Hemorrhage induced inactivation of presynaptic group III mGluRs controls metaplasticity in circuits regulating fluid balance

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In response to perturbations in body fluid homeostasis, noradrenaline (NA) is released in the paraventricular nucleus (PVN) of the hypothalamus to modulate neuroendocrine output. Here, we use whole‐cell patch clamp recordings from magnocellular neurosecretory cells in the PVN to show that bath application of NA (5 min, 100 μM) induces a robust, fast‐acting, long‐term depression (LTD) at glutamatergic synapses. This LTD is accompanied by a loss of presynaptic signaling at group III mGluRs. Depressed, but not naïve glutamatergic synapses exhibit a rapid presynaptic potentiation in response to high frequency stimulation. To determine if a physiological stressor that activates noradrenergic fibers to the PVN could induce similar changes in synaptic strength, slices were taken from rats that were hemorrhaged (under anesthesia, removal of 25% blood volume via cardiac puncture). In hemorrhaged rats, glutamatergic synapses displayed a reduced release probability and were unresponsive to the mGluR agonist, L‐AP4. High frequency stimulation of these synapses induced a rapid LTP. The ability of synapses to switch between depressed and potentiated states may be an important mechanism for filtering irrelevant activity (i.e. emotional inputs) from activity critical to controlling cardiovascular homeostasis. This work was supported by the Canadian Institutes of Health Research.