Abstract
Neural networks that regulate an organism's internal environment must sense perturbations, respond appropriately, and then reset. These adaptations should be reflected as changes in the efficacy of the synapses that drive the final output of these homeostatic networks. Here we show that hemorrhage, an in vivo challenge to fluid homeostasis, induces LTD at glutamate synapses onto hypothalamic magnocellular neurosecretory cells (MNCs). LTD requires the activation of postsynaptic alpha2-adrenoceptors and the production of endocannabinoids that act in a retrograde fashion to inhibit glutamate release. In addition, both hemorrhage and noradrenaline downregulate presynaptic group III mGluRs. This loss of mGluR function allows high-frequency activity to potentiate these synapses from their depressed state. These findings demonstrate that noradrenaline controls a form of metaplasticity that may underlie the resetting of homeostatic networks following a successful response to an acute physiological challenge.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-Agonists / pharmacology
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Animals, Newborn
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Biophysics
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Carbolines / pharmacology
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Clonidine / pharmacology
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Down-Regulation / drug effects
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Drug Interactions
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation
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Excitatory Amino Acid Agents / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Glutamic Acid / metabolism
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Guanosine Diphosphate / analogs & derivatives
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Guanosine Diphosphate / pharmacology
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Hypothalamus / cytology*
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In Vitro Techniques
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Intracranial Hemorrhages / physiopathology*
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology*
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Male
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Microinjections / methods
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Neurons / physiology*
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Patch-Clamp Techniques / methods
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism
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Synapses / physiology*
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Thionucleotides / pharmacology
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Yohimbine / pharmacology
Substances
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Carbolines
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Excitatory Amino Acid Agents
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Piperidines
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Pyrazoles
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Receptor, Cannabinoid, CB1
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Receptors, Metabotropic Glutamate
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Thionucleotides
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metabotropic glutamate receptor 3
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Guanosine Diphosphate
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Yohimbine
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AM 251
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Glutamic Acid
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Egtazic Acid
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tryptoline
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guanosine 5'-O-(2-thiodiphosphate)
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Clonidine