Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge.
In adult female rats, robust hippocampal changes occur when estradiol rises on the morning of proestrus. Whether estradiol mediates these changes, however, remains unknown. To address this issue, we used sequential injections of estradiol to simulate two key components of the preovulatory surge: the rapid rise in estradiol on proestrous morning, and the slower rise during the preceding day, diestrus 2. Animals were examined mid-morning of simulated proestrus, and compared to vehicle-treated or intact rats. In both simulated and intact rats, CA1-evoked responses were potentiated in hippocampal slices, and presynaptic mechanisms appeared to contribute. In CA3, multiple population spikes were evoked in response to mossy fiber stimuli, and expression of brain-derived neurotrophic factor was increased. Simulation of proestrous morning also improved performance on object and place recognition tests, in comparison to vehicle treatment. Surprisingly, effects on CA1-evoked responses showed a dependence on estradiol during simulated diestrus 2, as well as a dependence on proestrous morning. Increasing estradiol above the physiological range on proestrous morning paradoxically decreased evoked responses in CA1. However, CA3 pyramidal cell activity increased further, and became synchronized. Together, the results confirm that physiological estradiol levels are sufficient to profoundly affect hippocampal function. In addition: (i) changes on proestrous morning appear to depend on slow increases in estradiol during the preceding day; (ii) effects are extremely sensitive to the peak serum level on proestrous morning; and (iii) there are striking subfield differences within the hippocampus.
Scharfman
Helen E
HE
Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, NY 10962, USA. hscharfman@nki.rfmh.org
Hintz
Tana M
TM
Gomez
Juan
J
Stormes
Kerry A
KA
Barouk
Sharon
S
Malthankar-Phatak
Gauri H
GH
McCloskey
Daniel P
DP
Luine
Victoria N
VN
Maclusky
Neil J
NJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D004031:Diestrus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010052:Ovariectomy; D010060:Ovulation / Q000187:drug effects / Q000502:physiology*; D011359:Proestrus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013995:Time
D019208:Brain-Derived Neurotrophic Factor; D004958:Estradiol