Abstract
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 processing 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 multielectrode array recordings of SNc and VTA neuronal activity combined with optogenetic stimulation of either 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 connection, especially within the SNc. Ex vivo recordings also confirmed that this lateralized pathway is direct. The described features of the SC to 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.
Significance statement The direction of animals' behavior is a manifestation of asymmetry in dopamine (DA) release between the left and right striatum – unilateral activation of DA neurons biases movement towards the contralateral side. Our study demonstrates that such activation is induced by the ipsilateral superior colliculus (SC), which processes sensory information from the contralateral body side. Notably, our previous findings indicate that the SC innervates and activates the rostromedial tegmental nucleus, a primary inhibitory input to the DA system, albeit in the contralateral hemisphere. Thus, our research describes a SC-originating neuronal circuit that directly enhances the activity of ipsilateral DA neurons while simultaneously diminishing the activity of contralateral DA neurons, thereby amplifying the imbalance in DA release between the hemispheres.
Footnotes
The authors declare no competing financial interests.
This work has been supported by the Polish National Science Center grants: 2017/27/N/NZ4/00785 and 2020/36/T/NZ4/00341 awarded to KP, 2018/28/C/NZ4/00099 awarded to ŁC, 2019/33/B/NZ4/03127 awarded to TB, and the statutory funds of the Institute of Zoology and Biomedical Research, Jagiellonian University. The open-access publication of this article was funded by the Priority Research Area BioS under the program “Excellence Initiative – Research University” at the Jagiellonian University in Krakow.