Light-dependent induction of cFos during subjective day and night in PACAP-containing ganglion cells of the retinohypothalamic tract

Environmental light stimulation via the retinohypothalamic tract (RHT) is n ecessary for stable entrainment of circadian rhythms generated in the supra chiasmatic nucleus (SCN). In the current report, the authors characterized the functional activity and phenotype of retinal ganglion cells that give r ise to the RHT of the rat. Retinal ganglion cells that give rise to the RHT were identified by transsynaptic passage of an attenuated alpha herpesviru s known to have selective affinity for this pathway. Dual labeling immunocy tochemistry demonstrated co-localization of viral antigen and pituitary ade nylate cyclase activating polypeptide (PACAP) in retinal ganglion cells. Th is was confirmed using the anterograde tracer cholera toxin subunit B (ChB) . In normal and retinally degenerated monosodium glutamate (MSG)-treated ra ts, ChB co-localized with PACAP in axons of the retinorecipient zone of the SCN. Light-induced Fos-immunoreactivity (Fos-IR) was apparent in all PACAP -containing retinal ganglion cells and a population of non-PACAP-containing retinal ganglion cells at dawn of normal and MSG-treated animals. Within t he next 3 h, Fos disappeared in all non-PACAP-immunoreactive cells but pers isted in all PACAP-containing retinal ganglion cells until dusk. When anima ls were exposed to constant light, Fos-IR was sustained only in the PACAP-i mmunoreactive (PACAP-IR) retinal ganglion cells. Darkness eliminated Fos-IR in all PACAP-IR retinal ganglion cells, demonstrating that the induction o f Fos gene expression was light dependent. When animals were maintained in constant darkness and exposed to light pulses at ZT 14, ZT 19, or ZT 6, Fos -IR was induced in PACAP-IR retinal ganglion cells in a pattern similar to that seen at dawn. Collectively, these data indicate that PACAP is present in ganglion cells that give rise to the RHT and suggest a role for this pep tide in the light entrainment of the clock.