The brainstem locus coeruleus (LC) is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline (NA) is a neuromodulator involved in the regulation of excitability of brain networks. In this study, we investigated whether chemogenetic activation of the LC is able to induce hippocampal noradrenaline release and affects hippocampal excitability.Male Sprague Dawley rats (n=8) were injected with the viral vector CAV2-PRSx8-hM3Dq in the LC for expression of hM3Dq, which allows chemogenetic LC activation upon systemic injection with deschloroclozapine (DCZ). Rats were also injected with AAV9-hSyn-NE2m-mRuby3 in the hippocampus for expression of the GRABNE2m biosensor, which allows to measure LC-induced hippocampal NA changes by measuring fluorescence changes when NA binds to the α2-adrenoceptor that is coupled to a GFP. Rats were implanted with a stimulation electrode in the perforant path and a recording optrode to record dentate gyrus (DG) evoked potentials (EP) and changes in GRABNE2m fluorescence.Injection of DCZ resulted in a significant increase in hippocampal NA (ΔF/F, 2.65 ± 0.57%, p<0.05) and in DG population spike (PS) amplitude (change from baseline, 45.24 ± 29.81%, p<0.05) . The EP slope was not changed. Changes in PS amplitude correlated significantly with NA changes (p<0.01, figure).This study demonstrated a significant increase in hippocampal NA which resulted in a significant increase in hippocampal excitability. By means of GRAB-sensor technology, this research was the first to measure hippocampal NA changes, induced by chemogenetic activation of the LC, with high temporal resolution and specificity.