PRESYNAPTIC ENHANCEMENT OF EXCITATORY SYNAPTIC TRANSMISSION BY BETA-ADRENERGIC-RECEPTOR ACTIVATION

1. Previous studies have shown that beta-adrenergic receptor activatio n has many effects on neuronal function in hippocampal area CA1. Howev er, all of the physiological effects of beta-adrenergic receptor activ ation in this region reported to date have been attributed to postsyna ptic mechanisms. A series of studies was performed to test the hypothe sis that beta-adrenergic receptor activation also acts presynaptically to enhance excitatory synaptic transmission. 2. Application of the se lective beta-adrenergic agonist isoproterenol to hippocampal slices in duced an increase in the amplitude of evoked excitatory postsynaptic c urrents (EPSCs) in CA1 pyramidal cells. This response was potentiated in the presence of a cyclic nucleotide phosphodiesterase inhibitor. Is oproterenol also resulted in the appearance of a late inward synaptic current that likely represents polysynaptically evoked EPSCs. Both the increased amplitude of the monosynaptic EPSC and the appearance of po lysynaptic EPSCs in response to isoproterenol were blocked by H89, an inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pro tein kinase. 3. Isoproterenol induced an increase in the frequency of spontaneous miniature EPSCs but did not affect the amplitude of these currents. In addition, isoproterenol had no effect on currents elicite d by direct application of the ionotropic glutamate receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazol-4-propionic acid (AMPA). 4. The se results suggest that activation of presynaptic beta-adrenergic rece ptors enhances synaptic transmission in area CA1 via activation of cAM P-dependent protein kinase.