Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Neuroscience, Brown University, Providence, RI 02912-1978, USA.
Brown Institute for Brain Science, Brown University, Providence, RI 02912-1978, USA; Department of Neuroscience, Brown University, Providence, RI 02912-1978, USA.
Neuroscience. 2018 Jan 1;368:187-198. doi: 10.1016/j.neuroscience.2017.09.038. Epub 2017 Sep 28.
The thalamic reticular nucleus (TRN) is optimally positioned to regulate information processing and state dynamics in dorsal thalamus. Distinct inputs depolarize TRN on multiple time scales, including thalamocortical afferents, corticothalamic 'feedback', and neuromodulation. Here, we systematically tested the concurrent and after-effects of depolarization duration on TRN firing in vivo using selective optogenetic drive. In VGAT-ChR2 mice, we isolated TRN single units (SU: N = 100 neurons) that responded at brief latency (≤5 ms) to stimulation. These units, and multi-unit activity (MUA) on corresponding electrodes, were analyzed in detail. Consistent with prior findings in relay neurons, after light cessation, burst-like events occurred in 74% of MUA sites, and 16% of SU. Increasing optical duration from 2 to 330 ms enhanced this burst probability, and decreased the latency to the first burst after stimulation. During stimulation, neurons demonstrated a 'plateau' firing response lasting 20-30 ms in response to light, but significant heterogeneity existed in the minimal stimuli required to drive this response. Two distinct types were evident, more sensitive 'non-linear' neurons that were driven to the plateau response by 2 or 5 ms pulses, versus 'linear' neurons that fired proportionally to optical duration, and reached the plateau with ∼20-ms optical drive. Non-linear neurons showed higher evoked firing rates and burst probability, but spontaneous rate did not differ between types. These findings provide direct predictions for TRN responses to a range of natural depolarizing inputs, and a guide for the optical control of this key structure in studies of network function and behavior.
丘脑网状核(TRN)位于最佳位置,可调节背侧丘脑的信息处理和状态动力学。包括丘脑皮质传入、皮质丘脑“反馈”和神经调制在内的不同输入可在多个时间尺度上使 TRN 去极化。在这里,我们使用选择性光遗传学驱动,在体内系统地测试了去极化持续时间对 TRN 放电的并发和后效。在 VGAT-ChR2 小鼠中,我们分离出对刺激有短潜伏期(≤5ms)反应的 TRN 单个单位(SU:N=100 个神经元)。详细分析了这些单位和相应电极上的多单位活动(MUA)。与中继神经元中的先前发现一致,在光停止后,74%的 MUA 位点和 16%的 SU 会发生爆发样事件。将光持续时间从 2 毫秒增加到 330 毫秒增强了这种爆发概率,并减少了刺激后的第一个爆发的潜伏期。在刺激期间,神经元表现出持续 20-30ms 的“平台”发射反应,对光反应,但驱动这种反应所需的最小刺激存在显著的异质性。两种不同的类型是明显的,更敏感的“非线性”神经元可以通过 2 或 5ms 的脉冲驱动到平台反应,而“线性”神经元与光持续时间成比例发射,并通过约 20ms 的光驱动达到平台。非线性神经元显示出更高的诱发发射率和爆发概率,但两种类型之间的自发发射率没有差异。这些发现为 TRN 对一系列自然去极化输入的反应提供了直接预测,并为研究网络功能和行为中该关键结构的光控提供了指导。