Nicotinic Receptor Influences on Neuronal Physiology in Dorsolateral Prefrontal C
烟碱受体对背外侧前额叶 C 神经元生理的影响
基本信息
- 批准号:8236410
- 负责人:
- 金额:$ 39.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-10 至 2015-11-30
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAgonistAttentionAttention deficit hyperactivity disorderAxonBehavioralCatecholaminesCellsCognitionCognition DisordersCognitiveCuesDataDendritic SpinesDevelopmentDiseaseEye MovementsFamilyGeneticGlutamatesGoalsHumanImpaired cognitionLocationMemory impairmentMental disordersMonkeysN-Methyl-D-Aspartate ReceptorsN-MethylaspartateNeuronsNicotine DependenceNicotine WithdrawalNicotinic AgonistsNicotinic AntagonistsNicotinic ReceptorsNootropic AgentsPatientsPerformancePharmaceutical PreparationsPhysiologicalPhysiologyPlayPositioning AttributePrefrontal CortexPresynaptic TerminalsPrimatesReceptor SignalingRecurrenceResearchRewardsRodentSchizophreniaShort-Term MemorySignal TransductionSubstance abuse problemSynapsesTherapeuticTherapeutic AgentsTimeVentral Tegmental AreaVertebral columnWorkaddictioncell fixationcholinergicclinically significantcognitive functioncomparative efficacyimprovedinterestminimal riskneurochemistryneuropsychiatryoperationreceptorresponsesample fixationsuccesstherapeutic targettransmission processvigilance
项目摘要
DESCRIPTION (provided by applicant): The proposed research will examine nicotinic receptor influences on dorsolateral prefrontal cortex (dlPFC) network physiology, with the goal of developing therapeutic agents to treat mental illness and nicotine addiction. Nicotinic agonists have great potential as cognitive enhancers if agents can be found that strengthen PFC without engaging subcortical addictive mechanisms. a4b2 and a7 nicotinic receptor subtypes are localized on presynaptic terminals in PFC, and a7 receptors are also post-synaptic on spines. a7 receptors are of particular interest, as they're genetically altered in some families with schizophrenia, and may not have reinforcing actions in the VTA. The proposed research will characterize the influence of a4b2 and a7 nicotinic receptors on dlPFC network physiology for the very first time. dlPFC networks excite each other via NMDA receptors to maintain persistent firing over the delay period in a working memory task. Aim 1 will characterize the effects of a4b2 agonists and antagonists on the responses of dlPFC neurons during performance of a spatial working memory task under control and distracting conditions, using iontophoretic application of drug during recording. Aim 2 will characterize the effects of a7 nicotinic agonists and antagonists, while Aim 3 will examine the interaction of nicotinic influences with NMDA receptor actions. Preliminary data indicate that a7 receptor stimulation enhances the task-related firing of both Delay and Fixation cells, and can rescue loss of firing from NMDA receptor blockade, encouraging the development of a7 agonists as cognitive enhancers.
PUBLIC HEALTH RELEVANCE: Disorders such as schizophrenia have devastating effects on patients and their families, and there are currently no treatments for cognitive impairment in this illness. The proposed research may help to develop a new treatment- an alpha7 nicotinic agonist- that can strengthen cognitive function in patients. It is hoped that an alpha7 nicotinic agonist may be able to improve cognition with minimal risk for addiction.
描述(由申请人提供):拟议的研究将检查烟碱受体对背外侧前额叶皮层(dlPFC)网络生理学的影响,目的是开发治疗精神疾病和尼古丁成瘾的治疗药物。如果能发现能增强PFC而不涉及皮层下成瘾机制的药物,那么尼古丁激动剂作为认知增强剂具有很大的潜力。α_4 β_2和α_7烟碱受体亚型位于PFC的突触前末梢,α_7受体也位于突触后棘上。a7受体特别令人感兴趣,因为它们在一些精神分裂症家族中发生了遗传改变,并且可能在VTA中没有增强作用。这项研究将首次描述a4 b2和a7烟碱受体对dlPFC网络生理学的影响。在工作记忆任务中,dlPFC网络通过NMDA受体相互激发,以在延迟期内保持持续放电。目的1将表征在控制和分心条件下,在记录期间使用药物的离子电渗应用的空间工作记忆任务的执行期间,a4 b2激动剂和拮抗剂对dlPFC神经元的反应的影响。目的2将表征α 7烟碱激动剂和拮抗剂的作用,而目的3将检查烟碱影响与NMDA受体作用的相互作用。初步数据表明,α 7受体刺激增强了延迟细胞和固定细胞两者的任务相关放电,并且可以挽救NMDA受体阻断引起的放电损失,从而鼓励α 7激动剂作为认知增强剂的开发。
公共卫生相关性:精神分裂症等疾病对患者及其家庭具有破坏性影响,目前还没有治疗这种疾病的认知障碍的方法。这项拟议中的研究可能有助于开发一种新的治疗方法-α 7烟碱激动剂-可以增强患者的认知功能。人们希望α 7烟碱激动剂能够以最小的成瘾风险改善认知能力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MIN WANG其他文献
MIN WANG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MIN WANG', 18)}}的其他基金
Role of kynurenic acid in higher cognitive deficits: Mechanism and treatment strategies
犬尿酸在较高认知缺陷中的作用:机制和治疗策略
- 批准号:
10715487 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
Nicotinic Receptor Effects on Neurophysiology of Dorsolateral Prefrontal Cortex
烟碱受体对背外侧前额皮质神经生理学的影响
- 批准号:
8773609 - 财政年份:2012
- 资助金额:
$ 39.15万 - 项目类别:
Cholinergic Influences on Neuronal Physiology in Dorsolateral Prefrontal Cortex.
