Use of chemogenetic approach to study cholinergic modulation of learning in a Go/NoGo visual discrimination task.

MACARENA AMIGO DURAN; NOEL FEDERMAN; SEBASTIAN A. ROMANO; ANTONIA MARIN BURGIN

Buenos AIres

Congreso; XXXVII Congress of the Argentine Society for Research in Neuroscience (SAN). Buenos Aires; 2022

SAN

Acetylcholine (ACh) has a role in hippocampal-related cognitive functions, including learning and memory. Previous work in the laboratory has shown that endogenous ACh release into the dentate gyrus of the hippocampus produces a reconfiguration of inhibitory circuits, which results in a net disinhibition of excitatory neurons, favoring plasticity of incoming inputs. Our hypothesis is that an endogenous release of acetylcholine can promote learning. For this, we developed a behavioral task to study contextual discrimination in head fix mice, using virtual reality. We used a chemogenetic approach to endogenously release ACh during learning by using Chat-HM3DQ mice injected with CNO. Water restricted animals were trained to perform a GO/NO GO visual discrimination task, in which the animal learns to drink water or not depending on the virtual visual context. We designed four increasingly difficult visual discrimination contexts to evaluate cholinergic modulation of learning. Preliminary results show that animals with increased cholinergic activity learn the task faster than control animals. In conclusion, we developed a behavioral paradigm suited to probing the neural basis of learning spatial context and its flexibility with neuromodulators.