Neural Circuits and Systems Neuroscience
Author: Macarena Amigo Duran | Email: macky.amigo@gmail.com
Macarena Amigo-Duran1°, Julieta Campi1°, Antonia Marin-Burgin1°
1° IBioBA – MPSP – CONICET
The hippocampus is crucial for learning and memory, with the dentate gyrus (DG) playing a key role in processing incoming information and forming distinct memory representations. Our lab has shown that acetylcholine (ACh) release in the DG reconfigures inhibitory circuits, leading to excitatory neuron disinhibition and enhanced synaptic plasticity. Building on these findings, we hypothesized that ACh release boosts learning and memory. Using a head-fixed virtual reality Go/No-Go task, we assessed contextual discrimination in mice, and employed chemogenetics (Chat-hM3DQ) to increase endogenous ACh release. Our results indicate a trend towards faster task learning in animals with enhanced cholinergic activity compared to controls, and higher memory of the task tested 7 days after. We also explored how ACh modulates synaptic plasticity in the DG by studying spike timing-dependent plasticity and associative long-term potentiation (LTP) in hippocampal slices. As lateral and medial entorhinal cortex inputs are anatomically and functionally distinct, processing content-specific and contextual information, respectively, we examined their convergence in the DG and found that ACh modulates responses from both pathways and gate associative LTP induction by weakening inhibitory inputs. This mechanism could potentially enhance learning, as we observed in vivo. The results contribute to understanding how ACh-mediated neuromodulation supports cognitive flexibility and memory formation.