Synaptic and dendritic physiology in the prefrontal cortex
前额皮质的突触和树突生理学
基本信息
- 批准号:10532203
- 负责人:
- 金额:$ 50.63万
- 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:2010-01-06 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AnimalsApicalAreaAttention deficit hyperactivity disorderBehaviorCell NucleusCellsCognitiveComplexDataDendritesDistalElectrophysiology (science)Functional disorderGoalsImageInterneuronsMediatingMental disordersMusPhotonsPhysiologyPlayPopulationPrefrontal CortexPrimatesPropertyPyramidal CellsRodentRoleSchizophreniaShapesSignal TransductionSynapsesTestingThalamic NucleiThalamic structureTransgenic MiceWhole-Cell RecordingsWorkcell typecognitive functionexperimental studyinsightneuronal cell bodyneuropsychiatric disordernoveloptogeneticssensory cortexsensory systemtherapeutic targettwo photon microscopytwo-photon
项目摘要
PROJECT SUMMARY
Interactions between the thalamus and prefrontal cortex (PFC) are important for cognitive function in animals
ranging from rodents to primates. The importance of these long-range networks is highlighted by multiple
neuropsychiatric diseases, including schizophrenia and ADHD. However, most of what we know about
thalamo-cortical circuits comes from sensory systems, where primary thalamic inputs arrive in layer 4 (L4). In
contrast, the mouse PFC is an agranular area that lacks L4, and instead receives higher-order thalamic inputs
directly to superficial layers. We recently discovered that the PFC makes reciprocal connections with both the
mediodorsal (MD) and ventromedial (VM) thalamus. These thalamic nuclei support distinct behaviors, but the
cellular, synaptic and circuit mechanisms for their interactions with PFC are poorly understood. We found MD
strongly drives layer 2/3 (L2/3) pyramidal cells, whereas VM inputs contact the dendrites of a subset of L5
pyramidal cells. Interestingly, both inputs also robustly engage inhibitory networks to drive local inhibition
mediated by GABAergic interneurons. The goal of this proposal is to assess how thalamic inputs engage
different populations of superficial interneurons to mediate inhibition in the PFC. In Specific Aim 1, we use
optogenetics and electrophysiology to study how thalamic inputs drive multiple classes of interneurons in
superficial layers. Our preliminary data suggests that MD and VM engage complementary populations of
interneurons located in different sub-layers. In Specific Aim 2, we then use conditional optogenetics to study
how these interneurons contact excitatory and inhibitory cells within and across layers. Our preliminary data
indicate that the interneurons contacted by MD and VM participate in distinct inhibitory and disinhibitory circuits
across multiple layers. Lastly, in Specific Aim 3, we combine 1-photon optogenetics with 2-photon microscopy
to study how specific populations of interneurons mediate the suppression of dendritic Ca2+ spikes. Our
preliminary data reveal that a sub-population of superficial interneurons mediates robust feed-forward inhibition
in the dendrites. Together, the results from our experiments will answer fundamental questions about the
organization of thalamo-cortical circuits and interneurons in the PFC. They will also help identify potential
therapeutic targets for the many neuropsychiatric disorders that arise from disrupted circuitry within the PFC.
项目总结
丘脑和前额叶皮质(PFC)之间的相互作用对动物的认知功能很重要
从啮齿动物到灵长类动物。这些远程网络的重要性从多个方面突显出来
神经精神疾病,包括精神分裂症和多动症。然而,我们所知道的大部分关于
丘脑-皮质回路来自感觉系统,初级丘脑输入到达第四层(L4)。在……里面
相比之下,小鼠的PFC是一个缺乏L4的非颗粒区,而是接受更高阶的丘脑输入
直接延伸到表层。我们最近发现,PFC与两者之间存在相互联系
丘脑内侧背侧(MD)和腹内侧(Vm)。这些丘脑核团支持不同的行为,但
它们与PFC相互作用的细胞、突触和电路机制还知之甚少。我们找到了MD
强烈驱动层2/3(L2/3)锥体细胞,而Vm输入接触L5子集的树突
锥体细胞。有趣的是,这两个输入还强健地接触到抑制网络以驱动局部抑制
由GABA能中间神经元介导。这项提案的目标是评估丘脑的输入如何参与
不同群体的浅层中间神经元在PFC中起到调节抑制的作用。在具体目标1中,我们使用
光遗传学和电生理学研究丘脑输入如何驱动多类中间神经元
浅层。我们的初步数据表明,MD和VM参与了互补的人群
中间神经元位于不同的亚层。在具体目标2中,我们使用条件光遗传学来研究
这些中间神经元如何在层内和层间接触兴奋性和抑制性细胞。我们的初步数据
提示MD和Vm接触的中间神经元参与不同的抑制和去抑制环路
跨越多个层。最后,在具体目标3中,我们将单光子光遗传学与双光子显微镜相结合
研究特定的中间神经元群体如何介导树突状钙尖峰的抑制。我们的
初步数据显示,一个亚群的浅层中间神经元介导了强大的前馈抑制。
在树枝状突起中。总而言之,我们的实验结果将回答关于
前额叶丘脑皮质环路和中间神经元的组织。他们还将帮助确定潜在的
许多神经精神疾病的治疗目标,这些疾病是由PFC内的电路中断引起的。
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)
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Adam G Carter的其他文献
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{{ truncateString('Adam G Carter', 18)}}的其他基金
Thalamus in the middle: computations in multi-regional neural circuits
中间的丘脑:多区域神经回路的计算
- 批准号:
10546504 - 财政年份:2022
- 资助金额:
$ 50.63万 - 项目类别:
Impact of subcortical inputs on frontal cortex via thalamus
皮层下输入通过丘脑对额叶皮层的影响
- 批准号:
10294403 - 财政年份:2022
- 资助金额:
$ 50.63万 - 项目类别:
Thalamus in the middle: computations in multi-regional neural circuits
中间的丘脑:多区域神经回路的计算
- 批准号:
10294397 - 财政年份:2022
- 资助金额:
$ 50.63万 - 项目类别:
Impact of subcortical inputs on frontal cortex via thalamus
皮层下输入通过丘脑对额叶皮层的影响
- 批准号:
10546514 - 财政年份:2022
- 资助金额:
$ 50.63万 - 项目类别:
The impact of drugs of abuse on striatal circuits
滥用药物对纹状体回路的影响
- 批准号:
8767134 - 财政年份:2014
- 资助金额:
$ 50.63万 - 项目类别:
The impact of drugs of abuse on striatal circuits
滥用药物对纹状体回路的影响
- 批准号:
9068059 - 财政年份:2014
- 资助金额:
$ 50.63万 - 项目类别:
Dendritic physiology and calcium signaling in pyramidal neurons of the prefrontal
前额叶锥体神经元的树突生理学和钙信号传导
- 批准号:
7783980 - 财政年份:2010
- 资助金额:
$ 50.63万 - 项目类别:
Synaptic and dendritic physiology in the prefrontal cortex
前额皮质的突触和树突生理学
- 批准号:
8990978 - 财政年份:2010
- 资助金额:
$ 50.63万 - 项目类别:
Synaptic and Dendritic Physiology in the Prefrontal Cortex
前额皮质的突触和树突生理学
- 批准号:
8402157 - 财政年份:2010
- 资助金额:
$ 50.63万 - 项目类别:
Dendritic physiology and calcium signaling in pyramidal neurons of the prefrontal
前额叶锥体神经元的树突生理学和钙信号传导
- 批准号:
8206675 - 财政年份:2010
- 资助金额:
$ 50.63万 - 项目类别:
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