Precise Coordination of 3-dimensional Rotational Kinematics by Ventral Tegmental Area GABAergic Neurons

Abstract

The Ventral Tegmental Area (VTA) is a midbrain region implicated in a variety of motivated behaviors. However, the function of VTA GABAergic (Vgat+) neurons remains poorly understood. Here, using 3D motion capture, in vivo electrophysiology and calcium imaging, and optogenetics, we demonstrate a novel function of VTA Vgat+ neurons. We found 5 three distinct populations of neurons, each representing head angle about a principal axis of rotation: pitch, roll, and yaw. For each axis, opponent cell groups were found that increase firing when the head moves in one direction, and decrease firing in the opposite direction. Selective excitation and inhibition of VTA Vgat+ neurons generate opposite rotational movements. The relationship between these neurons and head angle is degraded only at the time of reward 10 consumption, at which point all head-angle related neuronal subpopulations show indistinguishable reward-related responses. Thus, VTA Vgat+ neurons serve a critical role in the control of rotational kinematics while pursuing a moving target. This general-purpose steering function can guide animals toward desired spatial targets in any motivated behavior. 15 20 25 30 3

Ventral Tegmental Dopamine Neurons Control the Impulse Vector during Motivated Behavior

“…Instead, the effect of VTA DA neurons depends on the motivational context. This could explain why others have not been able to elicit movement by mimicking phasic DA activity [28]. This observation is in accord with the idea that DA, as a neuromodulator, primarily adjusts the gain of striatal medium spiny projection neurons [37].…”

“…We next tested the effects of optogenetic inhibition on VTA DA neurons. We injected Cre-dependent soma-targeted Guillardia theta anion-conducting channelrhodopsin (stGtACR2), which has been shown to effectively shut down neural activity with high temporal precision [28][29][30], into the VTA of DAT-Ires-Cre (DAT::StGtACR2 VTA , n = 4) or of WT (WT::StGtACR2 VTA , n = 5) mice for controls (Figure 6G). We also confirmed potent optogenetic silencing of DAT::StGtACR2 VTA neurons using in vitro whole-cell patch-clamp recording in acutely prepared brain slices (Figures 6H and S6), demonstrating for the first time robust inhibition of DA neurons with this newly developed opsin.…”

“…It has recently been reported that VTA GABA neurons, which are directly connected with DA neurons, can represent and command head angles around orthogonal axes of rotation [28]. Given the interaction between VTA GABA and DA, DA could contribute to head angle commands by providing the requisite amount of torque necessary to achieve a change in head position (i.e., angular velocity) in order to move toward or away from motivationally relevant stimuli.…”

Activation of VTA GABA neurons disrupts reward seeking by altering temporal processing

“…In contrast, we recently demonstrated that VTA GABA activation greatly attenuates reward seeking in an operant task heavily dependent on cue responding, while chemogenetic activation of the VTA GABA terminals in the NAc had no effect [34]. Other studies have shown that VTA GABA activation promotes sleep [35] and head orienting towards desired spatial targets [36]. Thus, it is becoming clear that VTA GABA neurons contribute to the regulation and control of a myriad of motivated behaviors.…”