Jennings Joshua H, Ung Randall L, Resendez Shanna L, Stamatakis Alice M, Taylor Johnathon G, Huang Jonathan, Veleta Katie, Kantak Pranish A, Aita Megumi, Shilling-Scrivo Kelson, Ramakrishnan Charu, Deisseroth Karl, Otte Stephani, Stuber Garret D
Departments of Psychiatry and Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Neurobiology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Departments of Psychiatry and Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Cell. 2015 Jan 29;160(3):516-27. doi: 10.1016/j.cell.2014.12.026.
Optimally orchestrating complex behavioral states, such as the pursuit and consumption of food, is critical for an organism's survival. The lateral hypothalamus (LH) is a neuroanatomical region essential for appetitive and consummatory behaviors, but whether individual neurons within the LH differentially contribute to these interconnected processes is unknown. Here, we show that selective optogenetic stimulation of a molecularly defined subset of LH GABAergic (Vgat-expressing) neurons enhances both appetitive and consummatory behaviors, whereas genetic ablation of these neurons reduced these phenotypes. Furthermore, this targeted LH subpopulation is distinct from cells containing the feeding-related neuropeptides, melanin-concentrating hormone (MCH), and orexin (Orx). Employing in vivo calcium imaging in freely behaving mice to record activity dynamics from hundreds of cells, we identified individual LH GABAergic neurons that preferentially encode aspects of either appetitive or consummatory behaviors, but rarely both. These tightly regulated, yet highly intertwined, behavioral processes are thus dissociable at the cellular level.
最佳地协调复杂的行为状态,如对食物的追逐和摄取,对生物体的生存至关重要。外侧下丘脑(LH)是对食欲和进食行为至关重要的神经解剖区域,但LH内的单个神经元是否对这些相互关联的过程有不同贡献尚不清楚。在这里,我们表明,对分子定义的LH GABA能(表达Vgat)神经元子集进行选择性光遗传学刺激可增强食欲和进食行为,而这些神经元的基因消融则会降低这些表型。此外,这个靶向的LH亚群与含有与进食相关的神经肽、促黑素细胞激素(MCH)和食欲素(Orx)的细胞不同。利用自由活动小鼠的体内钙成像来记录数百个细胞的活动动态,我们鉴定出了单个LH GABA能神经元,它们优先编码食欲或进食行为的某些方面,但很少同时编码两者。因此,这些受到严格调节但高度交织的行为过程在细胞水平上是可分离的。