Glutamatergic activation of locus coeruleus induces selective noradrenergic modulation of medial and lateral perforant path evoked potentials in the dentate gyrus of the anaesthetized rat

Norepinephrine (NE) induces long-lasting potentiation of the medial perforant path (PP) and depression of the lateral PP input to dentate gyrus (DO) in vitro. In vivo, nucleus paragigantocellularis stimulation transiently potentiates the medial PP evoked population spike and depresses a lateral PP mediated synaptic potential in DO following locus coeruleus (LC) activation. In contrast, using glutamatergic activation of LC, this study in one experiment observed the expected potentiation of medial PP input to DO, but no depression of the lateral PP evoked potential (LOT stimulation, 60 s ISI) in DO post activation. A second experiment (10 s ISI) demonstrated significant potentiation of the lateral PP input to DO for 30 min immediately following LC activation, but no potentiation of the medial PP input. These results contrast with previous NE-induced in vitro and in vivo modulation of the lateral and medial PP, but resemble the long-term heterosynaptic interactions observed with tetanic stimulation of the medial and lateral PP, suggesting a competitive relationship between the medial and lateral PP inputs to DO in which the input paired most strongly and consistently with elevated LC-NE levels in the hippocampus controls the network.