胆碱能对背外侧前额叶皮层神经元生理学的影响。
- 批准号:
9199594 - 财政年份:2012
- 资助金额:
$ 39.15万 - 项目类别:
Nicotinic Receptor Effects on Neurophysiology of Dorsolateral Prefrontal Cortex
烟碱受体对背外侧前额叶皮层神经生理学的影响
- 批准号:
8423715 - 财政年份:2012
- 资助金额:
$ 39.15万 - 项目类别:
Nicotinic Receptor Effects on Neurophysiology of Dorsolateral Prefrontal Cortex
烟碱受体对背外侧前额皮质神经生理学的影响
- 批准号:
8578109 - 财政年份:2012
- 资助金额:
$ 39.15万 - 项目类别:
Cholinergic Influences on Neuronal Physiology in Dorsolateral Prefrontal Cortex.
胆碱能对背外侧前额叶皮层神经元生理学的影响。
- 批准号:
9027155 - 财政年份:2012
- 资助金额:
$ 39.15万 - 项目类别:
Biliteracy development in Chinese and Korean children
中国和韩国儿童的双语发展
- 批准号:
7334214 - 财政年份:2004
- 资助金额:
$ 39.15万 - 项目类别:
Biliteracy development in Chinese and Korean children
中国和韩国儿童的双语发展
- 批准号:
6849640 - 财政年份:2004
- 资助金额:
$ 39.15万 - 项目类别:
Biliteracy development in Chinese and Korean children
中国和韩国儿童的双语发展
- 批准号:
7155553 - 财政年份:2004
- 资助金额:
$ 39.15万 - 项目类别:
Biliteracy development in Chinese and Korean children
中国和韩国儿童的双语发展
- 批准号:
6989102 - 财政年份:2004
- 资助金额:
$ 39.15万 - 项目类别:
相似国自然基金
Agonist-GPR119-Gs复合物的结构生物学研究
- 批准号:32000851
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
相似海外基金
S1PR1 agonistによる脳血液関門制御を介した脳梗塞の新規治療法開発
S1PR1激动剂调节血脑屏障治疗脑梗塞新方法的开发
- 批准号:
24K12256 - 财政年份:2024
- 资助金额:
$ 39.15万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
AHR agonistによるSLE皮疹の新たな治療薬の開発
使用 AHR 激动剂开发治疗 SLE 皮疹的新疗法
- 批准号:
24K19176 - 财政年份:2024
- 资助金额:
$ 39.15万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Evaluation of a specific LXR/PPAR agonist for treatment of Alzheimer's disease
特定 LXR/PPAR 激动剂治疗阿尔茨海默病的评估
- 批准号:
10578068 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
- 批准号:
10933287 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
Targeting breast cancer microenvironment with small molecule agonist of relaxin receptor
用松弛素受体小分子激动剂靶向乳腺癌微环境
- 批准号:
10650593 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
AMPKa agonist in attenuating CPT1A inhibition and alcoholic chronic pancreatitis
AMPKa 激动剂减轻 CPT1A 抑制和酒精性慢性胰腺炎
- 批准号:
10649275 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253
在男性和女性健康志愿者中进行的一项随机双盲安慰剂对照 1 期 SAD 研究,旨在评估 ABCA1 激动剂 CS6253 的安全性、药代动力学和短暂生物标志物变化
- 批准号:
10734158 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation
研究阿片类激动剂治疗 OUD 患者结果的机制:解开睡眠和昼夜节律对渴望和情绪调节的影响
- 批准号:
10784209 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
A novel nanobody-based agonist-redirected checkpoint (ARC) molecule, aPD1-Fc-OX40L, for cancer immunotherapy
一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
- 批准号:
10580259 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
Identification and characterization of a plant growth promoter from wild plants: is this a novel plant hormone agonist?
野生植物中植物生长促进剂的鉴定和表征:这是一种新型植物激素激动剂吗?
- 批准号:
23K05057 - 财政年份:2023
- 资助金额:
$ 39.15万 - 项目类别:
Grant-in-Aid for Scientific Research (C)