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
• 负责人: Michael Beierlein
• 金额: $ 33.25万
• 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 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8787517
• 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; 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; neuronal circuitry; new therapeutic target; novel; postsynaptic; presynaptic; research study; sensory input; 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.

项目摘要/摘要 丘脑网状核（TRN）的GABA能神经元在控制感觉方面具有关键作用 处理，在丘脑皮质网络中产生同步振荡，并调节注意力。 TRN神经元被谷氨酸能输入迅速激活，这些输入既起源于皮质和丘脑。反过来， 它们在几个背丘脑核中与中继细胞形成强大的抑制作用。 TRN神经元 输出受局部GABA能突触的网络以及胆碱能传入的系统调节 这起源于脑干和基础前脑。该提议的长期目标是更好地理解 复杂的作用在调节丘脑活性中起着作用。主要目的是确定如何不同 GABA能和胆碱能突触输入的类型控制TRN神经元的输出。中心假设 指出GABA能和胆碱能的输入都可以有力地激发TRN神经元，并且特定类型 树枝状表达的电压和钙门控电导参与这些集成 输入。拟议研究的理由是了解GABA能的基础的机制 TRN中的胆碱能信号传导将有助于揭示TRN中网络活动的原理， 最终转化为对导致TRN功能障碍的特定过程的更好理解 与许多神经疾病有关。在强大的初步数据的指导下，中央假设 将通过三个特定目的测试：1）确定GABA能突触的功能特性 在TRN中的传输。在此目标下，TRN的GABA诱发激活的两种机制 神经元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。在此目标下，t-的贡献 将测试用于加工GABA能突触输入的钙和SK钾电导。 3）确定胆碱能输入到TRN的特性。在此目标下，动态激活的动力 通过在TRN中释放内源性乙酰胆碱，突触后烟碱和毒蕈碱受体将是 检查。这种方法将导致有关丘脑突触传播的新见解。这 拟议的研究很重要，因为它有望促进和扩展对如何截然不同的理解 突触输入形状在TRN中的网络活动。