Afferent Regulation of Prefrontal Maturation during Adolescence

青春期前额叶成熟的传入调节

基本信息

  • 批准号:
    10661841
  • 负责人:
  • 金额:
    $ 39.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-07-08 至 2027-04-30
  • 项目状态:
    未结题

项目摘要

Abstract Adolescence is a vulnerable period of postnatal development for the onset of major psychiatric disorders where the prefrontal cortex (PFC) is involved. According to the NIMH Council's Workgroup Report, many psychiatric disorders can only be understood as an interaction between brain development and susceptibility to risk factors. Although many progresses have been made in the field during the past few years, a comprehensive understanding of the cellular and circuit level mechanisms regulating the developmental trajectory of neural processes involved in these disorders remains incomplete. Thus, our long-term goal is to identify sensitive developmental processes during adolescence that contribute to the onset of psychiatric disorders where the PFC is compromised. From studies performed during the preceding grant period, we have found that a hallmark of PFC maturation during adolescence is the functional re-calibration of an excitatory-inhibitory (E-I) balance state. In addition to the gain of GABA function, there is a facilitation of GluN2B and GluN2A NMDAR transmission in the PFC that is intimately linked to ventral hippocampal and basolateral amygdalar inputs. Yet, the extent to which coordinated activation of ventral hippocampal and basolateral amygdalar inputs during adolescence are required for the functional maturation of the PFC remains unclear. We will fill this gap in knowledge through the pursuit of 3 Specific Aims. We will use an input-specific chemogenetic strategy to transiently inhibit PFC afferent transmission at 3 non-overlapping adolescent periods to establish the exact window(s) of susceptibility for the gain/functional maturation of the GABA and NMDA synaptic components of the PFC E-I balance and their impact on PFC-dependent behaviors in adulthood. Together, the proposed aims are expected to uncover key neural circuit processes that contribute to the enhanced PFC vulnerability during adolescence to developmental insults. Such knowledge is expected to provide insights on the implementation of new therapeutic interventions to prevent/mitigate the incidence of cognitive and affective deficits often seen in mental illnesses that emerge during adolescence.
摘要 青春期是产后发育的一个脆弱时期,容易发生严重的精神障碍, 前额叶皮层(PFC)也参与其中。根据NIMH理事会的工作组报告,许多精神病患者 疾病只能被理解为大脑发育和风险易感性之间的相互作用 因素尽管在过去几年中在该领域取得了许多进展, 理解调节神经元发育轨迹的细胞和回路水平机制, 参与这些疾病的过程仍然不完整。因此,我们的长期目标是识别敏感的 在青春期的发展过程中,有助于精神疾病的发病, 一等兵已经暴露了从上一个赠款期间进行的研究,我们发现, 青春期PFC成熟的标志是兴奋-抑制(E-I)的功能重新校准。 平衡状态除了GABA功能的增加,GluN 2B和GluN 2A NMDAR也有促进作用。 在PFC中的传递与腹侧海马和基底外侧杏仁核输入密切相关。然而, 腹侧海马和基底外侧杏仁核输入的协调激活程度 青少年期PFC功能成熟所需的时间尚不清楚。我们将填补这一空白, 通过三个具体目标的追求知识。我们将使用输入特异性化学遗传学策略, 在3个不重叠的青春期短暂抑制PFC传入传递,以建立确切的 GABA和NMDA突触成分获得/功能成熟的敏感性窗口 PFC E-I平衡及其对成年PFC依赖行为的影响。共同提出的目标 预计将揭示导致PFC脆弱性增强的关键神经回路过程 青春期到发育期的侮辱预计这些知识将有助于深入了解 新的治疗干预措施,以预防/减轻认知和情感缺陷的发生率, 在青春期出现的精神疾病。

