ipRGCs utilize non-overlapping circuits to drive phase shifts, masking and circadian photoentrainment

Abstract

Purpose : Intrinsically photosensitive retinal ganglion cells (ipRGCs) are essential for many light-mediated behaviors such as circadian photoentrainment, pupillary light reflex and acute regulation of activity (masking) and sleep. The specific circuits mediating these behaviors, however, are not completely understood. In addition, most studies use wheel running as a measure of locomotor responses to light, a behavior that might be regulated by light differently than general activity or core body temperature. Here to we sought to determine whether ipRGC circuits relaying light information for circadian photoentrainment are similar to those driving phase shifting and the acute regulation of general activity and body temperature.

Methods : To investigate the ipRGC circuits that drive distinct light-mediated behaviors, we used mice that lack most ipRGC subtypes (Opn4^DTA/+), but are still able to photoentrain to a light/dark (LD) cycle. Opn4^DTA/+ and control mice were implanted with telemetry devices to measure core body temperature and general activity in response to 3-h light pulses across a range of light intensities (0.1, 1, 10, 100 and 500 lux) during the dark period of a 12:12 LD cycle. Masking responses and phase shifts to these 3-h light pulses were calculated and compared between the different genotypes. In addition, we examined photoentrainment to a skeleton photoperiod, where animals are exposed to two 1-hour pulses of light corresponding to dawn and dusk.

Results : As expected, both wild-type and Opn4^DTA/+ mice photoentrained to a 12:12 LD cycle, however, Opn4^DTA/+ mice exhibited deficits in masking to 3-h pulses of light across all light intensities. Wild-type mice displayed a shift in the onset of general activity and core body temperature in response to the 3-h light pulses at all light intensities (surprisingly, even as low as 0.1 lux), whereas Opn4^DTA/+ mice displayed a similar shift only at high light intensities (500 lux). Despite the lack of phase shifts in Opn4^DTA/+ mice in the onset of their general activity/core body temperature to a 3-h light pulse at 0.1 lux, remarkably, these animals were still capable of photoentrainment to a skeleton photoperiod at this light intensity.

Conclusions : These results suggest that the circuits required for masking and phase shifting to light may be distinct from those regulating circadian photoentrainment.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.