A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice

Area of Science:

• Neuroscience
• Chronobiology
• Neuropharmacology

Background:

• The lateral septum (LS) plays a role in locomotion control.
• The specific neurons linking the suprachiasmatic nucleus (SCN) clock to LS activity remain unidentified.
• Dopamine neurons in the periventricular nucleus (PeVN) are potential candidates.

Purpose of the Study:

• To identify and characterize the neurons that synchronize LS activity with the SCN clock.
• To investigate the role of these neurons in locomotion and psychostimulant effects.

Main Methods:

• Molecular, anatomical, and physiological characterization of anterior PeVN (A14) dopamine neurons in mice.
• Viral tracing and optogenetic stimulation to map neural connections.
• In vivo chemogenetic manipulation to assess functional impact on locomotion.

Main Results:

• Anterior PeVN dopamine neurons (Th+/Dat1+) innervate the LS and receive input from the SCN.
• Somatostatin-containing neurons in the LS are primary targets of these dopamine neurons.
• Manipulation of anterior A14 neurons altered locomotion; inhibition normalized amphetamine-induced hyperlocomotion.

Conclusions:

• Identified a hypothalamic pathway for diurnal locomotion control involving anterior PeVN dopamine neurons projecting to the LS.
• Pinpointed a midbrain-independent cellular target for psychostimulant action.