Cholinergic modulation reorganizes dentate gyrus microcircuits

NOEL FEDERMAN; GUILLERMO M. LANUZA; MORA B. OGANDO; LUCIANO BRUM; ANTONIA MARIN BURGIN; DIEGO ARRIBAS; LUIS MORELLI

Congreso; XXXIII Sociedad Argentina de Investigación en Neurociencias (SAN); 2018

Neurogenesis in the adulthood continuously provides the dentate gyrus of the mouse hippocampus with pools of new granule cells (GC) that integrate into the network. When afferent inputs arrive to DG, immature neurons (4 weeks old-4wpiGC) respond with higher excitability, lower specificity and a different ability to decode temporal information than mature GCs (matGC). These differences in processing are due to a difference in inhibitory circuits that mostly restrict matGC. In this work we wanted to evaluate how neuromodulators, in particular acetylcholine, affects processing of inputs in both matGC and 4wpiGC.Using pharmacologic and optogenetic tools combined with electrophysiological recordings, we observed that, upon cholinergic activation, matGCs increase their responses to afferent stimuli, whereas no changes were seen for 4wpiGC. At the synaptic level, we observed a reduction in the inhibitory component of the response, which was more prominent for matGC. This produced an increase in the excitation to inhibition balance that explains the differential activity pattern. Furthermore, upon a high frequency stimulation protocol that is normally insufficient to produce potentiation, we could induce LTP if we pared it with optogenetic activation of cholinergic axons.We conclude that acetycholine can provide a temporal window of reduced inhibition, in which the information processing and plasticity rules of GCs change, possibly adapting the encoding to the behavioral demands.