKING CIGARETTES (OR E-CIGS) DURING GESTATION. PNE IS LINKED TO NEURODEVELOPMENTAL DISORDERS SUCH AS ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND AUTISM SPECTRUM DISORDERS. NICOTINE, VIA CHOLINERGIC NICOTINIC ACETYLCHOLINE RECEPTORS (NACHRS), ENHANCES CHOLINERGIC ACTIVITY IN THE PREFRONTAL CORTEX (PFC), DYSREGULATING DEVELOPMENT AND INCREASING THE RISK FOR PFC-LINKED NEURODEVELOPMENTAL DISORDERS. PFC-LINKED NEURODEVELOPMENTAL DISORDERS POINT AT DISRUPTIONS IN SYNAPSE MATURATION LEADING TO SYNAPTIC DYSFUNCTION. HOWEVER, THE MECHANISMS BY WHICH NACHR SIGNALING, AND NICOTINE EXPOSURE, INFLUENCE SYNAPSE MATURATION ARE UNKNOWN. OUR PRELIMINARY STUDIES FOUND THAT CHOLINERGIC DENERVATION IN THE DEVELOPING PFC IMPAIRS EXCITATORY SYNAPSE MATURATION. ADDITIONALLY, WE FOUND NICOTINE TREATMENT PROMOTED SYNAPSE MATURATION IN THE ABSENCE OF GLUTAMATERGIC ACTIVITY. THIS PROPOSAL IS COMPOSED OF TWO AIMS WHICH SEEK TO TEST THE HYPOTHESIS THAT POSTSYNAPTIC NACHR SIGNALING MODULATES EXCITATORY SYNAPSE MATURATION IN THE DEVELOPING PFC. THE FIRST AIM USES A COMBINATION OF INNOVATIVE TECHNIQUES INCLUDING TWO-PHOTON UNCAGING OF GLUTAMATE, CHEMOGENETICS, ELECTROPHYSIOLOGY, AND PHARMACOLOGY TO DETERMINE IF THE UP-REGULATION OF ENDOGENOUS CHOLINERGIC ACTIVITY PROMOTES SYNAPTIC MATURATION. THE SECOND AIM USES TWO-PHOTON, TWO-COLOR UNCAGING OF NICOTINE AND GLUTAMATE, ELECTROPHYSIOLOGY, AND PHARMACOLOGY TO ELUCIDATE THE SYNAPTIC AND MOLECULAR MECHANISMS INVOLVED IN THE NICOTINIC SIGNALING-MEDIATED MATURATION OF SYNAPSES. IN SUM, THE STUDIES OUTLINED IN THIS PROPOSAL WILL SHED LIGHT TO THE CELLULAR, SYNAPTIC, AND MOLECULAR MECHANISMS INVOLVED IN THE NICOTINE-INDUCED MATURATION OF EXCITATORY SYNAPSES. RESULTS FROM THIS PROJECT WILL ADVANCE EFFORTS TOWARDS MITIGATING THE IMPACT OF NEURODEVELOPMENTAL DISORDERS THAT RESULT FROM PNE.