A role for thalamic projection GABAergic neurons in circadian responses to light

Brock, O.; Gelegen, C. E.; Salgarella, I.; Sully, P.; Jager, P.; Menage, L.; Mehta, I.; Jeczmien-Lazur, J.; Djama, D.; Strother, L.; Coculla, A.; Vernon, A. C.; Brickley, S.; Holland, P.; Cooke, S.; Delogu, A.

doi:10.1101/2022.02.24.481804

bioRxiv · 10.1101/2022.02.24.481804

A role for thalamic projection GABAergic neurons in circadian responses to light

Brock, O.·Gelegen, C. E.·Salgarella, I.·Sully, P.·Jager, P.·Menage, L.·Mehta, I.·Jeczmien-Lazur, J.·Djama, D.·Strother, L.·Coculla, A.·Vernon, A. C.·Brickley, S.·Holland, P.·Cooke, S.·Delogu, A.

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Abstract

The thalamus is an important hub for sensory information and participates in sensory perception, regulation of attention, arousal and sleep. These functions are executed primarily by glutamatergic thalamocortical neurons that extend axons to the cortex and initiate cortico-thalamocortical connectional loops. However, the thalamus also contains projection GABAergic neurons that do not engage in direct communication with the cortex. Here, we have harnessed recent insight into the development of the intergeniculate (IGL), the ventrolateral geniculate (LGv) and the perihabenula (pHB) to specifically target and manipulate thalamic projection GABAergic neurons in female and male mice. Our results show that thalamic GABAergic neurons of the IGL and LGv receive retinal input from diverse classes of ipRGCs, but not from the M1 ipRGC type, while those in the pHB lack direct retinal input. We describe the synergistic role of the photoreceptor melanopsin and the thalamic neurons of the IGL/LGv in circadian entrainment to dim light. We identify a requirement for the thalamic IGL/LGv in the rapid changes in vigilance states associated with circadian light transitions. Furthermore, we map a previously undescribed thalamic network of developmentally related GABAergic neurons in the IGL/LGv complex and the pHB potentially involved in light-dependent mood regulation. Significance statementThe intergeniculate leaflet and ventral geniculate nucleus are part of the extended circadian system and mediate some non-image-forming visual functions. Here we show that each of these structures has a thalamic (dorsal) as well as prethalamic (ventral) developmental origin. We map the retinal input to thalamus-derived cells in the IGL/LGv complex and discover that while ipRGC input is dominant, this is not likely to originate from M1-ipRGCs. We describe the extent of similarity in synaptic input to developmentally related cells in the IGL/LGv and in the perihabenula nucleus (pHB). We implicate thalamic cells in the IGL/LGv in vigilance state transitions at circadian light changes and in overt behavioural entrainment to dim light, the latter exacerbated by concomitant loss of melanopsin expression.

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Brock, O., Gelegen, C. E., Salgarella, I., Sully, P., Jager, P., Menage, L., Mehta, I., Jeczmien-Lazur, J., Djama, D., Strother, L., Coculla, A., Vernon, A. C., Brickley, S., Holland, P., Cooke, S., Delogu, A.. 2022-02-25. A role for thalamic projection GABAergic neurons in circadian responses to light. https://doi.org/10.1101/2022.02.24.481804

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