Extended Data Fig. 10: Circuit mechanism of contra lSC excitation, and model of exploration via iSPNs-Colliculus.

a-d. Potential circuit mechanisms by which iSPN could excite contra lSC. Color indicates the direction of modulation after iSPN activation, and shapes indicates cell type (triangle: excitatory; circle: inhibitory). Note that all these mechanisms are not mutually exclusive and a combination of these might occur together. We provide evidence for model a and b, in which inhibition lSC in one hemisphere disinhibit lSC on the opposite hemisphere (Fig. 3). a. Long-range inhibitory projection crossing the midline could mediate contra lSC excitation. In this scenario, iSPN will cause SNr to be excited, suppressing ipsi lSC, which in turn will disinhibit contra lSC. b. Long-range excitatory projection innervating local inhibitory interneurons could mediate this effect. c. A region outside SC (grey patch) could mediate the disinhibitory effect (e.g. nucleus isthmus; see main text). d. Separate population of SNr neurons could innervate ipsi and contra lSC. In this scenario, iSPN activation would lead to bidirectional modulation of SNr neurons, with ipsi lSC projecting SNr neurons being excited, and contra lSC projecting SNr neurons being inhibited. e. Schematic diagram of the exploration model proposed. iSPN integrate information about the outcome of specific action performed in a specific context. The function of iSPN to learn which actions lead to a negative outcome and suppress them in the future. iSPN can then suppress the target action that lead to the negative outcome. Via disinhibition within SC, this leads to a rapid execution of a competing motor program. Although the circuit from specific iSPN to target action is hardwired, competitive interaction within SC is more dynamic and tunable so the same activation of iSPN can lead to different actions depending on the availability of the competing motor program.