Glutamatergic Septal Inputs to VTA Modulate Movement Onset and Speed
1 Neuronal Networks Group, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
2 Department of Cellular Neuroscience, Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany
The Ventral Tegmental Area (VTA) neurons are classically studied for their function in reward, addiction and goal-directed behavior. Recent studies are also pointing to a role of VTA during locomotion: VTA neurons are active at movement onset, fire during movement, and send inputs to the dorsal striatum in an acceleration-dependent pattern. On the other side, locomotion onset and speed are controlled by the glutamatergic (VGluT2+) population of the Medial Septum/Diagonal Band of Broca (MSDB). When optogenetically stimulated, these neurons initiate locomotion and modulate the animal’s speed in a frequency-dependent manner. However, the MSDB has no direct projections to any motor-related area. It stands to reason, that MSDB VGluT2+ neurons could send inputs to VTA, which in turn projects to the brain areas responsible for movement execution.
A multidisciplinary approach including slice electrophysiology, in vivo fiberphotometry, and optogenetics was used to test if MSDB VGluT2+ inputs to VTA play a role during locomotion. Preliminary in vivo results show that optogenetic activation of VGluT2+ MSDB projections in VTA is sufficient to induce locomotion onset and to control the speed in a frequency-dependent manner. These findings are supported by the increase in calcium signal of the VGluT2+ MSDB axons in VTA when the animal moves spontaneously. In vitro patch-clamp data confirmed the existence of a monosynaptic glutamatergic connection between MSDB and VTA and highlighted how VGluT2+ MSDB inputs preferentially target VGluT2+ VTA neurons. Finally, in vivo optogenetic stimulation of VTA VGluT2+ neurons reliably induced locomotion, recapitulating the effect of MSDB VGluT2+ axon stimulation.