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Jarvie, B. C.

Publications and source records attributed to Jarvie, B. C..

4 recordsLinked to original sources

Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem

Digestion requires precisely timed transit of food through the gastrointestinal tract. Here we show that emptying of food from the stomach occurs in discrete pulses, separated by pauses that allow the proximal duodenum to clear before the next bolus arrives. By combining X-ray fluoroscopy of the gut with calcium imaging of the brainstem, we identify a population of neurons defined by expression of neuropeptide FF (NPFF) that tracks these duodenal dynamics. Stimulation of NPFF neurons induces a coordinated response that inhibits gastric emptying and accelerates intestinal transit, thereby clearing the proximal intestine for the next bolus of food. These neurons also bidirectionally control food intake through cholinergic signaling in the gut. These findings reveal a mechanism by which brainstem transforms the sensory detection of nutrients in the duodenum into the opposing control of the stomach and intestine. They also establish an experimental approach for dissecting gut-brain signaling in behaving animals.

neuroscience↗

An orthogonal TRAP enables intersectional genetic access to activated neurons in the mouse brain

The study of neural circuits has been greatly enabled by methods for obtaining genetic access to activated neurons. However, these approaches typically tag neurons based on their response to only a single stimulus, which limits the ability to define precise subpopulations of cells. Here we describe an approach (X-TRAP) in which the activity-dependent expression of Flp recombinase is gated by branaplam, a small molecule that triggers splicing of the X-ON switch. We show that X-TRAP knock-in mice exhibit undetectable Flp recombination in the absence of drug and that branaplam treatment results in robust induction of recombination selectively in neurons that express FOS. Moreover, we show that X-TRAP is orthogonal to the widely-used TRAP system, such that these two approaches can be used in the same animal to label cells with Cre and Flp recombination in response to two different stimuli. We apply this strategy to map neural circuits that control food intake. This approach for intersectional, activity-dependent genetic labeling should enhance our ability to identify the neural correlates of behavior.

neuroscience↗

Ingestion-activated CGRP neurons control learning but not satiety

Calcitonin Gene-Related Peptide (CGRP) neurons in the parabrachial nucleus are critical for sickness and malaise but have also been proposed to control non-aversive (rewarding) satiation. How one cell type can coordinate these opposing processes has not been explained. Here we reinvestigate the function of these cells using single-cell imaging as well as optical and chemogenetic manipulations. Contrary to current models, we show that CGRP neurons do not track cumulative food consumption, and their activity is not necessary for meal termination. Instead, we identify two distinct populations of CGRP cells, one of which responds rapidly to appetitive signals during ingestion and the other of which responds slowly to aversive visceral cues. Surprisingly, the ingestion-activated CGRP neurons are important for learning about post-ingestive effects but have little effect on food consumption. This reveals two populations of CGRP neurons that are sequentially engaged during, and responsible for, the distinct stages of post-ingestive learning.

neuroscience↗

Enteroendocrine cell types that drive food reward and aversion

Animals must learn through experience which foods are nutritious and should be consumed, and which are toxic and should be avoided. Enteroendocrine cells (EECs) are the principal chemosensors in the GI tract, but investigation of their role in behavior has been limited by the difficulty of selectively targeting these cells in vivo. Here we describe an intersectional genetic approach for manipulating EEC subtypes in behaving mice. We show that multiple EEC subtypes inhibit food intake but have different effects on learning. Conditioned flavor preference is driven by release of cholecystokinin whereas conditioned taste aversion is mediated by serotonin and substance P. These positive and negative valence signals are transmitted by vagal and spinal afferents, respectively. These findings establish a cellular basis for how chemosensing in the gut drives learning about food.

physiology↗