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Metabotropic glutamate receptor 1 activity generates persistent, N ‐methyl‐ d ‐aspartate receptor‐dependent depression of hippocampal pyramidal cell excitability
Author(s) -
Clement J. P.,
Randall A. D.,
Brown J. T.
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06780.x
Subject(s) - kainate receptor , metabotropic glutamate receptor , chemistry , neuroscience , nmda receptor , metabotropic receptor , long term depression , metabotropic glutamate receptor 1 , glutamate receptor , pharmacology , receptor , biology , ampa receptor , biochemistry
Metabotropic glutamate receptors (mGluRs) are involved in many forms of neuronal plasticity. In the hippocampus, they have well‐defined roles in long‐lasting forms of both synaptic and intrinsic plasticity. Here, we describe a novel form of long‐lasting intrinsic plasticity that we call ( S )‐3,5‐dihydroxyphenylglycine (DHPG)‐mediated long‐term depression of excitability (DHPG‐LDE), and which is generated following transient pharmacological activation of group I mGluRs. In extracellular recordings from hippocampal slices, DHPG‐LDE was expressed as a long‐lasting depression of antidromic compound action potentials (cAPs) in CA1 or CA3 cells following a 4‐min exposure to the group I mGluR agonist ( S )‐DHPG. A similar phenomenon was also seen for orthodromic fibre volleys evoked in CA3 axons. In single‐cell recordings from CA1 pyramids, DHPG‐LDE was manifest as persistent failures in antidromic action potential generation. DHPG‐LDE was blocked by ( S )‐(+)‐ a ‐amino‐4‐carboxy‐2‐methylbenzeneacetic acid (LY367385), an antagonist of mGluR1, but not 2‐methyl‐6‐(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 inhibitor. Although insensitive to antagonists of α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate/kainate and γ‐aminobutyric acid A receptors, DHPG‐LDE was blocked by antagonists of N ‐methyl‐ d ‐aspartate (NMDA) receptors. Similarly, in single‐cell recordings, DHPG‐mediated antidromic spike failures were eliminated by NMDA receptor antagonism. Long after ( S )‐DHPG washout, DHPG‐LDE was reversed by mGluR1 antagonism. A 4‐min application of ( S )‐DHPG also produced an NMDA receptor‐dependent persistent depolarization of CA1 pyramidal cells. This depolarization was not solely responsible for DHPG‐LDE, because a similar level of depolarization elicited by raising extracellular K + increased the amplitude of the cAP. DHPG‐LDE did not involve HCN channels or protein synthesis, but was eliminated by blockers of protein kinase C or tyrosine phosphatases.