Inhibition of associative long-term depression by activation of beta-adrenergic receptors in rat hippocampal CA1 synapses.
The aim of this study was to investigate the role of beta-adrenergic receptors in modulating associative long-term depression (LTD) at CA1 synapses in rat hippocampal slices. Standard extracellular electrophysiological techniques were employed to record field excitatory post-synaptic potential (fEPSP) activity and to induce associative LTD. Two independent Schaffer collateral pathways were elicited in hippocampal CA1 areas. In one (weak) pathway, the stimulating intensity was adjusted to elicit small fEPSP activity (20-30% of the maximum response). In contrast, 80-90% of the maximum response was evoked in the other (strong) pathway. Associative LTD of weak pathway could be induced by paired stimulation of weak and the strong pathways, repeated 100 times at 0.167 Hz. The associative LTD of weak pathway was NMDA receptor- and phosphatase 2B dependent, because bath application of 50 microM D, L-AP5 or 10 microM cypermethrin blocked its induction. Bath application of 1 microM isoproterenol inhibited associative LTD, and this effect was blocked by timolol, suggesting the involvement of beta-adrenergic receptors. The inhibitory effect of beta-adrenergic receptors on LTD induction was blocked in slices pretreated with inhibitors of protein kinase A and mitogen-activated protein kinase, suggesting that these signal cascades are downstream effectors following activation of beta-adrenergic receptors. Nevertheless, bath application of timolol or cypermethrin alone did not have significant effect on associative LTD induction, suggesting neither endogenous function of beta-adrenergic receptor nor endogenous PKA activity does have a role in associative LTD induction.
Lin
Yi-Wen
YW
Institute of Biomedical Science, Academia Sinica, Taipei, 115, Taiwan, yiwenlin@ibms.sinica.edu.tw
Yang
Hsiu-Wen
HW
Min
Ming-Yuan
MY
Chiu
Tsai-Hsien
TH
D000818:Animals; D019703:Calcineurin / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System; D011722:Pyrethrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013999:Timolol / Q000494:pharmacology
D011722:Pyrethrins; D011943:Receptors, Adrenergic, beta; D016194:Receptors, N-Methyl-D-Aspartate; C017160:cypermethrin; D013999:Timolol; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D007545:Isoproterenol