| Title: |
UNRAVELLING THE ROLE OF PREFRONTAL ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INHIBITORY CONTROL IN PHYSIOLOGICAL AND PATHOLOGICAL CONTEXTS: A BEHAVIORAL INVESTIGATION USING TOUCHSCREEN TECHNOLOGY |
| Authors: |
de Medeiros, Gabriela; Bouarab, Chloé; Azizi, Pegah; Pons, Stéphanie; 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); Federation of European Neuroscience Societies; 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: |
FENS FORUM 2024 ; https://pasteur.hal.science/pasteur-05511192 ; FENS FORUM 2024, Federation of European Neuroscience Societies, Jun 2024, Vienna, Austria ; https://forum2024.fensforum.org/welcome-to-the-fens-forum-2024/ |
| Publisher Information: |
CCSD |
| Publication Year: |
2024 |
| Subject Terms: |
[SDV]Life Sciences [q-bio]; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
| Subject Geographic: |
Vienna; Austria |
| 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 transgenic rats, viral vector-mediated local gene expression, touchscreen-based behavioral assays and pharmacological manipulations, with the objective to unravel the role of these receptors with region-specific resolution. Our findings show that knockout rats 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, and unlikely to be due to compensatory alterations in non-⍺7 nAChR subunits’ expression. We further aim at unravelling the importance of α7*nAChRs expressed in the infralimbic cortex and in the anterior cingulate cortex (ACC) in the modulation of cognition by re-expressing these receptors specifically in these regions in α7KO rats. Finally, we aim at identifying the contribution of α7*nAChRs to the development of cognitive deficits in the context of neuropsychiatric disorders, and, in particular, the putative interaction between these receptors and the amyloid beta peptide in a rat model of AD. 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-05511192 |
| Accession Number: |
edsbas.E73DF7D5 |
| Database: |
BASE |