Genetically Defined Functional Modules for Spatial Orienting in the Mouse Superior Colliculus

In order to explore and interact with their surroundings, animals need to orient toward specific positions in space. Throughout the animal kingdom, head movements represent a primary form of orienting behavior. The superior colliculus (SC) is a fundamental structure for the generation of orienting responses, but how genetically distinct groups of collicular neurons contribute to these spatially tuned behaviors remains largely to be defined. Here, through the genetic dissection of the murine SC, we identify a functionally and genetically homogeneous subclass of glutamatergic neurons defined by the expression of the paired-like homeodomain transcription factor Pitx2. We show that the optogenetic stimulation of Pitx2(ON) neurons drives three-dimensional head displacements characterized by stepwise, saccade-like kinematics. Furthermore, during naturalistic foraging behavior, the activity of Pitx2(ON) neurons precedes and predicts the onset of spatially tuned head movements. Intriguingly, we reveal that Pitx2(ON) neurons are clustered in an orderly array of anatomical modules that tile the entire intermediate layer of the SC. Such a modular organization gives origin to a discrete and discontinuous representation of the motor space, with each Pitx2(ON) module subtending a defined portion of the animal’s egocentric space. The modularity of Pitx2(ON) neurons provides an anatomical substrate for the convergence of spatially coherent sensory and motor signals of cortical and subcortical origins, thereby promoting the recruitment of appropriate movement vectors. Overall, these data support the view of the superior colliculus as a selectively addressable and modularly organized spatial-motor register.