scholarly journals Estrus-Cycle Regulation of Cortical Inhibition

2018 ◽  
Author(s):  
Ann M. Clemens ◽  
Constanze Lenschow ◽  
Prateep Beed ◽  
Lanxiang Li ◽  
Rosanna Sammons ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Β ◽  
Cortical Inhibition ◽  
Female Rats ◽  
Estrus Cycle ◽  
Whole Cell ◽  
Fast Spiking ◽  
Whole Cell Recordings

SummaryFemale mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performedin vivojuxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change.In vivowhole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus.In situhybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings.In vivoandin vitroexperiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen receptor β mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female brain.

scholarly journals Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

2010 ◽  
Vol 17 (3) ◽  
pp. 731-742 ◽  
Author(s):  
Donatella Dondi ◽  
Margherita Piccolella ◽  
Andrea Biserni ◽  
Sara Della Torre ◽  
Balaji Ramachandran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Cultured Cells ◽  
Estrogen Receptor Β ◽  
Continuous Administration ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Androgen Ablation Therapy

Prostate cancer (PC) develops in response to an abnormal activation of androgen receptor induced by circulating androgens and, in its initial stages, is pharmacologically controlled by androgen blockade. However, androgen ablation therapy often allows androgen-independent PC development, generally characterized by increased invasiveness. We previously reported that 5α-androstane-3β,17β-diol (3β-Adiol) inhibits the migration of PC cell lines via the estrogen receptor β (ERβ) activation. Here, by combining in vitro assays and in vivo imaging approaches, we analyzed the effects of 3β-Adiol on PC proliferation, migration, invasiveness, and metastasis in cultured cells and in xenografts using luciferase-labeled PC3 (PC3-Luc) cells. We found that 3β-Adiol not only inhibits PC3-Luc cell migratory properties, but also induces a broader anti-tumor phenotype by decreasing the proliferation rate, increasing cell adhesion, and reducing invasive capabilities in vitro. All these 3β-Adiol activities are mediated by ERβ and cannot be reproduced by the physiological estrogen, 17β-estradiol, suggesting the existence of different pathways activated by the two ERβ ligands in PC3-Luc cells. In vivo, continuous administration of 3β-Adiol reduces growth of established tumors and counteracts metastasis formation when PC3-Luc cells are engrafted s.c. in nude mice or are orthotopically injected into the prostate. Since 3β-Adiol has no androgenic activity, and cannot be converted to androgenic compounds, the effects here described entail a novel potential application of this agent against human PC.

Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity

2006 ◽  
Vol 290 (1) ◽  
pp. H295-H303 ◽  
Author(s):  
Rajesh G. Mishra ◽  
Frank Z. Stanczyk ◽  
Kenneth A. Burry ◽  
Suzanne Oparil ◽  
Benita S. Katzenellenbogen ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Binding Activity ◽  
Estrogen Receptor Β ◽  
Vascular Muscle ◽  
Vasoconstrictor Response ◽  
Endogenous Estrogen ◽  
17Β Estradiol ◽  
In Vitro Treatment

Previous reports showed that 17β-estradiol implants attenuate in vivo coronary hyperreactivity (CH), characterized by long-duration vasoconstrictions (in coronary angiographic experiments), in menopausal rhesus monkeys. Prolonged Ca2+ contraction signals that correspond with CH in coronary vascular muscle cells (VMC) to the same dual-constrictor stimulus, serotonin + the thromboxane analog U-46619, in estrogen-deprived VMC were suppressed by >72 h in 17β-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-β (ER-β) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E3 treatment in vivo for 4 wk significantly attenuated the angiographically evaluated vasoconstrictor response to intracoronary serotonin + U-46619 challenge. In vitro treatment of rhesus coronary VMC for >72 h with nanomolar E3 attenuated late Ca2+ signals. This reduction of late Ca2+ signals also appeared after >72 h of treatment with subnanomolar 5α-androstane-3β,17β-diol (3β-Adiol), an endogenous dihydrotestosterone metabolite with ER-β binding activity. R,R-tetrahydrochrysene, a selective ER-β antagonist, significantly blocked the E3- and 3β-Adiol-mediated attenuation of late Ca2+ signal increases. ER-β and thromboxane-prostanoid receptor (TPR) were coexpressed in coronary arteries and aorta. In vivo E3 treatment attenuated aortic TPR expression. Furthermore, in vitro treatment with E3 or 3β-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E3- and 3β-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-β-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.

scholarly journals Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico

2012 ◽  
Vol 107 (5) ◽  
pp. 1476-1488 ◽  
Author(s):  
Max L. Schiff ◽  
Alex D. Reyes
Keyword(s):  
Auditory Cortex ◽  
Pyramidal Neurons ◽  
Modulation Frequency ◽  
Primary Auditory Cortex ◽  
Cortical Inhibition ◽  
Membrane Properties ◽  
Thalamic Stimulation ◽  
Fast Spiking

We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning.

scholarly journals A bi-faceted role of estrogen receptor β in breast cancer

2013 ◽  
Vol 20 (3) ◽  
pp. R127-R139 ◽  
Author(s):  
Etienne Leygue ◽  
Leigh C Murphy
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Large Body ◽  
Estrogen Receptor Β ◽  
Cancer Tissue ◽  
Culture Studies ◽  
Growth And Survival

Despite over 15 years of research, the exact role, if any, played by estrogen receptor β (ERβ) in human breast cancer remains elusive. A large body of data bothin vitroandin vivosupports its role as an antiproliferative, pro-apoptotic factor especially when co-expressed with ERα. However, there is a smaller body of data associating ERβ with growth and survival in breast cancer. In clinical studies and most often in cell culture studies, the pro-growth and pro-survival activity of ERβ occurs in ERα-negative breast cancer tissue and cells. This bi-faceted role of ERβ is discussed in this review.

scholarly journals Multiple two-photon targeted whole-cell patch-clamp recordings from monosynaptically connected neurons in vivo

2019 ◽  
Author(s):  
Jean-Sébastien Jouhanneau ◽  
James F.A. Poulet
Keyword(s):  
Patch Clamp ◽  
Whole Cell ◽  
Two Photon ◽  
Cell Patch Clamp ◽  
Whole Cell Patch Clamp ◽  
Brain States ◽  
Post Hoc ◽  
Whole Cell Recordings

AbstractAlthough we know a great deal about monosynaptic connectivity, transmission and integration in the mammalian nervous system from in vitro studies, very little is known in vivo. This is partly because it is technically difficult to evoke action potentials and simultaneously record small amplitude subthreshold responses in closely (< 150 µm) located pairs of neurons. To address this, we have developed in vivo two-photon targeted multiple (2 – 4) whole-cell patch clamp recordings of nearby neurons in superficial cortical layers 1 to 3. Here we describe a step-by-step guide to this approach in the anesthetised mouse primary somatosensory cortex, including: the design of the setup, surgery, preparation of pipettes, targeting and acquisition of multiple whole-cell recordings, as well as in vivo and post-hoc histology. The procedure takes ∼ 4 hours from start of surgery to end of recording and allows examinations both into the electrophysiological features of unitary excitatory and inhibitory monosynaptic inputs during different brain states as well as the synaptic mechanisms of correlated neuronal activity.

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