Superior Colliculus Controls the Activity of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in an Asymmetrical Manner

Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) play a crucial role in controlling animals' orienting and approach behaviors toward relevant environmental stimuli. The ventral midbrain receives sensory input from the superior colliculus (SC), a tectal region that processes information from contralateral receptive fields of various modalities. Given the significant influence of dopamine release imbalance in the left and right striatum on animals' movement direction, our study aimed to investigate the lateralization of the connection between the lateral SC and the midbrain DA system in male rats. We explored the circuit's anatomy using transsynaptic viral tract-tracing and its physiology using in vivo single-unit and ex vivo multi-electrode array recordings of SNc and VTA neuronal activity combined with optogenetic stimulation of either the ipsilateral or contralateral SC or its terminals. During the experiments, DA neurons were identified optogenetically (in vivo recordings) or pharmacologically (ex vivo recordings). Anatomical findings revealed a bilateral innervation pattern of the lateral SC to the ventral midbrain, with a significantly stronger ipsilateral connection, particularly evident in the SNc, involving both DA and non-DA neurons. This anatomical asymmetry was also expressed during in vivo and ex vivo recordings, which showed a predominance of ipsilateral connections, especially within the SNc. Ex vivo recordings also confirmed that this lateralized pathway is direct. The described features of the SC→VTA/SNc neuronal circuit, particularly its anatomical and physiological asymmetry, suggest its involvement in orienting and approach behaviors guided by the direction of incoming sensory stimuli.