Cholinergic modulation reorganizes dentate gyrus microcircuits

MORA B. OGANDO; DIEGO ARRIBAS; LUIS MORELLI; ANTONIA MARIN BURGIN

Congreso; Meeting of the Society for Neuroscience; 2018

Neurogenesis in the adulthood continuously provides the dentate gyrus (DG) of the mouse hippocampus with pools of granule cells (GC) that integrate into the preexisting network.We have previously showed that immature GC have lower thresholds of activation than the rest of the mature GC, are less selective in their responses to afferent inputs and respond to a wider range of frequencies of afferent activity. The differences in the activation profile of immature and mature neurons are dictated by the inhibitory circuits. These results suggest that mature and immature granule cells could then represent two different codes coexisting in the same structure: A sparse-code of mature neurons with low firing rates and high selectivity, and a dense-code of immature neurons in which most neurons are active at any moment and information is encoded by variations in firing rate. In this work we wanted to evaluate how neuromodulators, in particular acetylcholine, affects processing of inputs in both mature and immature GC. Using both pharmacologic and optogenetic tools combined with electrophysiological recordings, we observed that in presence of cholinergic activation, mature neurons increase their spiking response to stimulation of medial perforant path (mPP) inputs, whereas no significant changes were seen for immature 4 week old neurons. Then we recorded from individual neurons in a whole cell configuration, isolating the evoked excitatory and inhibitory currents (EPSCs and IPSCs) in response to mPP stimulation. We observed that Ach induced a reduction in the inhibitory component of the response, which was more prominent for mature neurons. This produced an increase in the excitation to inhibition balance that explained the differential spiking response. In addition, we observed that activating mPP at high frequency, normally insufficient to produce long term potentiation (LTP) in control conditions, produce LTP when paired with optogenetic activation of cholinergic axons. We conclude that acetylcholine can provide a temporal window in which the information processing and plasticity rules of granule cells change, possibly allowing this brain region to adapt the encoding to the behavioral demands.