Estrogen-Mediated Structural and Functional Synaptic Plasticity in the Female Rat Hippocampus

doi:10.1006/hbeh.1998.1466

Hormones and Behavior

Volume 34, Issue 2, October 1998, Pages 140-148

https://doi.org/10.1006/hbeh.1998.1466 Get rights and content

Abstract

Light and electron microscopic studies have shown that ovarian steroids regulate the density and number of excitatory synaptic inputs to hippocampal pyramidal cells in the adult female rat; elevated levels of estradiol are associated with a higher density of dendritic spine synapses on CA1 pyramidal cells. Electrophysiological analyses indicate that these hormone-induced synapses increase hippocampal excitability as well as the potential for synaptic plasticity. Importantly, correlation of dendritic spine density and sensitivity to synaptic input of individual CA1 pyramidal cells from estradiol-treated and control animals suggests that synapses induced by estradiol may be a specialized subpopulation that contains primarily the NMDA subtype of glutamate receptor. The apparent NMDA receptor specificity of these synapses may be key to understanding their functional significance. Currently, the behavioral consequences of additional spine synapses are unknown. Numerous studies have aimed at correlating hormone-induced changes in hippocampal connectivity with differences in hippocampus-dependent spatial learning ability in mazes, but the results of these efforts have been equivocal. Anatomical, electrophysiological, and behavioral studies of estradiol-mediated hippocampal plasticity are reviewed. In conclusion, it is suggested that standard behavioral tests of hippocampal function are not sufficient to reveal the behavioral consequences of hormone-induced hippocampal plasticity. Rather, understanding the behavioral consequences of estradiol and progesterone effects on hippocampal connectivity may require analysis of the hippocampus' cognitive and spatial information processing functions in relation to alternative biologically relevant behaviors. A (nonexclusive) proposal that hormone-induced hippocampal plasticity may facilitate appropriate prepartum/maternal behavior is discussed.

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Accumulating evidence suggests that estrogens play an important modulatory role in the pathogenesis of psychosis. Estrogens come online within a dynamic developmental context of emerging psychopathology and neurodevelopment. As a result, estradiol (the primary form of estrogen) may influence psychosis lability directly or indirectly through its neurodevelopmental influence on estrogens-sensitive areas like the hippocampus. Understanding this influence may provide novel insight into mechanisms of psychosis lability. This study included baseline and year 2 timepoints from 4422 female participants from the Adolescent Brain Cognitive Development (ABCD) study (age 8–13), who varied in estradiol availability (pre-menarche, post-menarche, pre- and post-menarche timepoints). Estradiol availability was related to psychotic-like experiences (PLE) severity both directly and as an interactive effect with hippocampal connectivity using menarche status (pre/post) in a multilevel model. PLE severity was highest in individuals with early menarche emphasizing the importance of the developmental timing. Although PLE severity decreased over time in the sample, it stayed clinically-relevant over 2 years. Lower hippocampal connectivity was related to elevated PLE severity. This effect was moderated by estradiol; before the availability of estradiol (pre-menarche), lower hippocampal connectivity significantly contributed to the PLE severity, but when estradiol was available (post-menarche) hippocampal dysconnectivity did not account for PLE severity. This moderation suggests that the estrodiol’s influence on hippocampal plasticity also reduced the mechanistic role of the hippocampus on PLE severity. Further, the lack of a significant direct reduction of PLE severity post-menarche, may suggest an increased role for other interacting psychosis lability factors during this critical developmental period.
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^☆: B. E. EleftheriouR. L. Sprott

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Regular ArticleEstrogen-Mediated Structural and Functional Synaptic Plasticity in the Female Rat Hippocampus☆

Abstract

Exp. Neurol.

Brain Res.

Trends Pharmacol.

Brain Res.

Horm. Behav.

Horm. Behav.

Neuron

Neurosci. Lett.

Brain Res.

Brain Res.

Neuroscience

Neurobiol. Learning Memory

Brain Res.

Neurobiol. Learning Memory

Pharmacol. Biochem. Behav.

Physiol. Behav.

Brain Res.

NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus

Nature

Spatial learning and memory at defined points of the estrous cycle: Effects on performance of a hippocampal dependent task

Behav. Neurosci.

Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path

J. Physiol.

Estrogen-induced changes in synaptic morphology in the midbrain central gray

Exp. Brain Res.

Ovarian steroidal control of connectivity in the female hippocampus: An overview of recent experimental findings and speculation on its functional consequences

Hippocampus

Long-term potentiation and functional synapse induction in developing hippocampus

Nature

Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons

Neuroendocrinology

Regular Article
Estrogen-Mediated Structural and Functional Synaptic Plasticity in the Female Rat Hippocampus☆