A5044953321- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Treatment of Major Depression
- Neural dynamics and brain function
- Protein Tyrosine Phosphatases
- Advanced Fluorescence Microscopy Techniques
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Memory and Neural Mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer Treatment and Pharmacology
- Genetic Syndromes and Imprinting
- Signaling Pathways in Disease
- Pharmacological Receptor Mechanisms and Effects
- Neuroendocrine regulation and behavior
- RNA regulation and disease
- Photoreceptor and optogenetics research
- Neurotransmitter Receptor Influence on Behavior
- Alcoholism and Thiamine Deficiency
- Galectins and Cancer Biology
- Bioenergy crop production and management
- Cellular transport and secretion
- Circadian rhythm and melatonin
- Neurogenesis and neuroplasticity mechanisms
- Phosphodiesterase function and regulation
Yale University
2018-2022
Leibniz Institute for Neurobiology
2013-2017
A single subanesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment mood disorders. Ketamine increase extracellular glutamate synaptic formation prefrontal cortex, but initial cellular trigger that initiates this ketamine's behavioral has not been identified. To address question, we used combination viral shRNA conditional mutation to produce cell-specific...
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated mPFC activity. The contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates rapid antidepressant actions ketamine. Here we tested two major subtypes, Drd1 Drd2 dopamine receptor expressing neurons found that activating cells produces long-lasting anxiolytic...
Abstract A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. particular, somatostatin-expressing (SST) selectively inhibit dendrites regulate synaptic inputs, yet their response to systemic NMDAR antagonism is...
Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates signaling via binding to upstream regulator sestrin. Here, we examined antidepressant actions NV-5138, a novel highly selective small molecule modulator sestrin penetrates blood brain barrier. The results single dose NV-5138 produced...
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked mutations in components regulators of Ras signaling pathway. Approximately 50% cases are caused PTPN11. However, molecular mechanisms underlying impairments patients still poorly understood. Here, we report generation characterization a new conditional mouse strain that expresses overactive...
Abstract N-methyl-D-aspartate receptor (NMDAR) modulators have recently received increased attention as potential therapeutics for posttraumatic stress disorder (PTSD). Here, we tested a novel NMDAR-positive modulator, NYX-783, in the following two rodent models of PTSD: an auditory fear-conditioning model and single-prolonged (SPS) model. We examined ability NYX-783 to reduce subsequent fear-based behaviors by measuring enhanced fear extinction reduced spontaneous recovery (spontaneous...
Abstract A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and then more sustained antidepressant effects. key targeted brain region is the prefrontal cortex, prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as may act preferentially on GABAergic neurons. However, cortical neurons are heterogeneous. In particular, somatostatin-expressing (SST) interneurons selectively inhibit dendrites regulate synaptic inputs, yet...
Dysregulation of the glutamatergic system underlies pathophysiology depression.Both negative and positive modulation NMDARs exert rapid sustained antidepressant effects by reversing dysregulated system.Research in past decades has identified key signaling pathways activated these acting antidepressants.Here, we review converging mechanisms shared antidepressants discuss recent progress on distinct actions NMDAR antagonists modulators to trigger actions.
Abstract The SHANK3 gene encodes a postsynaptic scaffold protein in excitatory synapses, and its disruption is implicated neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorder, schizophrenia. Most studies of the neocortex hippocampus have focused on disturbances pyramidal neurons. However, GABAergic interneurons likewise receive inputs presumably would also be target constitutive perturbations. In this study, we characterize prefrontal cortical microcircuit...
Depression and anxiety affect a large portion of society leading to significant social economic costs. Numerous lines evidence suggest that impaired function in the prefrontal cortex (PFC) is key contributor depression, therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated PFC activity. The contains several pyramidal cell subtypes, but it unclear whether particular subtype targeted produce rapid antidepressant response. Here we tested two major...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20634-x
A single subanesthetic dose of ketamine exerts rapid antidepressant-like effects via glutamate efflux, activation mTORC1 signaling, and enhanced synaptic transmission in the medial prefrontal cortex (mPFC); however, initial cellular trigger for these behavioral actions still remains unclear. Here, we used electrophysiology, biochemistry, molecular biology approaches to determine baseline sex differences behavior after GluN2B conditional deletion from Sst-interneurons, effect on chronic...