RT Journal Article
SR Electronic
T1 Ovarian Hormone Loss Impairs Excitatory Synaptic Transmission at Hippocampal CA3–CA1 Synapses
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 16158
OP 16169
DO 10.1523/JNEUROSCI.2001-13.2013
VO 33
IS 41
A1 Wendy W. Wu
A1 Damani N. Bryant
A1 Daniel M. Dorsa
A1 John P. Adelman
A1 James Maylie
YR 2013
UL http://www.jneurosci.org/content/33/41/16158.abstract
AB Premature and long-term ovarian hormone loss following ovariectomy (OVX) is associated with cognitive impairment. This condition is prevented by estradiol (E2) therapy when initiated shortly following OVX but not after substantial delay. To determine whether these clinical findings are correlated with changes in synaptic functions, we used adult OVX rats to evaluate the consequences of short-term (7–10 d, OVXControl) and long-term (∼5 months, OVXLT) ovarian hormone loss, as well as subsequent in vivo E2 treatment, on excitatory synaptic transmission at the hippocampal CA3–CA1 synapses important for learning and memory. The results show that ovarian hormone loss was associated with a marked decrease in synaptic strength. E2 treatment increased synaptic strength in OVXControl but not OVXLT rats, demonstrating a change in the efficacy for E2 5 months following OVX. E2 also had a more rapid effect: within minutes of bath application, E2 acutely increased synaptic strength in all groups except OVXLT rats that did not receive in vivo E2 treatment. E2's acute effect was mediated postsynaptically, and required Ca2+ influx through the voltage-gated Ca2+ channels. Despite E2's acute effect, synaptic strength of OVXLT rats remained significantly lower than that of OVXControl rats. Thus, changes in CA3–CA1 synaptic transmission associated with ovarian hormone loss cannot be fully reversed with delayed E2 treatment. Given that synaptic strength at CA3–CA1 synapses is related to the ability to learn hippocampus-dependent tasks, these findings provide additional insights for understanding cognitive impairment-associated long-term ovarian hormone loss and ineffectiveness for delayed E2 treatment to maintain cognitive functions.