Nicotinic modulation of deep layer inhibitory neurons for visual cortical plasticity

烟碱调节深层抑制神经元对视觉皮层可塑性的影响

• 批准号: 10432037
• 负责人: Hirofumi Morishita
• 金额: $ 51.65万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432037
• 关键词: Acute; Adolescent; Adult; Affect; Amblyopia; Behavior; Behavioral Assay; Biological Assay; Brain; Brain Diseases; Brain Injuries; Cells; Characteristics; Data; Discrimination; Drosophila acetylcholine receptor alpha-subunit; Elderly; Electrophysiology (science); Elements; Event; Exercise; Gene Expression; Genetically Engineered Mouse; Goals; Human; Hypersensitivity; In Vitro; Interneurons; Knock-in; Knock-in Mouse; Knock-out; Knockout Mice; Measurement; Measures; Mediating; Modeling; Molecular; Mus; Neurodevelopmental Disorder; Neurons; Ocular Dominance; Parvalbumins; Physiological; Population; Positioning Attribute; Pyramidal Cells; Recovery; Role; Running; Sensory; Signal Transduction; Slice; Somatostatin; Synapses; System; Testing; Traumatic Brain Injury; Visual; Visual Acuity; Visual Cortex; Visual evoked cortical potential; Water; area striata; base; cell type; critical period; electric impedance; experience; extracellular; functional disability; in vivo; inhibitory neuron; injury and repair; knock-down; monocular deprivation; neuroregulation; novel; optogenetics; patch clamp; positive allosteric modulator; prevent; receptor; relating to nervous system; response; selective expression; therapeutic evaluation; visual plasticity

Project Summary: The decline of cortical plasticity due to closure of the juvenile-specific critical period is the key impedance of recovery from neurodevelopmental disorders and brain trauma in later life. Neuromodulatory systems are abundant in the adult cortex and well-positioned to orchestrate experience-dependent physiological events to prompt robust plasticity. However, an increasingly recognized complexity of neuromodulatory circuits as well as the diversity of neuron subtypes pose a challenge to identify a specific neuromodulatory system and their cortical target to precisely restore plasticity. The goal of this study is to identify novel molecular and circuit targets for inducing neuromodulatory changes in the adult brain, to reactivate juvenile-like plasticity for treating brain disorders with enduring functional impairments. Using ocular dominance plasticity, a prevailing primary visual cortex critical period plasticity model, We will test the hypothesis that, among various possible combinations of neuromodulatory systems, and their cortical targets, nicotinic ACh modulation and somatostatin expressing interneurons in the deep layer of primary visual cortex expressing specific type of nicotinic ACh sub-type as a novel combination of neurmodulatory circuit elements to induce rapid local circuit modulation to restore juvenile-like visual cortex plasticity and recovery from Amblyopia in adulthood. We will test this hypothesis by taking full advantage of the recently developed genetically-engineered mouse lines to achieve sub-population and cortical-layer-specific circuit-selective manipulation and measurement of gene expression or neural activity beyond conventional cell-type level analysis in combination of in vivo extracellular and in vitro slice electrophysiology with optogenetics, chemogenetics, and behavior assay. In Aim1, we will examine the contribution of specific nAChR subuniton inducing experience-dependent rapid change of deep layer interneurons to trigger ocular dominance plasticity. In Aim2, we will dissect the excitatory and inhibitory circuit mechanisms regulated by deep layer SST interneurons to trigger ocular dominance plasticity. In Aim3, we will examine the extent of recovery from Amblyopia by modulating nAChR in deep layer interneurons. Successful completion of this project will illuminate new molecular and circuit mechanisms that gate the initial cascade triggering cortical plasticity, which will have direct implications for Amblyopia, a condition with limited adult-applicable treatment affecting 2–5% of the human population, but also for brain injury repair, sensory recovery, and the treatment of neurodevelopmental disorders with sensory perceptual deficits.

项目摘要：由于幼体特异性关键期的关闭，导致皮质可塑性下降

项目成果

Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

• DOI: 10.1016/j.neuron.2021.02.001
• 发表时间: 2021-04-07
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Norman KJ;Riceberg JS;Koike H;Bateh J;McCraney SE;Caro K;Kato D;Liang A;Yamamuro K;Flanigan ME;Kam K;Falk EN;Brady DM;Cho C;Sadahiro M;Yoshitake K;Maccario P;Demars MP;Waltrip L;Varga AW;Russo SJ;Baxter MG;Shapiro ML;Rudebeck PH;Morishita H
• 通讯作者: Morishita H

Neuroplasticity and dysplasticity processes in schizophrenia.

精神分裂症的神经可塑性和发育不良过程。

• DOI: 10.1016/j.schres.2019.03.008
• 发表时间: 2019
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Morishita,Hirofumi;Vinogradov,Sophia
• 通讯作者: Vinogradov,Sophia

Frontal-Sensory Cortical Projections Become Dispensable for Attentional Performance Upon a Reduction of Task Demand in Mice.

• DOI: 10.3389/fnins.2021.775256
• 发表时间: 2021
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Norman KJ;Bateh J;Maccario P;Cho C;Caro K;Nishioka T;Koike H;Morishita H
• 通讯作者: Morishita H

Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy.

• DOI: 10.3389/fnins.2021.710004
• 发表时间: 2021
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Lepow L;Morishita H;Yehuda R
• 通讯作者: Yehuda R

Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation.

• DOI: 10.1126/sciadv.abe1527
• 发表时间: 2021-03
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Falk EN;Norman KJ;Garkun Y;Demars MP;Im S;Taccheri G;Short J;Caro K;McCraney SE;Cho C;Smith MR;Lin HM;Koike H;Bateh J;Maccario P;Waltrip L;Janis M;Morishita H
• 通讯作者: Morishita H