Neuron (Cambridge, Mass.), 2012-06, Vol.74 (5), p.801-808
2012
Details
- Autor(en) / Beteiligte
- Titel
- Estradiol Acutely Suppresses Inhibition in the Hippocampus through a Sex-Specific Endocannabinoid and mGluR-Dependent Mechanism
- Ist Teil von
- Neuron (Cambridge, Mass.), 2012-06, Vol.74 (5), p.801-808
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- The steroid 17β-estradiol (E2) is well known to influence hippocampal functions such as memory, affective behaviors, and epilepsy. There is growing awareness that in addition to responding to ovarian E2, the hippocampus of both males and females synthesizes E2 as a neurosteroid that could acutely modulate synaptic function. Previous work on acute E2 actions in the hippocampus has focused on excitatory synapses. Here, we show that E2 rapidly suppresses inhibitory synaptic transmission in hippocampal CA1. E2 acts through the α form of the estrogen receptor to stimulate postsynaptic mGluR1-dependent mobilization of the endocannabinoid anandamide, which retrogradely suppresses GABA release from CB1 receptor-containing inhibitory presynaptic boutons. Remarkably, this effect of E2 is sex specific, occurring in females but not in males. Acute E2 modulation of endocannabinoid tone and consequent suppression of inhibition provide a mechanism by which neurosteroid E2 could modulate hippocampus-dependent behaviors in a sex-specific manner. ► Estradiol acutely suppresses GABA release at a subset of inputs to CA1 cells ► Estradiol acts by mobilizing anandamide to retrogradely activate CB1Rs ► Acute estradiol-induced suppression of inhibition is ERα and mGluR1 dependent ► Acute estradiol-induced suppression of inhibition is sex specific Sex differences in the brain extend beyond reproductive function. Huang and Woolley describe a sex-specific mechanism of synaptic modulation in the hippocampus by which estradiol acutely suppresses GABAergic inhibition through regulation of endocannabinoids in females but not in males.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2012.03.035Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3372866
- Format
- –
- Schlagworte
- Anandamide, Animals, Behavior, Benzodioxoles - pharmacology, Benzoxazines - pharmacology, Biophysics, Brain, CA1 Region, Hippocampal - cytology, Cannabinoid CB1 receptors, Cannabinoid Receptor Modulators - agonists, Cannabinoid Receptor Modulators - antagonists & inhibitors, Cannabinoid Receptor Modulators - metabolism, Castration, Dose-Response Relationship, Drug, Drug Interactions, Electric Stimulation, Emotional behavior, Endocannabinoids, Enzyme Inhibitors - pharmacology, Epilepsy, Estradiol, Estradiol - pharmacology, Estrogen receptors, Estrogens - pharmacology, Excitatory Amino Acid Agents - pharmacology, Female, Females, GABA Antagonists - pharmacology, gamma -Aminobutyric acid, Gender differences, Hippocampus, In Vitro Techniques, Inhibitory Postsynaptic Potentials - drug effects, Lactones - pharmacology, Male, Males, Memory, Morpholines - pharmacology, NAD - pharmacology, Naphthalenes - pharmacology, Neural Inhibition - drug effects, Neurons - drug effects, Neurons - physiology, Neurosteroids, Orlistat, Patch-Clamp Techniques, Phenols, Piperidines - pharmacology, Presynapse, Pyrazoles - pharmacology, Pyridazines - pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate - metabolism, Rodents, Sex, Steroid hormones, Studies, Synapses, Synaptic transmission