Retinal input integration in excitatory and inhibitory neurons in the mouse superior colliculus in vivo

The superior colliculus (SC) is a midbrain structure that contains one of the highest densities of inhibitory neurons in the brain and, together with the thalamocortical visual system, it plays a key role in visually guided behaviors. The SC receives direct inputs from retinal ganglion cells (RGCs) but whether excitatory and inhibitory SC neurons differentially integrate retinal activity in vivo is still largely unknown. We recently established an extracellular recording approach using high-density electrodes to measure the activity of RGCs simultaneously with their postsynaptic SC targets in vivo, that allows addressing how SC neurons integrate RGC activity. Here, we employ this method to study the functional properties and dynamics that govern retinocollicular signaling in a cell-type specific manner by identifying GABAergic SC neurons using optotagging in anesthetized VGAT- ChR2 mice. We measured 305 monosynaptically connected RGC-SC pairs, out of which approximately one third of retinal afferents connect onto inhibitory SC neurons. We show that both excitatory and inhibitory SC neurons receive comparably strong RGC inputs, with functionally similar RGC-SC pairs showing stronger connections. Our results demonstrate that similar wiring rules apply for RGCs innervation of both excitatory and inhibitory SC neurons, which is unlike the cell-type specific connectivity in the thalamocortical system. Contrasting the similar RGC-SC connection strength, we observed that RGC activity contributed more to the activity of postsynaptic excitatory SC neurons than to the activity of postsynaptic inhibitory SC neurons. This implies that the excitatory SC neurons are more specifically coupled to RGC afferent inputs, while inhibitory SC neurons may integrate additional inputs from other sources. Taken together, our study deepens the understanding of cell-type specific retinocollicular functional connectivity and emphasizes that the two major brain areas for visual processing, the visual cortex and the superior colliculus, differently integrate sensory afferent inputs.