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
• 负责人: Michael Beierlein
• 金额: $ 32.09万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8413847
• 关键词: Absence Epilepsy; Acetylcholine; Action Potentials; Area; Attention; Behavioral; Biological Models; Brain; Brain Stem; Calcium; Cell Nucleus; Cells; Chemicals; Complex; Data; Dendrites; Disease Attributes; Dorsal; Electrical Synapse; Functional disorder; Gated Ion Channel; Glutamates; Goals; Knowledge; Lead; Mediating; Membrane; Membrane Potentials; Muscarinic Acetylcholine Receptor; Neocortex; Neurologic; Neurons; Neurotransmitters; Nicotinic Receptors; Optics; Output; Play; Potassium; Potassium Channel; Preparation; Process; Property; Regulation; Research; Rest; Role; Schizophrenia; Sensory; Sensory Process; Shapes; Signal Transduction; Sleep; Slice; Symptoms; Synapses; Synaptic Transmission; System; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Translating; Work; abstracting; basal forebrain; base; cholinergic; cholinergic synapse; gamma-Aminobutyric Acid; information processing; innovation; insight; nervous system disorder; new therapeutic target; novel; postsynaptic; presynaptic; research study; voltage

Project Summary/Abstract 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.

项目总结/摘要 丘脑网状核（TRN）的GABA能神经元在控制感觉神经元的活动中起着重要作用。 处理，在丘脑皮层网络中产生同步振荡，并在调节注意力。 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， 它们与几个丘脑背核中的中继细胞形成强有力的抑制性连接。TRN神经元 输出受局部GABA能突触网络和胆碱能传入系统的调节 起源于脑干和基底前脑这项提案的长期目标是更好地了解 TRN在调节丘脑活动中扮演的复杂角色。主要目标是确定 GABA能和胆碱能突触输入的类型控制TRN神经元的输出。核心假设 指出，GABA能和胆碱能输入都可以强烈地激发TRN神经元， 树突状表达的电压和钙门控电导涉及这些的整合 输入。这项研究的基本原理是， TRN中的胆碱能信号传导将有助于揭示TRN中网络活动的基本原理， 最终转化为对导致TRN功能障碍的特定过程的更好理解 与许多神经系统疾病有关。在强有力的初步数据的指导下， 将通过三个具体目标进行测试：1）确定GABA能突触的功能特性， 在TRN中传输。在这个目标下，GABA诱发TRN激活的机制 神经元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。在这一目标下，T- 将测试用于GABA能突触输入的处理的SK型钙和SK钾电导。 3)确定TRN的胆碱能输入的性质。在这一目标下， 突触后烟碱和毒蕈碱受体的释放内源性乙酰胆碱在TRN将 考察这种方法将导致新的见解有关丘脑中的突触传递。的 拟议的研究是重要的，因为它预计将推进和扩大了解如何不同的， 突触输入塑造TRN中网络活动。