Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, United States of America.
Department of Internal Medicine, Pharmacology and Toxicology Unit, University of Genoa, Genoa, Italy.
PLoS One. 2018 Jun 12;13(6):e0198991. doi: 10.1371/journal.pone.0198991. eCollection 2018.
Cracking the cytoarchitectural organization, activity patterns, and neurotransmitter nature of genetically-distinct cell types in the lateral hypothalamus (LH) is fundamental to develop a mechanistic understanding of how activity dynamics within this brain region are generated and operate together through synaptic connections to regulate circuit function. However, the precise mechanisms through which LH circuits orchestrate such dynamics have remained elusive due to the heterogeneity of the intermingled and functionally distinct cell types in this brain region. Here we reveal that a cell type in the mouse LH identified by the expression of the calcium-binding protein parvalbumin (PVALB; LHPV) is fast-spiking, releases the excitatory neurotransmitter glutamate, and sends long range projections throughout the brain. Thus, our findings challenge long-standing concepts that define neurons with a fast-spiking phenotype as exclusively GABAergic. Furthermore, we provide for the first time a detailed characterization of the electrophysiological properties of these neurons. Our work identifies LHPV neurons as a novel functional component within the LH glutamatergic circuitry.
破解外侧下丘脑 (LH) 中遗传上不同细胞类型的细胞结构组织、活动模式和神经递质性质,对于理解该脑区的活动动态是如何产生的以及如何通过突触连接共同运作来调节回路功能至关重要。然而,由于该脑区中混杂和功能不同的细胞类型的异质性,LH 回路协调这种动态的精确机制仍然难以捉摸。在这里,我们揭示了一种在小鼠 LH 中通过钙结合蛋白 parvalbumin (PVALB; LHPV) 的表达来识别的细胞类型,其特征是快速放电、释放兴奋性神经递质谷氨酸,并在整个大脑中发出长程投射。因此,我们的发现挑战了长期以来将具有快速放电表型的神经元定义为仅 GABA 能神经元的概念。此外,我们首次提供了这些神经元电生理特性的详细特征。我们的工作将 LHPV 神经元鉴定为 LH 谷氨酸能回路中的一个新的功能组成部分。