Superior Colliculus Controls the Activity of the Rostromedial Tegmental Nuclei in an Asymmetrical Manner

Dopaminergic (DA) neurons of the midbrain are involved in controlling orienting and approach of animals toward relevant external stimuli. The firing of DA neurons is regulated by many brain structures; however, the sensory input is provided predominantly by the ipsilateral superior colliculus (SC). It is suggested that SC also innervates the contralateral rostromedial tegmental nucleus (RMTg)-the main inhibitory input to DA neurons. Therefore, this study aimed to describe the physiology and anatomy of the SC-RMTg pathway. To investigate the anatomic connections within the circuit of interest, anterograde, retrograde, and transsynaptic tract-tracing studies were performed on male Sprague Dawley rats. We have observed that RMTg is monosynaptically innervated predominantly by the lateral parts of the intermediate layer of the contralateral SC. To study the physiology of this neuronal pathway, we conducted in vivo electrophysiological experiments combined with optogenetics; the activity of RMTg neurons was recorded using silicon probes, while either contralateral or ipsilateral SC was optogenetically stimulated. Obtained results revealed that activation of the contralateral SC excites the majority of RMTg neurons, while stimulation of the ipsilateral SC evokes similar proportions of excitatory or inhibitory responses. Consequently, single unit recordings showed that the activation of RMTg neurons innervated by the contralateral SC, or stimulation of contralateral SC-originating axon terminals within the RMTg, inhibits midbrain DA neurons. Together, the anatomy and physiology of the discovered brain circuit suggest its involvement in the orienting and motivation-driven locomotion of animals based on the direction of external sensory stimuli.