PMID- 19555652 OWN - NLM STAT- MEDLINE DCOM- 20090709 LR - 20220309 IS - 1097-4199 (Electronic) IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 62 IP - 6 DP - 2009 Jun 25 TI - Metaplasticity of hypothalamic synapses following in vivo challenge. PG - 839-49 LID - 10.1016/j.neuron.2009.05.027 [doi] AB - 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. FAU - Kuzmiski, J Brent AU - Kuzmiski JB AD - Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada. FAU - Pittman, Quentin J AU - Pittman QJ FAU - Bains, Jaideep S AU - Bains JS LA - eng GR - 15116/CAPMC/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (Adrenergic alpha-Agonists) RN - 0 (Adrenergic alpha-Antagonists) RN - 0 (Carbolines) RN - 0 (Excitatory Amino Acid Agents) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (Receptors, Metabotropic Glutamate) RN - 0 (Thionucleotides) RN - 0 (metabotropic glutamate receptor 3) RN - 146-91-8 (Guanosine Diphosphate) RN - 2Y49VWD90Q (Yohimbine) RN - 3I4FA44MAI (AM 251) RN - 3KX376GY7L (Glutamic Acid) RN - 526U7A2651 (Egtazic Acid) RN - 65027TMI0H (tryptoline) RN - 71376-97-1 (guanosine 5'-O-(2-thiodiphosphate)) RN - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) RN - MN3L5RMN02 (Clonidine) SB - IM MH - Adrenergic alpha-Agonists/pharmacology MH - Adrenergic alpha-Antagonists/pharmacology MH - Animals MH - Animals, Newborn MH - Biophysics MH - Carbolines/pharmacology MH - Clonidine/pharmacology MH - Down-Regulation/drug effects MH - Drug Interactions MH - Egtazic Acid/analogs & derivatives/pharmacology MH - Electric Stimulation MH - Excitatory Amino Acid Agents/pharmacology MH - Excitatory Postsynaptic Potentials/drug effects/physiology MH - Glutamic Acid/metabolism MH - Guanosine Diphosphate/analogs & derivatives/pharmacology MH - Hypothalamus/*cytology MH - In Vitro Techniques MH - Intracranial Hemorrhages/*physiopathology MH - Long-Term Synaptic Depression/drug effects/*physiology MH - Male MH - Microinjections/methods MH - Neurons/*physiology MH - Patch-Clamp Techniques/methods MH - Piperidines/pharmacology MH - Pyrazoles/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Cannabinoid, CB1/antagonists & inhibitors MH - Receptors, Metabotropic Glutamate/metabolism MH - Synapses/*physiology MH - Thionucleotides/pharmacology MH - Yohimbine/pharmacology PMC - PMC3560287 MID - CAMS2607 OID - NLM: CAMS2607 EDAT- 2009/06/27 09:00 MHDA- 2009/07/10 09:00 PMCR- 2013/01/31 CRDT- 2009/06/27 09:00 PHST- 2008/10/01 00:00 [received] PHST- 2009/02/17 00:00 [revised] PHST- 2009/05/20 00:00 [accepted] PHST- 2009/06/27 09:00 [entrez] PHST- 2009/06/27 09:00 [pubmed] PHST- 2009/07/10 09:00 [medline] PHST- 2013/01/31 00:00 [pmc-release] AID - S0896-6273(09)00430-9 [pii] AID - 10.1016/j.neuron.2009.05.027 [doi] PST - ppublish SO - Neuron. 2009 Jun 25;62(6):839-49. doi: 10.1016/j.neuron.2009.05.027.