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The Journal of Neurophysiology Vol. 84 No. 4 October 2000, pp. 1800-1808
Copyright ©2000 by the American Physiological Society
Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia 22908
Zamani, M. Reza,
Nancy L Desmond, and
William B Levy.
Estradiol Modulates Long-Term Synaptic Depression in Female Rat
Hippocampus. J. Neurophysiol. 84: 1800-1808, 2000. Fluctuating estradiol levels in the adult, female
rat modify the anatomical and functional organization of the
hippocampal CA1 region. When systemic levels of estradiol are low,
e.g., on estrus or in ovariectomized (OVX) rats, long-term synaptic
potentiation is difficult to induce in vivo. However, little is known
about the role of this ovarian hormone in long-term synaptic
depression. Using multiple conditioning paradigms, we assess the
magnitude of long-term depression (LTD) at CA3-CA1 synapses in vitro
from adult, ovariectomized rats as a function of systemic estradiol replacement. In hippocampal slices from control OVX rats with low
levels of estradiol, a low-frequency (2 Hz), asynchronous conditioning
stimulation protocol does not produce LTD at 1 h postconditioning.
However, this same protocol induces robust LTD in slices from
estradiol-treated OVX rats. When the conditioning frequency is
increased to 4 Hz, slices from both groups of rats show robust LTD in
vitro. At an even higher conditioning frequency (10 Hz), the 2-Hz-based
observations are reversed; no consistent changes in synaptic
transmission are observed in slices from estradiol-treated OVX rats,
but those from control rats (OVX + oil) show robust LTD. Thus estradiol
reduces the frequency threshold for LTD induction at the CA3-CA1
synapses. Further, regardless of the conditioning frequency employed,
where robust LTD is seen, its induction depends on normally functioning
N-methyl-D-aspartate (NMDA) receptors during
conditioning. The shift in conditioning frequency needed to elicit LTD
is consistent with a decrease in NMDA receptor activation with
decreasing estradiol levels.
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