Liu, W. W. | bioRxiv Science

bioRxiv2026

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.

neuroscience↗

bioRxiv2020

A gut sensor for sugar preference

Summary Paragraph/AbstractAnimals innately prefer caloric sugars over non-caloric sweeteners. Such preference depends on the sugar entering the intestine.1-4 Although the brain is aware of the stimulus within seconds,5-8 how the gut discerns the caloric sugar to guide choice is unknown. Recently, we discovered an intestinal transducer, known as the neuropod cell.9,10 This cell synapses with the vagus to inform the brain about glucose in the gut in milliseconds.10 Here, we demonstrate that neuropod cells distinguish a caloric sugar from a non-caloric sweetener using the electrogenic sodium glucose co-transporter 1 (SGLT1) or sweet taste receptors. Activation of neuropod cells by non-caloric sucralose leads to ATP release, whereas the entry of caloric sucrose via SGLT1 stimulates glutamate release. To interrogate the contribution of the neuropod cell to sugar preference, we developed a method to record animal preferences in real time while using optogenetics to silence or excite neuropod cells. We discovered that silencing these cells, or blocking their glutamatergic signaling, renders the animals unable to recognize the caloric sugar. And, exciting neuropod cells leads the animal to consume the non-caloric sweetener as if it were caloric. By transducing the precise identity of the stimuli entering the gut, neuropod cells guide an animals internal preference toward the caloric sugar.

neuroscience↗