Formation and Maturation of Projections Between Thalamic Reticular Nucleus and Dorsal Lateral Geniculate Nucleus

项目摘要 用于研究丘脑回路发育的一个杰出模型是小鼠视觉 丘脑关于这个系统的大多数研究都集中在连接视网膜神经元的视网膜小神经通路上。 轴突与背外侧膝状体核（dLGN）的中继神经元。这些中继神经元将视觉信号 信息通过它们的轴突投射到初级视觉皮层，但这种投射也发送 丘脑网状核（TRN）的轴突侧支。TRN是一个GABA能核， 背侧丘脑，包括dLGN，是这些脑区的主要抑制性投射。因此，有一个 dLGN和TRN之间的反馈回路，这是已知的调解视觉注意，选择丘脑皮质 节奏，并参与多种疾病的过程。然而，当这个循环形成时， 目前尚不清楚发展情况。此外，不知道这些预测的发展是否 调节，像其他非视网膜投射到dLGN，视网膜信号。这些问题将在 三个具体目标：目标1将确定TRN终端何时到达dLGN，何时突触到达中继 神经元变得有功能，以及终端扩展和突触反应如何成熟; Aim 2将 通过dLGN研究TRN神经支配的类似参数，确定终端何时到达，何时到达， 突触的形成以及突触反应在早期发育过程中如何变化;目标3将比较 在存在和不存在视网膜输入的情况下，这些投射TRN和dLGN的发育时间过程 中央视觉结构，以确定是否视网膜终端协调的发展时间， 神经支配这些实验将利用转基因小鼠，这些小鼠特异性地标记来自 或者来自dLGN的那些。具体来说，GAD 65小鼠将用于可视化dLGN的TRN神经支配 同时将生长抑素-cre小鼠与通道视紫红质-2小鼠杂交， 在电生理记录中光活化TRN末端（目的1）。促肾上腺皮质激素释放激素 cre-重组酶小鼠将用于刺激和可视化dLGN向TRN的输入，并与 通道视紫红质-2小鼠或将用TdTomato标记该投射的Ai 9报告细胞系（aim 2）。 最后，在将所有这些小鼠杂交到数学5空背景中之后重复这些实验， 基因移除视网膜输入（目的3）。总之，这些实验将决定一个重要的 视觉系统的组成部分的发展，他们将测试的假设，视网膜终端在dLGN 协调非视网膜投射到dLGN的神经支配以及dLGN中继的轴突投射 神经元这些研究不仅将促进目前对视觉系统的理解， 对整个丘脑回路发育的影响。

Project Summary One of the preeminent models used to study the development of thalamic circuitry is the mouse visual thalamus. Most studies on this system have focused on the retinogeniculate pathway that connects retinal axons with relay neurons of the dorsal lateral geniculate nucleus (dLGN). These relay neurons transmit visual information to the visual cortex via their axonal projection to primary visual cortex but this projection also sends axon collaterals to the thalamic reticular nucleus (TRN). The TRN is a GABAergic nucleus that projects to the dorsal thalamus, including dLGN, and is the main inhibitory projection to these brain regions. Thus, there is a feedback loop between dLGN and TRN, which is known to mediate visual attention, select thalamocortical rhythms, and is involved in multiple diseases processes. However, when this loop is formed and how it develops is currently not known. Furthermore, it is unknown whether the development of these projections are regulated, like other nonretinal projections to dLGN, by retinal signaling. These questions will be addressed in three specific aims: Aim 1 will determine when TRN terminals arrive in dLGN, when synapses onto relay neurons become functional, and how both terminal expanse and synaptic responses mature; Aim 2 will investigate similar parameters for the innervation of TRN by dLGN, determining when terminals arrive, when synapses are made and how synaptic responses change over early development; Aim 3 will compare the developmental time course of these projections TRN and dLGN in the presence and absence of retinal input to central visual structures in order to determine if retinal terminals coordinate the developmental timing of innervation. These experiments will utilize transgenic mice that specifically label either the projections from TRN or those from dLGN. Specifically, the GAD65 mouse will be used to visualize TRN innervation of dLGN with EGFP while the somatostatin-cre mouse will be crossed to a channelrhodopsin-2 mouse in order to photoactivate TRN terminals in electrophysiological recordings (aim 1). The corticotropin releasing hormone cre-recombinase mouse will be used to both stimulate and visualize dLGN inputs to TRN with crosses to either the channelrhodopsin-2 mouse or an Ai9 reporter line that will label this projection with TdTomato (aim 2). Finally, these experiments will be repeated after crossing all these mice into a math 5 null background to genetically remove retinal inputs (aim 3). Together, these experiments will determine how an important component of the visual system develops and they will test the hypothesis that retinal terminals in dLGN coordinate the innervation of non-retinal projections to dLGN as well as the axonal projections of dLGN relay neurons. These studies will not only advance the current understanding of the visual system but will have implications for circuit development in the thalamus as a whole.