A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice

Solomiia Korchynska, Patrick Rebernik, Marko Pende, Laura Boi, Alán Alpár, Ramon Tasan, Klaus Becker, Kira Balueva, Saiedeh Saghafi, Peer Wulff, Tamas L. Horvath, Gilberto Fisone, Hans-Ulrich Dodt, Tomas Hökfelt, Tibor Harkany () and Roman A. Romanov ()
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Solomiia Korchynska: Medical University of Vienna
Patrick Rebernik: Medical University of Vienna
Marko Pende: Medical University of Vienna
Laura Boi: Karolinska Institutet
Alán Alpár: Semmelweis University
Ramon Tasan: Medical University Innsbruck
Klaus Becker: Medical University of Vienna
Kira Balueva: Christian-Albrechts-University
Saiedeh Saghafi: Technical University of Vienna
Peer Wulff: Christian-Albrechts-University
Tamas L. Horvath: Yale School of Medicine
Gilberto Fisone: Karolinska Institutet
Hans-Ulrich Dodt: Medical University of Vienna
Tomas Hökfelt: Karolinska Institutet
Tibor Harkany: Medical University of Vienna
Roman A. Romanov: Medical University of Vienna

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-33584-3

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