title: Endogenous hippocampal LTD that is enabled by spatial object recognition requires activation of NMDA receptors and the metabotropic glutamate receptor, mGlu5.
abstract: Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent plasticity to afferent stimulation when coupled with a spatial learning event, whereby the afferent stimulation normally produces short-term plasticity or no change in synaptic strength if given in the absence of novel learning. Recently, it was reported that in the mouse hippocampus intrinsic long-term depression (LTD > 24 h) occurs when test-pulse afferent stimulation is coupled with a novel spatial learning. It is not known to what extent this phenomenon shares molecular properties with synaptic plasticity that is typically induced by means of patterned electrical afferent stimulation. In previous work, we showed that a novel spatial object recognition task facilitates LTD at the Schaffer collateral-CA1 synapse of freely behaving adult mice, whereas reexposure to the familiar spatial configuration ∼24 h later elicited no such facilitation. Here we report that treatment with the NMDA receptor antagonist, (±)-3-(2-Carboxypiperazin-4-yl)-propanephosphonic acid (CPP), or antagonism of metabotropic glutamate (mGlu) receptor, mGlu5, using 2-methyl-6-(phenylethynyl) pyridine (MPEP), completely prevented LTD under the novel learning conditions. Behavioral assessment during re-exposure after application of the antagonists revealed that the animals did not remember the object during novel exposure and treated them as if they were novel. Under these circumstances, where the acquisition of novel spatial information was involved, LTD was facilitated. Our data support that the endogenous LTD that is enabled through novel spatial learning in adult mice is critically dependent on the activation of both the NMDA receptors and mGlu5.
authors.affiliation: Department of Neurophysiology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Jinzhong Jeremy
authors.initials: JJ
authors.lastname: Goh
authors.forename: Denise
authors.initials: D
authors.lastname: Manahan-Vaughan
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology*
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate