Olfactory learning potentiates long-range cortical GABAergic inputs onto adult-born neurons
Abstract
Adult neurogenesis in the olfactory bulb (OB) contributes to structural and functional plasticity, influencing olfactory perception, learning, and memory. Adult-born granule cells (abGCs) exhibit unique morphological, electrophysiological, and synaptic properties compared to their neonatally born counterparts, suggesting a specialized role in olfactory processing. In the OB, such processing relies both on sensory inputs from the olfactory epithelium as well as top-down cortical feedback, which encompass both glutamatergic and GABAergic projections from the olfactory cortex back to the OB. While abGCs are known to integrate both bottom-up sensory inputs and top-down cortical projections, the specific connectivity and functional influence of cortical GABAergic inputs on abGCs remain largely unexplored. In this study, we investigated whether activity of cortical GABAergic projections is modulated by olfactory learning, how they impact olfactory behavior and whether these connections selectively influence mature abGCs. Using in vivo fiber photometry following odor-reward associative conditioning, we found odor- and reward-dependent activity of cortical GABAergic projections during learning session. Furthermore, their functional role was revealed using optogenetic activation which impaired both the acquisition and the reversal of an odor-reward association. Ex vivo patch-clamp recordings demonstrated that olfactory learning potentiates cortical GABAergic inputs specifically onto abGCs, and morphological analysis confirmed that learning increases the number of cortical GABAergic synapses. These findings highlight a novel mechanism by which top-down inhibitory control from the olfactory cortex selectively targets abGC activity during olfactory learning. Our results provide new insights into the functional specialization of abGCs and their role in adaptive olfactory behaviors.
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BibTeX
@misc{peroni2026olfactory,
title = {{Olfactory learning potentiates long-range cortical GABAergic inputs onto adult-born neurons}},
author = {Enzo Peroni and Claire-Hélène de Badts and Gabriel Lepousez and Alya Hiridjee and Justin Renvoise and Ilta Lafosse and Sébastien Wagner and Elise Jacquemet and Pierre-Marie Lledo and Mariana Alonso and Antoine Nissant},
howpublished = {HAL},
year = {2026},
month = may,
doi = {10.64898/2026.05.29.728424},
url = {https://hal.science/hal-05862123v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Olfactory learning potentiates long-range cortical GABAergic inputs onto adult-born neurons
AU - Enzo Peroni
AU - Claire-Hélène de Badts
AU - Gabriel Lepousez
AU - Alya Hiridjee
AU - Justin Renvoise
AU - Ilta Lafosse
AU - Sébastien Wagner
AU - Elise Jacquemet
AU - Pierre-Marie Lledo
AU - Mariana Alonso
AU - Antoine Nissant
PY - 2026
DA - 2026/05/31
PB - HAL
DO - 10.64898/2026.05.29.728424
UR - https://hal.science/hal-05862123v1
AB - Adult neurogenesis in the olfactory bulb (OB) contributes to structural and functional plasticity, influencing olfactory perception, learning, and memory. Adult-born granule cells (abGCs) exhibit unique morphological, electrophysiological, and synaptic properties compared to their neonatally born counterparts, suggesting a specialized role in olfactory processing. In the OB, such processing relies both on sensory inputs from the olfactory epithelium as well as top-down cortical feedback, which encompass both glutamatergic and GABAergic projections from the olfactory cortex back to the OB. While abGCs are known to integrate both bottom-up sensory inputs and top-down cortical projections, the specific connectivity and functional influence of cortical GABAergic inputs on abGCs remain largely unexplored. In this study, we investigated whether activity of cortical GABAergic projections is modulated by olfactory learning, how they impact olfactory behavior and whether these connections selectively influence mature abGCs. Using in vivo fiber photometry following odor-reward associative conditioning, we found odor- and reward-dependent activity of cortical GABAergic projections during learning session. Furthermore, their functional role was revealed using optogenetic activation which impaired both the acquisition and the reversal of an odor-reward association. Ex vivo patch-clamp recordings demonstrated that olfactory learning potentiates cortical GABAergic inputs specifically onto abGCs, and morphological analysis confirmed that learning increases the number of cortical GABAergic synapses. These findings highlight a novel mechanism by which top-down inhibitory control from the olfactory cortex selectively targets abGC activity during olfactory learning. Our results provide new insights into the functional specialization of abGCs and their role in adaptive olfactory behaviors.
ER -