| Title: |
ASSESSING THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN EXECUTIVE FUNCTION USING TOUCHSCREEN TECHNOLOGY IN RAT MODELS |
| Authors: |
de Medeiros, Gabriela; Azizi, Pegah; Langa, Francina; 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); Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); 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: |
E-Book of Abstractsfens.org/2022 ; FENS FORUM 2022 ; https://pasteur.hal.science/pasteur-05511186 ; FENS FORUM 2022, Federation of European Neuroscience Societies, Jul 2022, Paris, France. pp.BOARD NUMBER: S05-069/ POSTER SESSION 05 - SECTION: TEMPORAL COGNITION, RHYTHMS & ATTENTION ; https://forum2022.fensforum.org/ |
| Publisher Information: |
CCSD |
| Publication Year: |
2022 |
| Subject Terms: |
[SDV]Life Sciences [q-bio]; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
| Subject Geographic: |
Paris; France |
| Description: |
International audience ; Dysfunctional α7 nicotinic acetylcholine receptors (α7*nAChRs) and their genetic regulation have been associated with several neuropsychiatric diseases including schizophrenia (SCZ) and Alzheimer’s disease. Preclinical studies revealed that α7*nAChR ligands can improve executive function, commonly impaired across many neuropsychiatric disorders. Yet, a translational gap prevents these findings from resulting into clinically effective treatments. Our goal was to refine our understanding of the role of α7*nAChRs in executive function.We generated transgenic rats knockout for the α7 nicotinic subunit gene (α7KO) using the zinc finger nuclease technology. We submitted α7KO and their controls to two tests assessing executive function: the continuous performance task (CPT), a task of sustained attention which involves selection, vigilance and control; and the visual discrimination (VD) task, measuring associative learning and perceptive ability. These tasks were adapted from clinical research in a highly translational manner, thanks to the use of a touchscreen-based experimental setting. Strikingly, α7KO rats showed a response bias towards a global over-responding in the CPT, a strategy that was detrimental to task performance as reflected in a lower discrimination sensitivity - a deficit commonly reported in SCZ patients, and a higher persistence in error making. α7KO and control rats performed equally well and adopted identical strategies in the VD task. As in the CPT, α7KO rats also displayed a global over-responding to the screen in the VD task. Our results suggest that α7nAChRs are crucial to executive functioning for regulating behavioral inhibition, thereby facilitating the performance in tasks demanding high attentional load. |
| Document Type: |
conference object |
| Language: |
English |
| Availability: |
https://pasteur.hal.science/pasteur-05511186 |
| Accession Number: |
edsbas.5888386C |
| Database: |
BASE |