Ahrens Sandra, Jaramillo Santiago, Yu Kai, Ghosh Sanchari, Hwang Ga-Ram, Paik Raehum, Lai Cary, He Miao, Huang Z Josh, Li Bo
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Indiana University, Bloomington, Indiana, USA.
Nat Neurosci. 2015 Jan;18(1):104-11. doi: 10.1038/nn.3897. Epub 2014 Dec 15.
Selective processing of behaviorally relevant sensory inputs against irrelevant ones is a fundamental cognitive function whose impairment has been implicated in major psychiatric disorders. It is known that the thalamic reticular nucleus (TRN) gates sensory information en route to the cortex, but the underlying mechanisms remain unclear. Here we show in mice that deficiency of the Erbb4 gene in somatostatin-expressing TRN neurons markedly alters behaviors that are dependent on sensory selection. Whereas the performance of the Erbb4-deficient mice in identifying targets from distractors was improved, their ability to switch attention between conflicting sensory cues was impaired. These behavioral changes were mediated by an enhanced cortical drive onto the TRN that promotes the TRN-mediated cortical feedback inhibition of thalamic neurons. Our results uncover a previously unknown role of ErbB4 in regulating cortico-TRN-thalamic circuit function. We propose that ErbB4 sets the sensitivity of the TRN to cortical inputs at levels that can support sensory selection while allowing behavioral flexibility.
对行为相关的感觉输入与无关输入进行选择性处理是一种基本的认知功能，其受损与主要精神疾病有关。已知丘脑网状核（TRN）在感觉信息传向皮层的途中起闸门作用，但其潜在机制仍不清楚。在此，我们在小鼠中发现，表达生长抑素的TRN神经元中Erbb4基因的缺失显著改变了依赖感觉选择的行为。虽然Erbb4基因缺陷小鼠从干扰物中识别目标的能力有所提高，但其在相互冲突的感觉线索之间切换注意力的能力受损。这些行为变化是由增强的皮层对TRN的驱动介导的，这种驱动促进了TRN介导的对丘脑神经元的皮层反馈抑制。我们的结果揭示了ErbB4在调节皮质-TRN-丘脑回路功能方面以前未知的作用。我们提出，ErbB4将TRN对皮层输入的敏感性设定在能够支持感觉选择同时允许行为灵活性的水平。
