| Title: |
Unravelling the role of alpha7 nicotinic acetylcholine receptors in inhibitory control in physiological and pathological contexts, using transgenic rats and touchscreen technology |
| Authors: |
Bouarab, Chloé; Ferreira de Medeiros, Gabriela; Azizi, Pegah; Pons, Stéphanie; Maskos, Uwe; Besson, Morgane |
| Contributors: |
Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC); Institut Pasteur Paris (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut Pasteur Paris (IP); European Brain and Behaviour Society; ANR-21-CE37-0026,NICOPTOTOUCH,Nouvelles approches comportementales et (opto)pharmacologiques chez le rat pour l'étude des récepteurs nicotiniques alpha7 de l'acétylcholine en lien avec des endophénotypes neuropsychiatriques(2021) |
| Source: |
Meeting of the European Brain and Behaviour Society (EBBS) 2025 ; https://pasteur.hal.science/pasteur-05511200 ; Meeting of the European Brain and Behaviour Society (EBBS) 2025, European Brain and Behaviour Society, Jun 2025, Bordeaux, France ; https://ebbs2025.azuleon.org/programme |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Subject Terms: |
[SDV]Life Sciences [q-bio]; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
| Subject Geographic: |
Bordeaux; France |
| Description: |
International audience ; Dysfunctional α7 nicotinic acetylcholine receptors (α7*nAChRs) and their genetic regulation have been associated with several neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease (AD). Preclinical studies revealed that α7*nAChR ligands can improve executive function, commonly impaired across neuropsychiatric disorders. Yet, a translational gap prevents these findings from resulting into clinically effective treatments. To tackle this translational gap, we combine approaches such as pharmacological modulation, transgenic rats and touchscreen-based behavioral assays to investigate the role of these receptors notably with region-specific resolution. Our findings show that rats knockout for the α7 subunit gene (α7KO) present a general deficit in inhibitory control as observed in the continuous performance task and the differential reinforcement of low-rates of responding task, which seems unrelated to deficits in attention, learning or motivation. In a second set of experiments, we aim at identifying the contribution of α7*nAChRs to the development of cognitive deficits in the context of amyloid beta-mediated diseases, and the putative interaction between these receptors and the amyloid beta peptide in a rat model. Indeed, a particular role of α7*nAChRs has been suggested in Alzeihmer’s disease with fewer of these receptors observed in patients and their putative blockade by amyloid beta. To untangle this relationship, we use a viral vector-mediated local gene expression to express a mutated form of the human APP leading to an over production of amyloid beta. So far, our approach has revealed a crucial role of α7*nAChRs in response inhibition and represents a promising tool to screen new α7*nAChR ligands for therapeutical purposes. |
| Document Type: |
conference object |
| Language: |
English |
| Availability: |
https://pasteur.hal.science/pasteur-05511200 |
| Accession Number: |
edsbas.DE1116E1 |
| Database: |
BASE |