A septal-ventral tegmental area circuit drives exploratory behavior.

To survive, animals need to balance their exploratory drive with their need for safety. Subcortical circuits play an important role in initiating and modulating movement based on external demands and the internal state of the animal; however, how motivation and onset of locomotion are regulated remain largely unresolved. Here, we show that a glutamatergic pathway from the medial septum and diagonal band of Broca (MSDB) to the ventral tegmental area (VTA) controls exploratory locomotor behavior in mice. Using a self-supervised machine learning approach, we found an overrepresentation of exploratory actions, such as sniffing, whisking, and rearing, when this projection is optogenetically activated. Mechanistically, this role relies on glutamatergic MSDB projections that monosynaptically target a subset of both glutamatergic and dopaminergic VTA neurons. Taken together, we identified a glutamatergic basal forebrain to midbrain circuit that initiates locomotor activity and contributes to the expression of exploration-associated behavior.

Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex.

Reward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. Yet, it is unknown, how the VTA influences cortical frequency processing and spectral integration. Therefore, we investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils. While auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects persisted over more than 30 minutes after VTA stimulation. Altogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. We thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.