Cyclical changes in endogenous levels of oestrogen modulate the induction of LTD and LTP in the hippocampal CA1 region

Good, Mark Andrew; Day, Mark L.; Muir, Janice L.

doi:10.1046/j.1460-9568.1999.00920.x

Cited by 135 publications

(102 citation statements)

References 39 publications

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“…This finding fits well with our previous results showing that estrogen, by activating the MAP kinase pathway and by increasing the state of tyrosine phosphorylation of NR2 subunits of NMDA receptors, produced an increase in the magnitude of LTP in hippocampal slices (15). It is also consistent with reports indicating facilitation of LTP induction by estrogen in ovariectomized female rats (24), increased LTP in the afternoon of proestrus of female rats (25), and increased LTP magnitude in proestrus as compared with diestrus in CA1 of adult female rats (26). Therefore, we propose that circulating levels of estrogen regulate the phosphorylation͞ activation state of ERK2.…”

Section: Discussionsupporting

confidence: 90%

Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway

Foy

Vouimba³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

181

124

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Hippocampal synaptic structure and function exhibit marked variations during the estrus cycle of female rats. Estradiol activates the mitogen-activated protein (MAP) kinase pathway in numerous cell types, and MAP kinase has been shown to play a critical role in the mechanisms underlying synaptic plasticity. Here, we report that endogenous estrogen produces a tonic phosphorylation͞activa-tion of extracellular signal-regulated kinase 2 (ERK2)͞MAP kinase throughout the female rat brain and an increase in tyrosine phosphorylation of NR2 subunits of N-methyl-D-aspartate (NMDA) receptors. Moreover, cyclic changes in estrogen levels during the estrus cycle of female rats are associated with corresponding changes in the levels of activation of ERK2, the state of tyrosine phosphorylation of NR2 subunits of NMDA receptors, and the magnitude of long-term potentiation in hippocampus. Thus, cyclic changes in female sexual hormones result in marked variations in the state of activation of a major cellular signaling pathway critical for learning and memory and in a cellular model of learning and memory.E strogens have profound effects on hippocampal structure and physiology (1-4) and on hippocampal-dependent learning and memory (5, 6). In particular, estrogens have been shown to increase the density of dendritic spines on CA1 pyramidal neurons (7). In hippocampal slices, 17␤-estradiol increases electrophysiological responses elicited by activation of both ␣-amino-3-hydroxy-5-methylisoxazole propionic acid and N-methyl-Daspartate (NMDA) receptors and the magnitude of long-term potentiation (LTP) in field CA1 (8, 9). At the cellular level, numerous laboratories have shown that, in addition to direct genomic effects, 17␤-estradiol activates the extracellular regulated kinase͞mitogen-activated protein (ERK͞MAP) kinase pathway (10-12), an effect associated with the neurotrophic͞ neuroprotective actions of estrogen (13,14). We recently reported that estrogen-mediated activation of the ERK͞MAP kinase pathway in hippocampus was involved in the rapid effects of estrogen on NMDA receptors and LTP through tyrosine phosphorylation of NR2 subunits of NMDA receptors (15).The ERK͞MAP kinase pathway is a central cellular signaling pathway linking numerous extracellular signals to membrane receptors, transcription factors, and gene regulation (16) and is critically involved in synaptic plasticity, learning, and memory (17)(18)(19)(20). Pharmacological manipulations directed at blocking this pathway have consistently produced impairment in synaptic plasticity, learning, and memory, and this pathway is activated with LTP-inducing tetanus or in different learning paradigms. The present study analyzed whether endogenous estrogen regulates the state of activation of the ERK͞MAP kinase pathway and whether cyclic variations in estrogen levels during the female estrus cycle suffice to modify this pathway in the brain. Moreover, we determined the state of tyrosine phosphorylation of NMDA-receptor subunits, as well as the magnitude of LTP in field CA1 o...

