Estradiol rapidly modulates synaptic plasticity of hippocampal neurons: Involvement of kinase networks

Hasegawa, Yoshitaka; Hojo, Yasushi; Kojima, Hiroki; Ikeda, Motoko; Hotta, Keisuke; Sato, Rei; Ooishi, Yuuki; Yoshiya, Miyuki; Chung, Bon Chu; Yamazaki, Takeshi; Kawato, Suguru

doi:10.1016/j.brainres.2014.12.056

Cited by 85 publications

(100 citation statements)

References 88 publications

(130 reference statements)

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“…Some data support the conclusion that input from the basal forebrain is necessary for estradiol to enhance spines in adult female rats (Leranth et al 2000). However, bathapplied E 2 can increase spines in male hippocampal slices (Mukai et al 2007;Murakami et al 2014;Hasegawa et al 2015) and cultured embryonic hippocampal neurons (Murphy and Segal 1996), suggesting that subcortical input may not be essential, at least in an ex vivo system. Other work shows that two injections of estradiol benzoate spaced 24 h apart failed to increase CA1 spine synapse density in ovariectomized rats trained in the Morris water maze , indicating that stressful behavioral training may interfere with the effects of estradiol on CA1 spinogenesis.…”

Section: Spine Densitymentioning

confidence: 76%

“…As mentioned earlier, E 2 can rapidly phosphorylate several cellsignaling cascades, and this phosphorylation is associated with the ability of E 2 to increase CA1 dendritic spine density and LTP (Hasegawa et al 2015). Accordingly, many of these same cascades are necessary for E 2 to enhance memory consolidation.…”

Section: Cell Signalingmentioning

confidence: 81%

“…mTOR signaling can be activated by a host of upstream kinases including phosphatidylinositol 3-kinase (PI3K), Akt, and ERK (Richter and Klann 2009;Hoeffer and Klann 2010;Laplante and Sabatini 2012), and phosphorylation of many of these kinases has been implicated in the ability of E 2 to increase CA1 spine density in hippocampal slices from male rats. For example, the aforementioned E 2 -induced spine increase in male hippocampal slices was blocked by inhibitors of ERK, PI3K, protein kinase A (PKA), protein kinase C (PKC), and CaMKII (Hasegawa et al 2015). Inhibitors of these signaling cascades also prevented E 2 from augmenting u-bust-stimulated long-term potentiation (LTP) in male hippocampal slices (Hasegawa et al 2015), suggesting a key role for activation of these cell-signaling cascades in E 2 -induced synaptic potentiation.…”

Section: Spine Densitymentioning

confidence: 99%

“…For example, the aforementioned E 2 -induced spine increase in male hippocampal slices was blocked by inhibitors of ERK, PI3K, protein kinase A (PKA), protein kinase C (PKC), and CaMKII (Hasegawa et al 2015). Inhibitors of these signaling cascades also prevented E 2 from augmenting u-bust-stimulated long-term potentiation (LTP) in male hippocampal slices (Hasegawa et al 2015), suggesting a key role for activation of these cell-signaling cascades in E 2 -induced synaptic potentiation. Similarly, an E 2 -induced increase in cortical dendritic spine density observed 30 min after bath application in embryonic rat cultures was blocked by pharmacological inhibition of Rap/AF-6/ ERK signaling (Srivastava et al 2008).…”

Section: Spine Densitymentioning

confidence: 99%

“…mTOR signaling is essential for local protein synthesis within neurons (Hoeffer and Klann 2010), and hippocampal infusions of rapamycin impair consolidation of object recognition, contextual fear, and spatial memories (Dash et al 2006;Parsons et al 2006;Bekinschtein et al 2007;Myskiw et al 2008). As such, the regulation of mTOR signaling suggests a way in which E 2 may rapidly regulate protein synthesis and LTP in the hippocampus (Hasegawa et al 2015).…”

Section: Cell Signalingmentioning

confidence: 99%

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Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

