Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information

Animals must balance the urgent need to find food during starvation with the critical necessity to avoid toxic substances to ensure their survival. In Drosophila, specialized Gustatory Receptors (GRs) expressed in Gustatory Receptor Neurons (GRNs) are critical for distinguishing between nutritious a...

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Main Authors: Rubén Mollá-Albaladejo, Manuel Jiménez-Caballero, Juan Antonio Sanchez-Alcaniz
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-07-01
Series:eLife
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Online Access:https://elifesciences.org/articles/100947
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author Rubén Mollá-Albaladejo
Manuel Jiménez-Caballero
Juan Antonio Sanchez-Alcaniz
author_facet Rubén Mollá-Albaladejo
Manuel Jiménez-Caballero
Juan Antonio Sanchez-Alcaniz
author_sort Rubén Mollá-Albaladejo
collection DOAJ
description Animals must balance the urgent need to find food during starvation with the critical necessity to avoid toxic substances to ensure their survival. In Drosophila, specialized Gustatory Receptors (GRs) expressed in Gustatory Receptor Neurons (GRNs) are critical for distinguishing between nutritious and potentially toxic food. GRNs project their axons from taste organs to the Subesophageal Zone (SEZ) in the Central Brain (CB) of Drosophila, where gustatory information is processed. Although the roles of GRs and GRNs are well-documented, the processing of gustatory information in the SEZ remains unclear. To better understand gustatory sensory processing and feeding decision-making, we molecularly characterized the first layer of gustatory interneurons, referred to as Gustatory Second-Order Neurons (G2Ns), which receive direct input from GRNs. Using trans-synaptic tracing with trans-Tango, cell sorting, and bulk RNAseq under fed and starved conditions, we discovered that G2Ns vary based on gustatory input and that their molecular profile changes with the fly’s metabolic state. Further data analysis has revealed that a pair of neurons in the SEZ, expressing the neuropeptide Leucokinin (SELK neurons), receive simultaneous input from GRNs sensing bitter (potentially toxic) and sweet (nutritious) information. Additionally, these neurons also receive inputs regarding the starvation levels of the fly. These results highlight a novel mechanism of feeding regulation and metabolic integration.
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spelling doaj-art-3b68bcb849c3489a8dbac81ececf25f92025-08-20T03:28:43ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011310.7554/eLife.100947Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic informationRubén Mollá-Albaladejo0https://orcid.org/0000-0001-9897-9525Manuel Jiménez-Caballero1Juan Antonio Sanchez-Alcaniz2https://orcid.org/0000-0002-4900-5086Instituto de Neurociencias, CSIC-UMH, San Juan de Alicante, SpainInstituto de Neurociencias, CSIC-UMH, San Juan de Alicante, SpainInstituto de Neurociencias, CSIC-UMH, San Juan de Alicante, SpainAnimals must balance the urgent need to find food during starvation with the critical necessity to avoid toxic substances to ensure their survival. In Drosophila, specialized Gustatory Receptors (GRs) expressed in Gustatory Receptor Neurons (GRNs) are critical for distinguishing between nutritious and potentially toxic food. GRNs project their axons from taste organs to the Subesophageal Zone (SEZ) in the Central Brain (CB) of Drosophila, where gustatory information is processed. Although the roles of GRs and GRNs are well-documented, the processing of gustatory information in the SEZ remains unclear. To better understand gustatory sensory processing and feeding decision-making, we molecularly characterized the first layer of gustatory interneurons, referred to as Gustatory Second-Order Neurons (G2Ns), which receive direct input from GRNs. Using trans-synaptic tracing with trans-Tango, cell sorting, and bulk RNAseq under fed and starved conditions, we discovered that G2Ns vary based on gustatory input and that their molecular profile changes with the fly’s metabolic state. Further data analysis has revealed that a pair of neurons in the SEZ, expressing the neuropeptide Leucokinin (SELK neurons), receive simultaneous input from GRNs sensing bitter (potentially toxic) and sweet (nutritious) information. Additionally, these neurons also receive inputs regarding the starvation levels of the fly. These results highlight a novel mechanism of feeding regulation and metabolic integration.https://elifesciences.org/articles/100947feedingbehaviorneural circuitsgenetics
spellingShingle Rubén Mollá-Albaladejo
Manuel Jiménez-Caballero
Juan Antonio Sanchez-Alcaniz
Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
eLife
feeding
behavior
neural circuits
genetics
title Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
title_full Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
title_fullStr Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
title_full_unstemmed Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
title_short Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information
title_sort molecular characterization of gustatory second order neurons reveals integrative mechanisms of gustatory and metabolic information
topic feeding
behavior
neural circuits
genetics
url https://elifesciences.org/articles/100947
work_keys_str_mv AT rubenmollaalbaladejo molecularcharacterizationofgustatorysecondorderneuronsrevealsintegrativemechanismsofgustatoryandmetabolicinformation
AT manueljimenezcaballero molecularcharacterizationofgustatorysecondorderneuronsrevealsintegrativemechanismsofgustatoryandmetabolicinformation
AT juanantoniosanchezalcaniz molecularcharacterizationofgustatorysecondorderneuronsrevealsintegrativemechanismsofgustatoryandmetabolicinformation