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Section: Discussionsupporting

confidence: 90%

Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway

Foy

Vouimba³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

181

124

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“…E2 also improves other forms of memory formation such as spatial reference memory and trace conditioning controlled by the hippocampus and forms of visual memory and strategy solving tasks controlled by the cerebral cortex (Frick et al, 2002;Luine et al, 2003;Leuner et al, 2004;Rhodes and Frye, 2004). In the hippocampus, E2 has also been shown to facilitate the formation of new synapses (Woolley and McEwen, 1993) and to exert a positive impact on induction of LTP (Cordoba Montoya and Carrer, 1997;Good et al, 1999;Vouimba et al, 2000). Thus, although short-term potentiating mechanisms such as those mediated by levels of calcium concentration and activation of kinases and phosphatases can vary substantially between hippocampal and cerebellar learning (Cordoba Montoya and Carrer, 1997;Good et al, 1999;Vouimba et al, 2000), sex hormone-related mechanisms appear to be able to overrule these differences and exert general effects in different brain regions.…”

Section: Discussionmentioning

confidence: 99%

“…The gonadal hormone estradiol (E2) has beneficial effects on the formation of hippocampus-dependent memory (Farr et al, 1995;O'Neal et al, 1996;Gibbs et al, 1998;Shors et al, 1998;Leuner et al, 2004;Rhodes and Frye, 2004). During the estrous cycle, pyramidal cells in the hippocampus are subject to major changes including morphological changes (Woolley and McEwen, 1993;Adams et al, 2001) and modifications in synaptic efficacy (Warren et al, 1995;Cordoba Montoya and Carrer, 1997;Good et al, 1999;Vouimba et al, 2000;Mukai et al, 2007). Yet, it is not known whether E2 also affects cerebellar memory formation, despite the prominent presence of estrogen receptors (ERs) in the cerebellum (Shughrue et al, 1997;Price and Handa, 2000).…”

Section: Introductionmentioning

confidence: 99%

Estradiol Improves Cerebellar Memory Formation by Activating Estrogen Receptor β

Andreescu¹,

Milojkovic²,

Haasdijk³

et al. 2007

J. Neurosci.

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Learning motor skills is critical for motor abilities such as driving a car or playing piano. The speed at which we learn those skills is subject to many factors. Yet, it is not known to what extent gonadal hormones can affect the achievement of accurate movements in time and space. Here we demonstrate via different lines of evidence that estradiol promotes plasticity in the cerebellar cortex underlying motor learning. First, we show that estradiol enhances induction of long-term potentiation at the parallel fiber to Purkinje cell synapse, whereas it does not affect long-term depression; second, we show that estradiol activation of estrogen receptor ␤ receptors in Purkinje cells significantly improves gain-decrease adaptation of the vestibulo-ocular reflex, whereas it does not affect general eye movement performance; and third, we show that estradiol increases the density of parallel fiber to Purkinje cell synapses, whereas it does not affect the density of climbing fiber synapses. We conclude that estradiol can improve motor skills by potentiating cerebellar plasticity and synapse formation. These processes may be advantageous during periods of high estradiol levels of the estrous cycle or pregnancy.

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“…For example, in diestrus mice, the antinociceptive and proconvulsant effects of morphine are stronger than those in estrus mice, whereas the reverse is true for its anticonvulsant effect. Both GABAergic and N-methyl-D-aspartate (NMDA)-receptor mechanisms are subject to estrus-cycle variations (36,(58)(59)(60) and provide possible substrates for opioid-sex hormone interactions in the modulation of seizure susceptibility. Moreover, the regulatory interactions between sex hormones and endogenous opioids with anticonvulsant activity, like dynorphin, also may contribute to variations in response to morphine (25,61).…”

Section: Discussionmentioning

confidence: 99%

Sex and Estrus Cycle Differences in the Modulatory Effects of Morphine on Seizure Susceptibility in Mice

et al. 2004

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Summary:Purpose: To evaluate the effects of sex and estrus cycle on biphasic anticonvulsant and proconvulsant modulation of seizure threshold by morphine.Methods: The threshold for the clonic seizures (CST) induced by acute intravenous administration of γ -aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice. Estrus cycle was assessed by vaginal smears. The effect of removing circulating sex hormones was assessed by gonadectomy.Results: At baseline, diestrus females had a higher CST compared with males and estrus females. Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect. Morphine at higher doses (30 and 60 mg/kg) significantly decreased CST in males and diestrus females, with less relative effect in estrus mice. In both phases, morphine exerted stronger effects in males compared with females. Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine.Conclusions: The biphasic modulation of seizure threshold is subject to both constitutive sex differences in sensitivity to morphine and hormonal fluctuations during the estrus cycle.

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Cyclical changes in endogenous levels of oestrogen modulate the induction of LTD and LTP in the hippocampal CA1 region

Cited by 135 publications

References 39 publications

Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway

Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway

Estradiol Improves Cerebellar Memory Formation by Activating Estrogen Receptor β

Sex and Estrus Cycle Differences in the Modulatory Effects of Morphine on Seizure Susceptibility in Mice

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