Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
NIH-Johns Hopkins University Graduate Partnership Program, Baltimore, MD, USA.
Nat Commun. 2021 May 14;12(1):2811. doi: 10.1038/s41467-021-23040-z.
The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.
上乳突区（SuM）是下丘脑的一个后部结构，已知其调节海马θ振荡和觉醒。然而，最近的研究报告称，用神经活性化学物质刺激 SuM 神经元，包括滥用物质，具有强化作用。我们进行了实验以阐明 SuM 神经元如何介导这种作用。使用光遗传学，我们发现 SuM 谷氨酸能（GLU）神经元的兴奋在小鼠中具有强化作用；这种作用是通过它们投射到隔核 GLU 神经元来传递的。SuM 神经元在探索和接近行为期间活跃，并在蔗糖消耗期间减少活动。一致地，抑制 SuM 神经元会破坏接近反应，但不会破坏蔗糖消耗。这些功能类似于中脑边缘多巴胺神经元的功能。事实上，SuM 到隔核 GLU 神经元和隔核到腹侧被盖区（VTA）GLU 神经元的刺激激活了中脑边缘多巴胺神经元。我们提出，上乳突-隔核-VTA 通路调节唤醒，从而强化和激发与环境的行为相互作用。
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