The role of the vLGN in non-image-forming visual behaviors and its underlying circuit organization

Abstract

Purpose : The mouse ventral lateral geniculate nucleus (vLGN) receives dense retinal ganglion cell (RGC) innervation but its role in vision remains unclear. We recently showed that the caudal vLGN segregates the visual input of RGCs that drive image-forming vision from the intrinsically photosensitive RGCs (ipRGCs) that drive non-image-forming behaviors. Here, in the context of this newly understood circuit organization, we investigate cell type-specific retina-to-vLGN pathways that drive and modulate non-image-forming behaviors (pupillary light response, circadian photoentrainment, and light-induced sleep).

Methods : Immunohistochemistry of cFos induction was paired with markers for vLGN cell types (Penk and Nos1) following circadian phase shifting light pulses (phase delay, ZT14, or phase advance, ZT22). We mapped afferents of vLGN Penk^Cre and Nos1^Cre cell types with Cre-dependent helper viruses and monosynaptic G-deleted rabies virus. We used viral chemogenetic strategies to silence (tetanus toxin) or activate (Gq DREADD) vLGN Penk^Cre cells to investigate their role in modulating non-image-forming visual behaviors.

Results : cFos induction in the vLGN increases in Penk cells in response to a ZT22 light pulse but not to a ZT14 light pulse compared to dark controls. Light-induced cFos in Nos1 cells is not time-dependent. Penk^Cre, but not Nos1^Cre, cells in the vLGN are post-synaptic to ipRGCs. Silencing/activating vLGN Penk^Cre, but not Nos1^Cre, cells causes an increase/decrease in pupil constriction during a light step. Preliminary results implicate vLGN Penk^Cre cells in phase advancement and sleep; silencing vLGN Penk^Cre cells results in deficits to phase advancing light shifts and activating vLGN Penk^Cre cells in the late night, but not the early night, induces sleep.

Conclusions : We find that Penk vLGN cells are light-responsive in a circadian time-dependent manner and receive exclusive ipRGC input, which are characteristics thought to be exclusive to the pacemaker, the suprachiasmatic nucleus. In contrast, vLGN Nos1 cells do not share these same features. In agreement with these findings, we show that vLGN Penk cells play a role in modulating non-image-forming visual behaviors. Penk cells modulate the pupillary light response during light steps and play a role in time-dependent visually responsive behaviors: light induced circadian phase advancement and sleep.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.