Synaptic Integration in Neurons of the Thalamic Reticular Nucleus

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起着关键作用 处理，在丘脑皮质网络中产生同步振荡，以及在调节注意力。 TRN神经元被起源于皮质和丘脑的谷氨酸能输入迅速激活。反过来, 它们与丘脑背侧核中的几个中继细胞形成强大的抑制性联系。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 它们起源于脑干和基底前脑。这项提议的长期目标是更好地理解 TRN在调节丘脑活动中扮演的复杂角色。主要目标是确定有多明显 GABA能和胆碱能突触输入控制TRN神经元的输出。中心假说 声称GABA能和胆碱能都能强烈地兴奋TRN神经元，并且特定类型的 树突表达的电压和钙门控电导参与了这些信号的整合 投入。这项拟议研究的基本原理是，理解GABA能的机制 TRN中的胆碱能信号将有助于揭示TRN中潜在的网络活动的原理， 最终转化为更好地理解导致TRN功能障碍的具体过程 与许多神经疾病有关。在强劲的初步数据指导下，中心假设 将通过三个特定的目的进行测试：1)确定GABA能突触的功能特性 在TRN中的传输。在这一目标下，GABA诱导TRN激活的两种机制 本课程将研究神经元及其对中继细胞活动的功能影响。2)确定 树枝状电压和钙激活电导的功能作用。在这一目标下，T-T的贡献 将测试处理GABA能突触输入的类型钙和SK钾电导。 3)确定TRN的胆碱能输入的性质。在这一目标下，激活的动力学基础 突触后烟碱和毒扁豆碱受体将由内源性乙酰胆碱在TRN中释放 检查过了。这一方法将导致对丘脑突触传递的新见解。这个 提出的研究具有重要意义，因为它有望促进和扩大对如何区分 突触输入塑造了TRN的网络活动。

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.