4.8 Article

Distinct contribution of cone photoreceptor subtypes to the mammalian biological clock

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2024500118

Keywords

suprachiasmatic nucleus; cones; photoentrainment; circadian; in vivo electrophysiology

Funding

  1. European Research Council (ERC) [834513]
  2. Velux Stiftung (Zurich, Switzerland) [1131]
  3. European Research Council (ERC) [834513] Funding Source: European Research Council (ERC)

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The study reveals the significant role of cone photoreceptors in regulating circadian rhythms, transmitting light information to the suprachiasmatic nuclei, and affecting their electrical activity levels.
Ambient light detection is important for the synchronization of the circadian clock to the external solar cycle. Light signals are sent to the suprachiasmatic nuclei (SCN), the site of the major circadian pacemaker. It has been assumed that cone photoreceptors con-tribute minimally to synchronization. Here, however, we find that cone photoreceptors are sufficient for mediating entrainment and transmitting photic information to the SCN, as evaluated in mice that have only cones as functional photoreceptors. Using in vivo electrophysiological recordings in the SCN of freely moving cone-only mice, we observed light responses in SCN neuronal activity in response to 60-s pulses of both ultraviolet (UV) (lambda(max) 365 nm) and green (lambda(max) 505 nm) light. Higher irradiances of UV light led to irradiance-dependent enhancements in SCN neuronal activity, whereas higher irradiances of green light led to a reduction in the sustained response with only the transient response remain-ing. Responses in SCN neuronal activity decayed with a half-max time of similar to 9 min for UV light and less than a minute for green light, indicating differential input between short-wavelength-sensitive and mid-wavelength-sensitive cones for the SCN responsiveness. Furthermore, we show that UV light is more effective for photo-entrainment than green light. Based on the lack of a full sustained response in cone-only mice, we confirmed that rapidly alternating light levels, rather than slowly alternating light, caused substantial phase shifts. Together, our data provide strong evidence that cone types contribute to photoentrainment and differentially affect the electrical activity levels of the SCN.

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