A5009665059- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Epigenetics and DNA Methylation
- Neuroendocrine regulation and behavior
- Tryptophan and brain disorders
- Memory and Neural Mechanisms
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Neuropeptides and Animal Physiology
- Cancer-related molecular mechanisms research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Behavioral and Psychological Studies
- MicroRNA in disease regulation
- Chromatin Remodeling and Cancer
- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Circadian rhythm and melatonin
- Cannabis and Cannabinoid Research
- Renin-Angiotensin System Studies
- Nutrition, Genetics, and Disease
Centre for Addiction and Mental Health
2014-2025
Allen Institute for Brain Science
2018-2025
Icahn School of Medicine at Mount Sinai
2018-2025
Albert Einstein College of Medicine
2022
Washington University in St. Louis
2022
Institute of Cancer Research
2022
University of Toronto
2014-2020
Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and vivo single-neuron calcium imaging, we found that drugs augment dopaminoceptive ensemble activity nucleus accumbens (NAc) disorganize overlapping responses natural rewards a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, single-nucleus RNA sequencing, identified Rheb as molecular substrate regulates...
Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding molecular changes supporting drug-taking and relapse. Here, we develop brain reward circuit-wide atlas opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute exposure, chronic intake, context-induced drug-seeking following...
Women suffer from depression at twice the rate of men, but underlying molecular mechanisms are poorly understood. Here, we identify marked baseline sex differences in expression long noncoding RNAs (lncRNAs), a class regulatory transcripts, human postmortem brain tissue that profoundly lost depression. One such lncRNA, RP11-298D21.1 (which termed FEDORA), is enriched oligodendrocytes and neurons up-regulated prefrontal cortex (PFC) depressed females only. We found virally expressing FEDORA...
Abstract Olfactory processing is thought to be actively modulated by the top-down input from cortical regions, but behavioural function of these signals remains unclear. Here we find that feedback anterior olfactory nucleus pars medialis (mAON) bidirectionally modulates sensitivity and olfaction-dependent behaviours. To identify a limbic tunes this mAON switch, further demonstrate optogenetic stimulation ventral hippocampal inputs sufficient alter
The monoamine neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts an inhibitory influence over motivation, but the circuits mediating this are unknown. Here, we used optogenetic approach to isolate contribution of dorsal raphe nucleus (DRN) 5-HT neurons and innervation mesolimbic dopamine (DA) system motivated behavior in mice. We found that stimulation DRN enhanced downstream release, was not sufficient inhibit operant responding for saccharin, a measure behavior. However,...
The nucleus accumbens (NAc) is a canonical reward center that regulates feeding and drinking but it not known whether these behaviors are mediated by same or different neurons. We employed two-photon calcium imaging in awake, behaving mice found during the appetitive phase, both hunger thirst sensed nearly identical population of individual D1 D2 neurons NAc respond monophasically to food cues fasted animals water dehydrated animals. During consummatory we identified three distinct neuronal...
Abstract DNA cytosine methylation has been documented as a potential epigenetic mechanism of transcriptional regulation underlying opioid use disorder. However, RNA residues, which would drive another level biological influence an epitranscriptomic gene and protein not studied in the context addiction. Here, we probed whether chronic morphine exposure could alter tRNA (m 5 C) resulting expression levels medial prefrontal cortex (mPFC), brain region crucial for reward processing executive...
A hallmark of addiction is the ability drugs abuse to trigger relapse after periods prolonged abstinence. Here, we describe an epigenetic mechanism whereby chronic cocaine exposure causes lasting chromatin and downstream transcriptional modifications in nucleus accumbens (NAc), a critical brain region controlling motivation. We link withdrawal from depletion histone variant H2A.Z, coupled with increased genome accessibility latent priming gene transcription, D1 dopamine receptor–expressing...
Unsuccessful response to several courses of antidepressants is a core feature treatment-resistant depression (TRD), severe condition that affects third patients with treated conventional pharmacotherapy. However, the molecular mechanisms underlying TRD remain poorly understood. Here, we assessed successful vs. unsuccessful ketamine (KET) in chronically stressed mice failed respond initial treatment fluoxetine (FLX) as rodent model and characterized associated transcriptional profiles nucleus...
Neurobiological alterations seen in addiction amplify during abstinence and compromise relapse prevention. Cocaine use disorder (CUD) exemplifies this phenomenon which reward regions such as nucleus accumbens (NAc) undergo withdrawal-associated modifications. While genome-wide transcriptional changes NAc are linked to specific phases, these have not been examined a context- NAc-subregion-specific manner withdrawal vs. extinction. We used cocaine self-administration male rats combined with...
Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable across generations. To date, no studies have investigated differences transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations sperm during chronic social defeat (CSDS) transmit increased susceptibility to phenotypes next generation. demonstrate offspring from stressed fathers depend on paternal category (resilient vs...