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Guided by gut sensory cues, humans and animals prefer nutritive sugars over non-caloric sweeteners, but how the gut steers such preferences remains unknown. In the intestine, neuropod cells synapse with vagal neurons to convey sugar stimuli to the brain within seconds. Here, we found that cholecystokinin (CCK)-labeled duodenal neuropod cells differentiate and transduce luminal stimuli from sweeteners and sugars to the vagus nerve using sweet taste receptors and sodium glucose transporters. The two stimulus types elicited distinct neural pathways: while sweetener stimulated purinergic neurotransmission, sugar stimulated glutamatergic neurotransmission. To probe the contribution of these cells to behavior, we developed optogenetics for the gut lumen by engineering a flexible fiberoptic. We showed that preference for sugar over sweetener in mice depends on neuropod cell glutamatergic signaling. By swiftly discerning the precise identity of nutrient stimuli, gut neuropod cells serve as the entry point to guide nutritive choices.

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Animals innately prefer caloric sugars over non-caloric sweeteners. Such preference depends on the sugar entering the intestine. [1][2][3][4] Although the brain is aware of the stimulus within seconds, [5][6][7][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 animal's internal preference toward the caloric sugar. Main TextThe cephalic senses guide our decision to eat. But what happens next, inside the gut, is essential for our eating preferences.As early as 1952, it was known that animals prefer the side of a T-maze if rewarded by nutrients delivered directly into the stomach. 1 Although the responses depend on the nutrient's caloric value, 7,8,11 how this value is signaled by the gut epithelium to drive preference is unknown. Of all macronutrients, sugars and available analogs have the most defined sensory properties. For instance, sucrose -a compound sugar made of D-glucose and fructose-contains both taste and calorie, whereas non-caloric sweeteners, like sucralose, carry only taste. Animals have an innate preference for sucrose over non-caloric sweeteners, even in the absence of taste. 3,12-14 Such preference depends on the sugar entering the intestine. 2,3,15,16 But slow acting intestinal hormones cannot account for the effect, 17 because the brain perceives stimuli from nutrients entering the small intestine within seconds. 6,8,10 Thus, a fast intestinal sensor must exist to steer the animal towards the caloric sugar.A gut sense for sweets. Intestinal signals arising from the lumen are relayed to the brain via the vagus nerve. 6,10,11 The vagus responds within seconds to an intraluminal stimulus of sucrose, 6,10,18 but the response to other sugars, including non-caloric sweeteners, is unclear. We therefore tested vagal firing responses to a panel of sugars: sucrose, D-glucose, fructose, galactose, maltodextrin, alpha-methylglucopyranoside (α-mgp), saccharin, acesulfame-K, and sucralose. All stimuli were perfused at physiological concentrati...

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We explore in detail the nontrivial and chaotic behavior of the traffic model proposed by Toledo et al. [Phys. Rev. E 70, 016107 (2004)] due to the richness of behavior present in the model, in spite of the fact that it is a minimalistic representation of basic city traffic dynamics. The chaotic behavior, previously shown for a given lower bound in acceleration/brake ratio, is examined more carefully and the region in parameter space for which we observe this nontrivial behavior is found. This parameter region may be related to the high sensitivity of traffic flow that eventually leads to traffic jams. Approximate scaling laws are proposed.

In the hope of making passenger travel times shorter and more reliable, many cities are introducing dedicated bus lanes (e.g., Bogota, London, Miami). Here we show that chaotic travel times are actually a natural consequence of individual bus function, and hence of public transport systems more generally, i.e., chaotic dynamics emerge even when the route is empty and straight, stops and lights are equidistant and regular, and loading times are negligible. More generally, our findings provide a novel example of chaotic dynamics emerging from a single object following Newton's laws of motion in a regularized one-dimensional system.