Biology subjects

Lopez-Cruz, A.

Publications and source records attributed to Lopez-Cruz, A..

3 recordsLinked to original sources

bioRxiv2026

Opposing GIPR brainstem circuits differentially control feeding behaviour

Central glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling is required for the efficacy of GIP-based obesity therapeutics, yet how distinct subpopulations of GIPR neurons shape appetite remains undefined. Here we show that GIPR neurons in adjacent brainstem nuclei, the area postrema (AP) and nucleus tractus solitarius (NTS), exert opposing control over ingestion. We find GIPRAP neurons dampen post-ingestive satiation, permitting hyperphagia, whereas GIPRNTS neurons are anorectic. In line with this model, we show Gipr expression in AP, but not NTS, neurons is necessary for appetite suppression following GIPR antagonism. Additionally, we reveal that GIPR neurons in the AP and NTS occupy distinct gut-brain circuits, and are differentially sensitive to obesity-driven circuit remodelling. These data offer a framework for understanding how current GIPR agonist and antagonist strategies elicit weight loss.

neuroscience↗

bioRxiv2026

Functional segregation of body-brain signals in the area postrema

Nausea arises from activation of specialized neurons in the area postrema (AP)1-8. The AP also mediates much of the satiety produced by GLP1R agonists9-12, suggesting a broader role in non-aversive physiology, yet the functions of AP cell types are not well understood. Here, we have used optical recordings in behaving mice to systematically define the natural regulation of an array of AP neurons, including the cell types that are principal targets of widely-used weight loss drugs. We discover that neurons expressing GFRAL, the receptor for the sickness-related hormone GDF15, are unexpectedly activated when mice consume food rich in fat. This fat-specific GFRAL neuron activation is required for fat satiation but does not involve GDF15 or canonical gut-brain pathways. Instead, "anti-nausea" neurons expressing GIPR, which directly inhibit GFRAL neurons, are selectively activated by sugar, enabling macronutrient-specific gating of GFRAL responses. In addition, we show that CALCR neurons link intestinal hyperosmolality to the suppression of feeding, whereas PRLHR neurons respond to changes in blood volume and pressure. These findings reveal a broad role for AP cell types in sensing and responding to physiologic signals unrelated to nausea. They also reveal that GFRAL and GIPR neurons, which are key targets of the weight-loss drug tirzepatide, have a natural function in sensing ingestion of fat and sugar, respectively.

neuroscience↗

bioRxiv2018

Parallel multimodal circuits control an innate foraging behavior

Foraging strategies that enable animals to locate food efficiently are composed of highly conserved behavioral states with characteristic features. Here, we identify parallel multimodal circuit modules that control an innate foraging state -- local search behavior -- after food removal in the nematode Caenorhabditis elegans. Two parallel groups of chemosensory and mechanosensory glutamatergic neurons that detect food-related cues trigger local search by inhibiting separate integrating neurons through a metabotropic glutamate receptor, MGL-1. The chemosensory and mechanosensory modules are separate and redundant, as glutamate release from either can drive the full behavior. Spontaneous activity in the chemosensory module encodes information about the time since the last food encounter and correlates with the foraging behavior. In addition, the ability of the sensory modules to control local search is gated by the internal nutritional state of the animal. This multimodal circuit configuration provides robust control of an innate adaptive behavior.

neuroscience↗