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Effect of Corticosterone on Hippocampal Synaptic Plasticity and Voltage-dependent Calcium Channel on the Membrane of Hippocampal Neurons

Contact Person: Jian-zheng Zhou (zhoujz@nic.bmi.ac.cn)


Glucocorticoids are series of important steroid hormones in regulating metabolism of fat, protein and glucose in various peripheral tissues. Recent studies indicated that high concentration of glucocorticoids showed adverse effects on the central nervous system (CNS), especially on the hippocampus. It was reported that application of CORT in vitro not only impaired the primary cultured hippocampal neurons directly but also exacerbated neurotoxicity of some excitotoxins to hippocampal neurons. In addition, administration of corticosterone (CORT) to rats for three months led to significant impairment of learning and memory.

Long-term potentiation (LTP) is an electrophysiological phenomenon, and both the amplitude of population spike (PS) and slope of excitatory postsynaptic potential (EPSP) are persistently augmented when LTP is established. Large amount of evidences demonstrated that LTP of an evoked potential in the hippocampal dentate gyrus is one of the manifestation of synaptic plasticity and transmission. LTP is considered to be a synaptic model of learning and memory, though its relationship with learning and memory has not been completely elucidated. It was reported that synaptic plasticity in the hippocampus showed a good relationship with the performance in shuttle box test in rats. Rats with an inborn inferior performance required a greater threshold to generate LTP in comparison to rats with an inborn superior performance in shuttle box test. It has been presumed that LTP consisted of several phases, including induction phase, early maintenance phase and late maintenance phase and different phases were mediated by different mechanisms. It was found that LTP induction required the transient elevation of intracellular Ca2+ level and injection of Ca2+ chelator, EGTA or BAPTA or Ca2+ channel antagonist, nifedipine to postsynapse of hippocampal neurons blocked the formation of LTP, suggesting the importance of the cytosolic Ca2+ in LTP induction phase. It was reported that adrenalectomy of rat significantly reduced the amplitude of Ca2+-dependent-K+-mediated afterhyperpolarization (AHP) and supplemented with CORT to adrenalectomized rats restored the amplitude of AHP. Because the AHP amplitude directly reflects the cytosolic free Ca2+ level at the end of action potential, it seemed that CORT could affect the homeostasis of cytosolic free Ca2+ level in the hippocampal neurons. Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) was one of the main pathways for elevation of cytosoilc free Ca2+ level. In the present paper, effects of CORT on the formation of LTP as well as Ca2+ influx through VDCC were investigated.

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Zhou, JZ; Zhang, YX; Zheng, JQ; Zhou, JH; (1998). Effect of Corticosterone on Hippocampal Synaptic Plasticity and Voltage-dependent Calcium Channel on the Membrane of Hippocampal Neurons. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/
© 1998 Author(s) Hold Copyright