Retinal Origins of Circadian Photoregulation's Specialized Dynamic Range and Temporal Integration

视网膜起源:昼夜节律光调节的特殊动态范围和时间整合

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Abstract

The circadian clock allows organisms to anticipate environmental changes that are driven by the earth's rotation, and synchronizes with this cycle using light(1). The clock extracts relevant parameters of illumination, responding selectively to intensities at twilight and above, and to the number of photons counted over an extended time window(2-8). These hallmark properties are thought to manifest in the brain(9). Here, we report that they emerge within specific neurons of the eye. These M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) detect light directly, using a receptor called melanopsin, and indirectly, through circuits driven by rod and cone photoreceptors(10). We find that the balance of intrinsic and extrinsic drives varies widely across M1s, and the population accounts for the dynamic range of circadian photoregulation. Both singly and collectively, M1s approach the level of temporal integration observed behaviorally. The cellular and behavioral levels match when the pupillary light reflex-another M1-driven function-shapes the light that M1s receive. This work reveals how the first steps of sensory processing are precisely formatted for specific tasks. It also introduces bioluminescence-based methods for identifying photosensitive neurons without desensitization, allowing their mechanistic study under physiological conditions.

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