The lateral septum (LS) has been implicated in the regulation of locomotion. Nevertheless, the neurons synchronizing LS activity with the brain’s clock in the suprachiasmatic nucleus (SCN) remain unknown. By interrogating the molecular, anatomical and physiological heterogeneity of dopamine neurons of the periventricular nucleus (PeVN; A14 catecholaminergic group), we find that Th⁺/Dat1⁺ cells from its anterior subdivision innervate the LS in mice. These dopamine neurons receive dense neuropeptidergic innervation from the SCN. Reciprocal viral tracing in combination with optogenetic stimulation ex vivo identified somatostatin-containing neurons in the LS as preferred synaptic targets of extrahypothalamic A14 efferents. In vivo chemogenetic manipulation of anterior A14 neurons impacted locomotion. Moreover, chemogenetic inhibition of dopamine output from the anterior PeVN normalized amphetamine-induced hyperlocomotion, particularly during sedentary periods. Cumulatively, our findings identify a hypothalamic locus for the diurnal control of locomotion and pinpoint a midbrain-independent cellular target of psychostimulants.

外侧隔膜 (LS) 与运动的调节有关。然而，将 LS 活动与视交叉上核 (SCN) 中的大脑时钟同步的神经元仍然未知。通过询问脑室周围核多巴胺神经元（PeVN；A14 儿茶酚胺能组）的分子、解剖学和生理学异质性，我们发现Th ⁺ / Dat1 ⁺来自其前部细分的细胞支配小鼠的 LS。这些多巴胺神经元接受来自视交叉上核的密集神经肽能神经支配。相互病毒追踪与离体光遗传学刺激相结合，确定 LS 中含有生长抑素的神经元是下丘脑外 A14 传出神经元的首选突触目标。前 A14 神经元的体内化学遗传学操作影响运动。此外，前 PeVN 多巴胺输出的化学遗传抑制使苯丙胺诱导的过度运动正常化，特别是在久坐期间。总的来说，我们的研究结果确定了一个用于昼夜运动控制的下丘脑位点，并确定了一个独立于中脑的精神兴奋剂细胞靶点。