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The Journal of Neuroscience, May 15, 2003, 23(10):4173-4181

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Enhancement of Associative Long-Term Potentiation by Activation of -Adrenergic Receptors at CA1 Synapses in Rat Hippocampal Slices

Yi-Wen Lin,^1,3 Ming-Yuan Min,¹ Tsai-Hsien Chiu,³ and Hsiu-Wen Yang²

¹Department of Physiology, Chinese Medical College, Taichung, 404, Taiwan, ²Department of Life Sciences, Chung Shan Medical University, Taichung, 402, Taiwan, and ³Department of Physiology, National Yang Ming University, Taipei, 112, Taiwan

The objective of this study was to evaluate the role of -adrenergic receptors in modulating associative long-term potentiation (LTP) induced at CA1 synapses. Two independent Schaffer collateral pathways were stimulated in hippocampal slices. The field EPSP (fEPSP) response evoked in one pathway (the weak pathway) was small, whereas a large response, usually 80–90% of the maximum, was evoked in the strong pathway. After recording of the baseline fEPSP evoked at 0.033 Hz, LTP of the weak pathway could be associatively induced by paired stimulation of the weak and strong pathways 100 times at 6 sec intervals, with stimulation of the weak pathway preceded 3–10 msec. However, pairing protocols with an interval between stimulation of the two pathways >10 msec resulted in no LTP. The induced LTP was NMDA receptor dependent, because 50 µM D,L-APV blocked its induction. Bath application of 1 µM isoproterenol enhanced LTP by increasing the window of the stimulation interval up to 15 msec but did not affect the magnitude of the LTP induced by pairing protocols with intervals <10 msec. Similar results were obtained when the experiments were repeated using whole-cell recording. These results suggest that activation of -adrenergic receptors can enhance associative LTP by increasing the width of the time window rather than the magnitude of the LTP. Enhancement of LTP by -adrenergic receptors was blocked in slices by pretreatment with inhibitors of protein kinase A or mitogen-activated protein kinase, suggesting that these signaling cascades are involved in this process.

Key words: associative LTD; associative LTP; -adrenergic receptors; hippocampus; isoproterenol; synaptic plasticity

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Received Oct. 11, 2002; revised Feb. 21, 2003; accepted Mar. 5, 2003.

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