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 invivo challenge to fluid homeostasis, induces LTD at glutamate synapses onto hypothalamic magnocellular neurosecretory cells (MNCs). LTD requires the activation of postsynaptic 2-adrenoceptors and the production of endocannabinoids that act ina 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 followinga successful response to an acute physiological challenge.From press release:In an article published in the June 25th edition of the journal Neuron, researchers at the Hotchkiss Brain Institute, University of Calgary, have found that synaptic plasticity, long implicated as a device for 'change' in the brain, may also be essential for stability.Homeostasis, the body's own mechanism of regulating and maintaining internal balance in the body, is necessary for survival. Precisely how the brain pulls off this tricky balancing act has not been well appreciated.By examining neural circuits that regulate fluid volume, Jaideep Bains, PhD, and colleagues, Brent Kuzmiski, PhD, and Quentin Pittman, PhD, have demonstrated that multiple forms of synaptic plasticity work to ensure that an effective response to a life-threatening challenge is followed by an immediate recovery of these neural circuits to pre-challenge conditions.These observations provide the first set of synaptic rules that help us understand how homeostatic setpoints are re-set in vivo. Based on their findings, Bains and colleagues, demonstrate that synaptic plasticity is essential for maintaining stability in a nervous system constantly bombarded by inputs from the outside world.This research was supported by the Canadian Institutes of Health Research (CIHR) and the Heart and Stroke Foundation of Alberta, Yukon and NWT. Bains is an AHFMR (Alberta Heritage Foundation for Medical Research) senior scholar while Pittman is an AHFMR medical scientist. Bains is an associate professor and Pittman a professor in the Department of Physiology and Biophysics. Both are members of the Hotchkiss Brain Institute in the Faculty of Medicine at the University of Calgary.
J. Brent Kuzmiski, Quentin J. Pittman, Jaideep S. Bains Metaplasticity of Hypothalamic Synapses following In Vivo Challenge Neuron 2009 June Hotchkiss Brain Institute and University of Calgary, Calgary, AB T2N 4N1, Canada.