A5075212675- Neuroscience and Neuropharmacology Research
- Cannabis and Cannabinoid Research
- Neurotransmitter Receptor Influence on Behavior
- Sleep and Wakefulness Research
- Neuroendocrine regulation and behavior
- Memory and Neural Mechanisms
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Receptor Mechanisms and Signaling
- Neural dynamics and brain function
- Neurological disorders and treatments
- Epigenetics and DNA Methylation
- Neuroscience and Neural Engineering
- Pharmacological Receptor Mechanisms and Effects
- Zebrafish Biomedical Research Applications
- Nicotinic Acetylcholine Receptors Study
- Cardiac electrophysiology and arrhythmias
- Neuroscience of respiration and sleep
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Alcohol Consumption and Health Effects
- Ion channel regulation and function
- Forensic Toxicology and Drug Analysis
- Cancer, Stress, Anesthesia, and Immune Response
Broad Institute
2022-2024
McGovern Institute for Brain Research
2023-2024
Massachusetts Institute of Technology
2024
Vanderbilt University
2013-2019
Vanderbilt Health
2016-2019
Vanderbilt University Medical Center
2014-2019
Allen Institute for Brain Science
2016
Persistent anxiety after a psychological trauma is hallmark of many disorders. However, the neural circuits mediating extinction traumatic fear memories remain incompletely understood. We show that selective, in vivo stimulation ventromedial prefrontal cortex (vmPFC)-amygdala pathway facilitated memory formation, but not retrieval. Conversely, silencing vmPFC-amygdala impaired formation and reduced extinction-induced amygdala activity. Our data demonstrate critical instructional role for...
Stress is a major risk factor for the development of mood and anxiety disorders; elucidation novel approaches to mitigate deleterious effects stress could have broad clinical applications. Pharmacological augmentation central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy adverse behavioral physiological consequences stress. Here we show that acute foot-shock induces transient state measured 24 h later using light-dark box assay novelty-induced hypophagia...
Abstract Stress is a ubiquitous risk factor for the exacerbation and development of affective disorders including major depression posttraumatic stress disorder. Understanding neurobiological mechanisms conferring resilience to adverse consequences could have broad implications treatment prevention mood anxiety disorders. We utilize laboratory mice their innate inter-individual differences in stress-susceptibility demonstrate critical role endogenous cannabinoid 2-arachidonoylglycerol (2-AG)...
Deficits in social interaction (SI) are a core symptom of autism spectrum disorders (ASDs); however, treatments for deficits notably lacking. Elucidating brain circuits and neuromodulatory signaling systems that regulate sociability could facilitate deeper understanding ASD pathophysiology reveal novel ASDs. Here we found vivo optogenetic activation the basolateral amygdala-nucleus accumbens (BLA-NAc) glutamatergic circuit reduced SI increased avoidance mice. Furthermore,...
Abstract Impairments in fear extinction are thought to be central the psychopathology of posttraumatic stress disorder, and endocannabinoid (eCB) signaling has been strongly implicated learning. Here we utilized monoacylglycerol lipase inhibitor JZL184 selectively augment brain 2-AG levels combined with an auditory cue fear-conditioning paradigm test hypothesis that 2-AG-mediated eCB modulates short-term learning mice. We show systemic impairs a CB1 receptor-dependent manner without...
Mood and anxiety disorders are the most prevalent psychiatric conditions exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective including major depression. We show that traditional COX-2 inhibitors newly developed substrate-selective inhibitor (SSCI) reduce variety of stress-induced behavioral pathologies in mice. found these effects were associated with dampening neuronal...
Ionic conductivity and membrane capacitance are two foundational parameters that govern neuron excitability. Conventional optogenetics has emerged as a powerful tool to temporarily manipulate ionic in intact biological systems. However, no analogous method exists for precisely manipulating cell enable long-lasting modulation of neuronal Genetically targetable chemical assembly conductive insulating polymers can modulate capacitance, but further development this technique been hindered by...
A-Kinase Anchoring Protein 11 (AKAP11) is a shared genetic risk factor for schizophrenia and bipolar disorder, yet its role in the brain remains poorly understood. Through multi-omic analysis of Akap11 mutant mouse brains cultured astrocytes, we identified significant transcriptomic, proteomic, metabolomic alterations. Key findings include upregulation cholesterol fatty acid metabolic pathways, accumulation lipid species such as cholesteryl esters, triacylglycerols, ceramides,...
Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development TC circuit dysfunction. However, mechanistic understanding how dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model ASD reveals neuron hyperexcitability with excessive burst firing temporal mismatch relationship slow cortical rhythms during...
Abstract Optimizing behavioral strategy requires belief updating based on new evidence, a process that engages higher cognition. In schizophrenia, aberrant dynamics may lead to psychosis, but the mechanisms underlying this are unknown, in part, due lack of appropriate animal models and behavior readouts. Here, we address challenge by taking two synergistic approaches. First, generate mouse model bearing patient-derived point mutation Grin2a ( Y700X+/− ), gene confers high-risk for...
Adrenal chromaffin cells (ACCs) are the neuroendocrine arm of sympathetic nervous system and key mediators physiological stress response. Acetylcholine (ACh) released from preganglionic splanchnic nerves activates nicotinic acetylcholine receptors (nAChRs) on causing membrane depolarization, opening voltage-gated Ca2+ channels (VGCC), exocytosis catecholamines neuropeptides. The serotonin transporter is expressed in ACCs interacts with 5-HT1A to control secretion. In addition blocking...
Abstract The burst firing mode of thalamic reticular neurons plays a pivotal role in the generation and maintenance sleep rhythms is implicated sleep-related deficits characteristic neurodevelopmental disorders. Although several models have been developed to date, we currently lack biophysically detailed model able accurately reproduce heterogeneity observed experimentally. Using electrophysiology recordings patch-clamped fluorescently tagged Spp1+ Ecel1+ neurons, leverage previously...