PATHWAY SPECIFICITY OF NORADRENERGIC PLASTICITY IN THE DENTATE GYRUS

Previous experiments have described highly specific effects of noradre nergic agonists on synaptic transmission in the dentate gyrus (DG). Fo r example, perfusion of hippocampal slices with the beta-noradrenergic agonist isoproterenol induces a long-lasting potentiation (LLP) of ex tracellularly recorded responses following stimulation of the medial p erforant path (PP), and longlasting depression (LLD) of responses evok ed by stimulation of the lateral PP (Dahl D, Sarvey JM, 1989, Proc Nat l Acad Sci USA 86:4776-4780). To examine the possible interactions of LLP, LLD, and long-term potentiation induced by tetanic stimulation (L TP), the authors recorded extracellular field potentials evoked in the DG by stimulation of the lateral or medial perforant path following L TP and LLP or LLD, invoked in different orders. After establishment of LLP or LLD by bath application of isoproterenol, subsequent tetanizat ion of the respective afferents resulted in additional potentiation of the medial PP-evoked response and return of the lateral PP-evoked res ponse to baseline levels. In other slices: application of isoprotereno l after establishment of LTP resulted in further potentiation of media l PP-evoked responses but no change in the potentiated response evoked by lateral PP stimulation. Thus the pathway specificity was maintaine d irrespective of the history of previous potentiation or depression. Experiments using the specific beta(1) antagonist metoprolol further c onfirmed pathway specificity. Perfusion with 20 mu M of metoprolol app eared to reduce LTP evoked by stimulation of the medial but not latera l PP. In a subsequent experiment, metoproloI in the absence of tetaniz ation produced LLD of the medial PP-evoked response and LLP of the lat eral PP-evoked response, opposite to the effects of ISO. These results confirm the impressive extent of pathway specificity in the DG and re veal the persistent capacity for synaptic modification as exemplified by the processes of LLP, LLD, and LTP. (C) 1994 Wiley-Liss, Inc.