Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Nat Neurosci. 2022 Feb;25(2):140-153. doi: 10.1038/s41593-021-00996-1. Epub 2022 Jan 31.
The thalamus engages in various functions including sensory processing, attention, decision making and memory. Classically, this diversity of function has been attributed to the nuclear organization of the thalamus, with each nucleus performing a well-defined function. Here, we highlight recent studies that used state-of-the-art expression profiling, which have revealed gene expression gradients at the single-cell level within and across thalamic nuclei. These gradients, combined with anatomical tracing and physiological analyses, point to previously unappreciated heterogeneity and redefine thalamic units of function on the basis of unique input-output connectivity patterns and gene expression. We propose that thalamic subnetworks, defined by the intersection of genetics, connectivity and computation, provide a more appropriate level of functional description; this notion is supported by behavioral phenotypes resulting from appropriately tailored perturbations. We provide several examples of thalamic subnetworks and suggest how this new perspective may both propel progress in basic neuroscience and reveal unique targets with therapeutic potential.
丘脑参与多种功能,包括感觉处理、注意力、决策和记忆。传统上,这种功能的多样性归因于丘脑的核组织,每个核都执行着明确的功能。在这里,我们强调了最近的一些研究,这些研究使用了最先进的表达谱分析,揭示了单个核内和核间的单细胞水平的基因表达梯度。这些梯度,结合解剖追踪和生理分析,指出了以前未被认识到的异质性,并根据独特的输入-输出连接模式和基因表达重新定义了丘脑的功能单位。我们提出,由遗传、连接和计算的交集定义的丘脑子网为功能描述提供了更合适的层次;这一概念得到了适当调整的干扰导致的行为表型的支持。我们提供了几个丘脑子网的例子,并提出了这种新观点如何既能推动基础神经科学的进展,又能揭示具有治疗潜力的独特靶点。