Melatonin modulates habituation learning via the convergent action of two MT1-type receptors.
- 1Laboratoire MeLiS, Universite Claude Bernard Lyon 1 - CNRS UMR5284 - Inserm U1314, Faculte de Medecine et de Pharmacie, 8 avenue Rockefeller, 69008 Lyon, France
Abstract
Melatonin is a hormone produced by the pineal gland and retina, with roles in sleep and circadian rhythms as well as other neuronal processes, including the regulation of learning and memory. Using larval zebrafish, we previously identified Melatonin as a potent modulator of habituation learning: the progressive suppression of responses to a repeated stimulus. Here we have extended these analyses and have found that Melatonin has strong effects on separate aspects of habituation learning: it potentiates habituation of response probability and latency, while simultaneously inhibiting habituation of movement amplitude and duration. We performed a systematic CRISPR mutagenesis of all six zebrafish Melatonin receptors, and found that only two MT1-type receptors (Mtnr1aa and Mtnr1al) are required for Melatonin's effects on habituation. These receptors showed a cooperative interaction, with each individual mutant showing reduced sensitivity to Melatonin, and mtnr1aa;mtnr1al double mutants showing complete insensitivity. To map where these receptors act, we used whole-brain activity mapping. Despite distinct footprints, both perturbed a shared set of brain areas, including the torus longitudinalis, cerebellum, and preoptic area, with the double mutant producing the most extensive phenotype by combining and expanding the effects seen in each single mutant. Thus, we propose that two MT1-type receptors act at overlapping circuit nodes to reinforce Melatonin's bidirectional control of learning.
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BibTeX
@misc{baas2026melatonin,
title = {{Melatonin modulates habituation learning via the convergent action of two MT1-type receptors.}},
author = {D. Baas and I. Darvaux-Hubert and R. Dorado-Doncel and A. Hsiao and L. Broisin and A. R. El Hassan and J. Perrichet and O. Randlett},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.749335},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.749335v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Melatonin modulates habituation learning via the convergent action of two MT1-type receptors.
AU - D. Baas
AU - I. Darvaux-Hubert
AU - R. Dorado-Doncel
AU - A. Hsiao
AU - L. Broisin
AU - A. R. El Hassan
AU - J. Perrichet
AU - O. Randlett
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.749335
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.749335v1
AB - Melatonin is a hormone produced by the pineal gland and retina, with roles in sleep and circadian rhythms as well as other neuronal processes, including the regulation of learning and memory. Using larval zebrafish, we previously identified Melatonin as a potent modulator of habituation learning: the progressive suppression of responses to a repeated stimulus. Here we have extended these analyses and have found that Melatonin has strong effects on separate aspects of habituation learning: it potentiates habituation of response probability and latency, while simultaneously inhibiting habituation of movement amplitude and duration. We performed a systematic CRISPR mutagenesis of all six zebrafish Melatonin receptors, and found that only two MT1-type receptors (Mtnr1aa and Mtnr1al) are required for Melatonin's effects on habituation. These receptors showed a cooperative interaction, with each individual mutant showing reduced sensitivity to Melatonin, and mtnr1aa;mtnr1al double mutants showing complete insensitivity. To map where these receptors act, we used whole-brain activity mapping. Despite distinct footprints, both perturbed a shared set of brain areas, including the torus longitudinalis, cerebellum, and preoptic area, with the double mutant producing the most extensive phenotype by combining and expanding the effects seen in each single mutant. Thus, we propose that two MT1-type receptors act at overlapping circuit nodes to reinforce Melatonin's bidirectional control of learning.
ER -