071 | Cholinergic Facilitation of Contextual Discrimination Learning in Mice

Cognition, Behavior, and Memory

Author: Macarena Amigo Durán | Email: macky.amigo@gmail.com

Macarena Amigo-Duran , Julieta Campi , Antonia Marin-Burgin

1° Biomedicine Research Institute of Buenos Aires – MPSP – CONICET

Acetylcholine (ACh) functions as a neuromodulator, playing a crucial role in hippocampal-associated cognitive processes such as 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. As a next step we decided to test the hypothesis that an endogenous release of acetylcholine can promote learning. For this we: 1) developed a behavioral task to study contextual discrimination in a head fix mice using virtual reality.; 2) study how increasing endogenous ACh release affects learning the task. 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.