Change in bi-directional plasticity at CA1 synapses in hippocampal slices taken from 6-hydroxydopamine-treated rats: the role of endogenous norepinephrine.
The object of the present study is to investigate the role of endogenous adrenergic innervation in regulating bi-directional synaptic plasticity in rat hippocampal CA1 synapses. The endogenous adrenergic system was eliminated by giving subcutaneous injection of 6-hydroxydopamine (6-OHDA) to rats immediately after birth, and the animals were killed for experiments at postnatal ages of 25-35 days. In hippocampal slices taken from 6-OHDA-treated animals, theta-burst stimulation at 100 Hz failed to induce long-term potentiation (LTP) at CA1 synapses. However, the induction of long-term depression (LTD) by prolonged low frequency stimulation at 1 Hz was unaffected in slices from 6-OHDA-treated animals. Bath application of norepinephrine (NE) restored LTP to control levels and blocked LTD. This effect was mimicked by beta- but not alpha-adrenergic receptor agonists, i.e. by isoproterenol but not phenylephrine. The activators of adenylyl cyclase and protein kinase A (PKA), i.e. forskolin and 8-bromoadenosine-3', 5'-cyclic monophosphate, respectively, restored LTP in slices from 6-OHDA-treated animals. In addition, application of the D1/D5 receptor agonist, dihydrexidine, also restored LTP in slices from 6-OHDA-treated animals. These results suggest that physiologically the recruitment of catecholamine innervation may be important for induction of LTP at hippocampal CA1 synapses during tetanic stimulation, while it may not be essential for LTD induction by prolonged 1 Hz stimulation. The released NE and dopamine exert their role in modulating synaptic plasticity via activation of beta-adrenergic and D1/D5 receptors, respectively, which in turn increase the levels of cytoplasm adenosine-3',5'-cyclic monophosphate and PKA.
Yang
Hsiu-Wen
HW
Department of Physiology, Chinese Medical College, Taichung 404, Taiwan.
Lin
Yi-Wen
YW
Yen
Chia-De
CD
Min
Ming-Yuan
MY
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008125:Locus Coeruleus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D018491:Dopamine Agonists; D016627:Oxidopamine; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine