Long-term increases in the evoked population spike in the CA1 region of rat hippocampus induced by β-adrenergic receptor activation

Abstract

The effects of the selective β-adrenergic receptor agonist isoproterenol (ISO) were characterized in the CA1 region of the rat hippocampal slice preparation. As has been previously described, 500 nM ISO increased the amplitude of the evoked population spike response without having any effect upon field EPSP (fEPSP) responses. However, the increase in the population spike response was quite persistent and was not reversed by >30 min of washout in the majority of the slices tested; we have termed this prolonged increase β-adrenergic potentiation (BAP). As with the acute effect of ISO, BAP is confined to an increase in the population spike response and not the fEPSP. In input-output curves, this was clearly observed as a persistent leftward shift in the EPSP-population spike relationship. Similar long-term increases in the population spike could also be elicited by superfusion of the slices for 10 min with 20-25 μM norepinephrine (NE). Although both the acute and the long-term effects of ISO were blocked by pretreatment with timolol, a β-adrenergic antagonist, the long-term effects were not reversed by superfusion with timolol following ISO treatment, demonstrating that the prolonged effects were not due to slow washout of ISO from the tissue. BAP was not blocked by pretreatment with 50 μM 2-amino-5-phosphonovaleric acid, an NMDA receptor antagonist that blocks hippocampal long-term potentiation and the long-lasting changes in synaptic responses induced in the dentate gyrus by NE and ISO. These experiments demonstrate that NE can induce a novel and long-lasting increase in the excitability of the pyramidal neurons of the CA1 region following relatively brief activation of β-adrenergic receptors, and that this response is distinct from the other long-lasting effects that have been described in other regions.