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Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17b-estradiol (E 2 ), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E 2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E 2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E 2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs.Hormones have long been known to play key roles in regulating learning and memory. Many hormones, including epinephrine, glucocorticoids, and insulin influence learning and memory via inverted U-shaped dose-response relationships in which memory is enhanced by moderate, but not low or high, hormone levels (Roozendaal 2000;Korol and Gold 2007;McNay and Recknagel 2011). Research from the past two decades has demonstrated that sex steroid hormones, particularly the potent estrogen 17b-estradiol (E 2 ), also regulate learning and memory in male and female rodents via an inverted U-shaped dose-response function that is influenced by estrogen receptor expression (Packard and Teather 1997a;Packard 1998;Foster 2012). Yet E 2 has not gained widespread acceptance as a hormonal modulator of memory in both females and males, perhaps because the majority of this research has been conducted in female rodents. Moreover, the common view of E 2 as a "female" hormone may contribute to the misperception that E 2 is not relevant for cognitive function in males. However, considerable evidence supports a vital role for E 2 in mediating neural function and behavior in male rodents. Therefore, it is important for investigators working with males to understand the ways in which E 2 and other sex steroid hormones (e.g., androgens, progestins, and other estrogens) may influence their brain regions and behaviors of interest.Another reason for investigators to be cognizant of sex steroid hormone-induced regulation of learning and memory is that males and females may respond differently to various treatments and environmental factors. A classic example is that of acute stress, which enhances classical conditioning and increases apical CA1 dendritic spine density in male rats, but impairs classical conditioning and decreases CA1 spine density in female rats (Wood and Shors 1998;Shors et al. 2001). Therefore, investigators hoping to comply with National Institutes of Health policies that encourage the inclusion of females in biomedical research must be aware that adding females to a study is not as simple as adding another group. In some ways, females are fundamentally different from males, the most obvious of which is the presence of reproductive...

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Section: Spine Densitymentioning

confidence: 76%

Section: Cell Signalingmentioning

confidence: 81%

Section: Spine Densitymentioning

confidence: 99%

Section: Spine Densitymentioning

confidence: 99%

Section: Cell Signalingmentioning

confidence: 99%

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Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

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Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

Panichi

Dieni

Sullivan

et al. 2022

J of Comparative Neurology

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Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.

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Theta burst stimulation‐induced LTP: Differences and similarities between the dorsal and ventral CA1 hippocampal synapses

Kouvaros

Papatheodoropoulos

2016

Hippocampus

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The hippocampal synapses display a conspicuous ability for long-term plasticity, which is thought to contribute to learning and memory. Previous research has shown that long-term potentiation (LTP) greatly differs between the dorsal (DH) and ventral (VH) CA1 hippocampal synapses when induced by high-frequency stimulation. In this study, using rat hippocampal slices and more physiologically relevant activity patterns based on the frequency of the theta rhythm (i.e., theta-burst stimulation, TBS) we found that the DH compared with the VH displayed a higher ability for induction and stability of NMDA receptor-dependent LTP of the field excitatory postsynaptic potential. Nevertheless, the maximal magnitude of LTP was similar in the two hippocampal segments. Blockade of GABA receptors prevented the LTP induction by the minimal effective TBS and reduced the magnitude of LTP induced by longer TBS. TBS produced a three-fold higher facilitation of the synaptic burst responses in the DH compared with the VH, accompanied by a strong enhancement in the postsynaptic excitation in the DH but mostly depression in the VH. The DH displayed NMDA receptor-dependent and NMDA receptor-independent facilitation, but the facilitation in the VH was only NMDA receptor-dependent. Also, the TBS-associated activity of GABA receptors was higher in the DH than in the VH. The different response profiles during TBS could underlie the differences in LTP between the two hippocampal segments. L-type voltage-dependent calcium channels (L-VDCC) and the metabotropic glutamate receptor-5 (mGluR5) equally contributed in DH and VH to compound LTP induced by relatively long TBS. We propose that these dorsoventral differences in synaptic plasticity reflect specializations of the intrinsic circuitry of the hippocampus, that are involved in the distinct information processing performed by the two hippocampal segments and could effectively support the contribution of the dorsal and the ventral hippocampal segment to single event memory and to emotional memory respectively. © 2016 Wiley Periodicals, Inc.

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Estradiol rapidly modulates synaptic plasticity of hippocampal neurons: Involvement of kinase networks

Cited by 85 publications

References 88 publications

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Inhibition of androgenic pathway impairs encoding of cerebellar‐dependent motor learning in male rats

Theta burst stimulation‐induced LTP: Differences and similarities between the dorsal and ventral CA1 hippocampal synapses

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