Divergence of Melanopsin’s Intrinsic Properties and Downstream Actions

Opsins are light-activated receptors. A basic question is how the molecular properties of an opsin shape its effects on the organism. In mammals, melanopsin regulates perception, cognition, physiology, and mood. Because these actions are vital, an international standard has been formulated to express light in terms of melanopsin stimulation. Short wavelengths are absorbed best by melanopsin and should drive its effects most strongly. We report that melanopsin’s cellular and behavioral effects show little or even opposite wavelength sensitivity in some regimes. This divergence stems from melanopsin’s persistent activity, which generates adaptation. Wavelengths absorbed strongly by melanopsin produce high persistent activity and adaptation, giving net desensitization, whereas wavelengths absorbed weakly can produce sensitization instead. We provide a quantitative model that captures these transformations. This work indicates how the downstream actions of a molecule may diverge starkly from its intrinsic properties.