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Cellular basis of psilocybin actions in frontal cortex

额叶皮层裸盖菇素作用的细胞基础

基本信息

批准号：
10516272
负责人：
CHUN-HAY ALEX KWAN
金额：
$ 59.83万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-19 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10516272
关键词：
Antidepressive Agents Apical Architecture Attention Behavior Behavioral Biological Brain Chronic stress Cognition Conscious Dendritic Spines Dose Exposure to Goals HTR2A gene Half-Life Hallucinogens Head Image Ketamine Knock-out Major Depressive Disorder Measures Medial Mediating Mental disorders Moods Mus Neocortex Neuronal Plasticity Neurons Perception Pyramidal Tracts Receptor Cell Resolution Rodent Series Serotonin Receptor 5-HT2A Serotonin Receptor 5-HT2C Signal Transduction Stress Structure Testing Therapeutic Vertebral column Virus antidepressant effect base cell type conditional knockout density early phase clinical trial experimental study frontal lobe hippocampal pyramidal neuron in vivo insight neurobiological mechanism neuropsychiatric disorder novel optical imaging receptor relating to nervous system response retrograde transport serotonin receptor two photon microscopy two-photon

项目摘要

PROJECT SUMMARY Psychedelics are compounds that produce an atypical state of consciousness characterized by altered perception, cognition, and mood. Among psychedelics, psilocybin has gained attention recently because early clinical trials indicated potential antidepressant effects, leading to a ‘breakthrough therapy’ designation from the FDA to test psilocybin for major depressive disorder. However, despite the promise, the biological mechanisms underpinning psilocybin’s potential therapeutic action are poorly understood. Our lab employs subcellular- resolution two-photon microscopy to visualize dendritic structure and function in head-fixed mice. The goal of this project is to characterize how a single dose of psilocybin may alter dendritic architecture in the medial frontal cortex of the mouse and the associated cellular mechanisms. The hypothesis is that psilocybin promotes spine formation by activating specific serotonin receptor subtypes and exerts differential effects on distinct subtypes of pyramidal neurons. To test the hypothesis, we propose a series of experiments that combine subcellular-resolution optical imaging, conditional knockouts, and causal perturbations in mice. The results will answer crucial questions regarding psilocybin’s ability to promote structural plasticity in vivo and delineate receptors and cellular factors that underlie the plasticity-promoting actions. We expect the mechanistic insights will be important as the field evaluates psychedelics as a potential treatment option for neuropsychiatric disorders and searches for novel antidepressants.

项目总结