Light-arousal and circadian photoreception circuits intersect at the large PDF cells of the Drosophila brain

Abstract

The neural circuits that regulate sleep and arousal as well as their integration with circadian circuits remain unclear, especially in Drosophila. This issue intersects with that of photoreception, because light is both an arousal signal in diurnal animals and an entraining signal for the circadian clock. To identify neurons and circuits relevant to light-mediated arousal as well as circadian phase-shifting, we developed genetic techniques that link behavior to single cell-type resolution within the Drosophila central brain. We focused on the unknown function of the 10 PDFcontaining large ventral lateral neurons (l-LNvs) of the Drosophila circadian brain network and show here that these cells function in light-dependent arousal. They also are important for phase shifting in the late-night (dawn), indicating that the circadian photoresponse is a network property and therefore non-cell-autonomous. The data further indicate that the circuits underlying light-induced arousal and circadian photoentrainment intersect at the l-LNvs and then segregate.L ight promotes arousal in diurnal species. Drosophila arousalsleep circuits remain largely uncharacterized. Exceptions are the mushroom body with a role in sleep-arousal (1, 2) as well as neurons of the pars intercerebralis (PI) and the ellipsoid body (EB) of the central complex (CC) with roles in locomotion (3, 4). Importantly, there is no indication of how the poorly understood fly sleep-movement circuits are coordinated or communicate with the well-studied brain circadian network, or whether these Ϸ150 circadian neurons impact directly on sleep or arousal.

PDF and cAMP enhance PER stability in Drosophila clock neurons

“…In addition, the l-LNvs promote light-mediated arousal, also mediated at least in part by PDF (23,29,35). Taken together with the fact that light has been shown to increase the firing rate of l-LNvs in a CRY-dependent manner (28), it is likely that lights on in the morning also potentiates the PDF-cAMP system.…”

“…Light enhances the firing rate of PDF neurons, and morning phase shifts appear to require the l-LNvs (28,29). Although TIM degradation is intimately connected with light-mediated phase shifts (24,(30)(31)(32), our recent study showed that PER degradation is also relevant (17).…”

CRYPTOCHROME-mediated phototransduction by modulation of the potassium ion channel β-subunit redox sensor

“…Subsequent work on the LNv indicates that these neurons also mediate light-driven arousal behavior (9)(10)(11). The CRY-dependent rapid electrophysiological response to blue light recorded in the LNv suggests that the loss of CRY attenuates acute behavioral arousal responses to blue light, but not to wavelengths beyond its absorbance cutoff above 530 nm (1).…”

“…CRY is expressed in a small subset of central brain circadian, arousal, and photoreceptor neurons in D. melanogaster and other insects, including the large lateral ventral neuron (LNv; l-LNv) subset (1,2,7,8). The l-LNvs are light-activated arousal neurons (1,2,(9)(10)(11), whereas the small lateral ventral neurons (s-LNvs) are critical for circadian function (5,12). Previous results suggest that light activated arousal is likely attenuated in cry-null mutants.…”

CRYPTOCHROME mediates behavioral executive choice in response to UV light

“…For insects, CRY is characterized as the primary photoreceptor for blue-light-activated circadian entrainment (15)(16)(17)(18)(19)(20)(21). CRY-expressing large LNvs (l-LNvs) also mediate acute behavioral arousal responses to blue-light-containing spectra (4)(5)(6)(7). Arousal and circadian functions are not strictly segregated between the LNv subsets because the small LNvs (s-LNvs) also contribute to arousal (5), and clock cycling is robustly altered in the l-LNv in response to light entrainment cues (22,23).…”