项目成果

期刊论文数量(27)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
CB1 Cannabinoid Receptor Expression in the Striatum: Association with Corticostriatal Circuits and Developmental Regulation.
  • DOI:
    10.3389/fphar.2012.00021
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Van Waes V;Beverley JA;Siman H;Tseng KY;Steiner H
  • 通讯作者:
    Steiner H
Higher Neuronal Facilitation and Potentiation with APOE4 Suppressed by Angiotensin II.
血管紧张素 II 抑制 APOE4 提高神经元促进和增强作用。
  • DOI:
    10.21203/rs.3.rs-2960437/v1
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Scheinman,SarahB;Tseng,KueiY;Alford,Simon;Tai,LeonM
  • 通讯作者:
    Tai,LeonM
Developmental regulation of excitatory-inhibitory synaptic balance in the prefrontal cortex during adolescence.
GPR88 - a putative signaling molecule predominantly expressed in the striatum: Cellular localization and developmental regulation.
GPR88 - 一种假定的信号分子,主要在纹状体中表达:细胞定位和发育调节。
  • DOI:
    10.1016/j.baga.2011.04.001
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    0
  • 作者:
    VanWaes,Vincent;Tseng,KueiY;Steiner,Heinz
  • 通讯作者:
    Steiner,Heinz
Differential regulation of parvalbumin and calretinin interneurons in the prefrontal cortex during adolescence.
  • DOI:
    10.1007/s00429-013-0508-8
  • 发表时间:
    2014-01
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Caballero, Adriana;Flores-Barrera, Eden;Cass, Daryn K.;Tseng, Kuei Y.
  • 通讯作者:
    Tseng, Kuei Y.
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Kuei-Yuan Tseng其他文献

Kuei-Yuan Tseng的其他文献

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{{ truncateString('Kuei-Yuan Tseng', 18)}}的其他基金

Impact of Cannabis on Prefrontal Maturation
大麻对前额叶成熟的影响
  • 批准号:
    10654964
  • 财政年份:
    2023
  • 资助金额:
    $ 39.98万
  • 项目类别:
Monoaminergic regulation of prefrontal cortex inhibition during adolescence
青春期前额皮质抑制的单胺能调节
  • 批准号:
    8644899
  • 财政年份:
    2010
  • 资助金额:
    $ 39.98万
  • 项目类别:
Afferent Regulation of Prefrontal Maturation during Adolescence
青春期前额叶成熟的传入调节
  • 批准号:
    9104556
  • 财政年份:
    2010
  • 资助金额:
    $ 39.98万
  • 项目类别:
Monoaminergic regulation of prefrontal cortex inhibition during adolescence
青春期前额皮质抑制的单胺能调节
  • 批准号:
    8423392
  • 财政年份:
    2010
  • 资助金额:
    $ 39.98万
  • 项目类别:
Monoaminergic regulation of prefrontal cortex inhibition during adolescence
青春期前额皮质抑制的单胺能调节
  • 批准号:
    7992468
  • 财政年份:
    2010
  • 资助金额:
    $ 39.98万
  • 项目类别:
Monoaminergic regulation of prefrontal cortex inhibition during adolescence
青春期前额皮质抑制的单胺能调节
  • 批准号:
    8101337
  • 财政年份:
    2010
  • 资助金额:
    $ 39.98万
  • 项目类别:
Monoaminergic regulation of prefrontal cortex inhibition during adolescence
青春期前额皮质抑制的单胺能调节
  • 批准号:
    8247771
  • 财政年份:
    2010
  • 资助金额:
    $ 39.98万
  • 项目类别:
Cocaine and Mesolimbic Dopamine Electrophysiology
可卡因和中脑边缘多巴胺电生理学
  • 批准号:
    7074554
  • 财政年份:
    1988
  • 资助金额:
    $ 39.98万
  • 项目类别:

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青春期和成人发展期间的认知和非认知能力与职业发展:从遗传和环境结构的角度
  • 批准号:
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Does social motivation in adolescence differentially predict the impact of childhood threat exposure on developing suicidal thoughts and behaviors
青春期的社会动机是否可以差异预测童年威胁暴露对自杀想法和行为的影响
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