Synaptic Integration in Neurons of the Thalamic Reticular Nucleus

丘脑网状核神经元的突触整合

基本信息

项目摘要

DESCRIPTION (provided by applicant): GABAergic neurons of the thalamic reticular nucleus (TRN) have critical roles in controlling sensory processing, in generating synchronous oscillations in thalamocortical networks, and in modulating attention. TRN neurons are rapidly activated by glutamatergic inputs that originate in both cortex and thalamus. In turn, they form powerful inhibitory connections with relay cells in several dorsal thalamic nuclei. TRN neuronal output is regulated by networks of local GABAergic synapses as well as by a system of cholinergic afferents that originate in the brainstem and basal forebrain. The long-term goal of this proposal is to better understand the complex roles TRN plays in regulating thalamic activity. The primary objective is to determine how distinct types of GABAergic and cholinergic synaptic inputs control the output of TRN neurons. The central hypothesis states that both GABAergic and cholinergic inputs can powerfully excite TRN neurons and that specific types of dendritically expressed voltage- and calcium gated conductances are involved in the integration of these inputs. The rationale for the proposed research is that understanding the mechanisms that underlie GABAergic and cholinergic signaling in the TRN will aid in revealing the principles underlying network activity in the TRN, ultimately translating into a better understanding of the specific processes leading to TRN dysfunction associated with a number of neurological diseases. Guided by strong preliminary data, the central hypothesis will be tested by three specific aims: 1) Determine the functional properties of GABAergic synaptic transmission in the TRN. Under this aim, both the mechanisms underlying GABA-evoked activation of TRN neurons as well as its functional consequences on relay cell activity will be examined. 2) Determine the functional role of dendritic voltage- and calcium activated conductances. Under this aim, the contribution of T-type calcium and SK potassium conductances for the processing of GABAergic synaptic inputs will be tested. 3) Determine the properties of cholinergic inputs to TRN. Under this aim, the dynamics underlying activation of postsynaptic nicotinic and muscarinic receptors by the release of endogenous acetylcholine in the TRN will be examined. This approach will lead to novel insights concerning synaptic transmission in the thalamus. The proposed research is significant, because it is expected to advance and expand understanding of how distinct synaptic inputs shape network activity in TRN. PUBLIC HEALTH RELEVANCE: The thalamic reticular nucleus is a brain area critical for the processing of sensory inputs and for the regulation of attention. This proposal will determine how local GABAergic synapses and afferent cholinergic synaptic inputs regulate activity in TRN neurons. Results from these studies will help to identify novel therapeutic targets to treat neurological diseases associated with TRN dysfunction, such as absence seizures or schizophrenia.
描述(由申请人提供):丘脑网状核(TRN)的GABA能神经元在控制感觉处理、在丘脑皮质网络中产生同步振荡和调节注意力方面具有关键作用。TRN神经元被起源于皮层和丘脑的多巴胺能输入迅速激活。反过来,它们与丘脑背核中的中继细胞形成强大的抑制性连接。TRN神经元输出受局部GABA能突触网络以及起源于脑干和基底前脑的胆碱能传入系统调节。这项提案的长期目标是更好地了解TRN在调节丘脑活动中发挥的复杂作用。主要目的是确定不同类型的GABA能和胆碱能突触输入如何控制TRN神经元的输出。中心假设指出,GABA能和胆碱能输入都可以有力地激发TRN神经元,并且特定类型的树突表达的电压门控电导和钙门控电导参与这些输入的整合。拟议研究的基本原理是,了解TRN中GABA能和胆碱能信号传导的机制将有助于揭示TRN中网络活动的基本原理,最终转化为更好地理解导致TRN功能障碍的特定过程与许多神经系统疾病相关。在强有力的初步数据的指导下,中心假设将通过三个具体目标进行检验:1)确定TRN中GABA能突触传递的功能特性。在这个目标下,GABA诱发的TRN神经元激活的机制以及其对中继细胞活性的功能后果将被检查。2)确定树突电压和钙激活电导的功能作用。在这个目标下,T型钙和SK钾电导的GABA能突触输入的处理的贡献将被测试。3)确定TRN的胆碱能输入的性质。根据这一目标,动力学潜在的激活突触后烟碱和毒蕈碱受体的释放内源性乙酰胆碱的TRN将被检查。这种方法将导致新的见解有关丘脑中的突触传递。这项研究意义重大,因为它有望推进和扩展对不同突触输入如何塑造TRN网络活动的理解。 公共卫生相关性:丘脑网状核是处理感觉输入和调节注意力的关键脑区。这个建议将确定当地GABA能突触和传入胆碱能突触输入如何调节TRN神经元的活动。这些研究的结果将有助于确定新的治疗靶点,以治疗与TRN功能障碍相关的神经系统疾病,如失神发作或精神分裂症。

项目成果

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Michael Beierlein其他文献

Michael Beierlein的其他文献

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{{ truncateString('Michael Beierlein', 18)}}的其他基金

Corticothalamic circuits mediating behavioral adaptations to unexpected reward omission
皮质丘脑回路介导对意外奖励遗漏的行为适应
  • 批准号:
    10734683
  • 财政年份:
    2023
  • 资助金额:
    $ 33.25万
  • 项目类别:
Thalamic Reticular Nucleus Dysfunction in Alzheimer's Disease
阿尔茨海默病中的丘脑网状核功能障碍
  • 批准号:
    10058690
  • 财政年份:
    2020
  • 资助金额:
    $ 33.25万
  • 项目类别:
Thalamic Reticular Nucleus Dysfunction in Alzheimer's Disease
阿尔茨海默病中的丘脑网状核功能障碍
  • 批准号:
    10396654
  • 财政年份:
    2020
  • 资助金额:
    $ 33.25万
  • 项目类别:
Thalamic Reticular Nucleus Dysfunction in Alzheimer's Disease
阿尔茨海默病中的丘脑网状核功能障碍
  • 批准号:
    10612400
  • 财政年份:
    2020
  • 资助金额:
    $ 33.25万
  • 项目类别:
Thalamic Reticular Nucleus Dysfunction in Alzheimer's Disease
阿尔茨海默病中的丘脑网状核功能障碍
  • 批准号:
    10221592
  • 财政年份:
    2020
  • 资助金额:
    $ 33.25万
  • 项目类别:
Synaptic Integration in Neurons of the Thalamic Reticular Nucleus
丘脑网状核神经元的突触整合
  • 批准号:
    8787517
  • 财政年份:
    2012
  • 资助金额:
    $ 33.25万
  • 项目类别:
Synaptic Integration in Neurons of the Thalamic Reticular Nucleus
丘脑网状核神经元的突触整合
  • 批准号:
    8413847
  • 财政年份:
    2012
  • 资助金额:
    $ 33.25万
  • 项目类别:

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