Metabotropic glutamate receptor 1 activity generates persistent, N-methyl-D-aspartate receptor-dependent depression of hippocampal pyramidal cell excitability

摘要: Metabotropic glutamate receptors (mGluRs) are involved in many forms of neuronal plasticity. In the hippocampus, they have well-defined roles long-lasting both synaptic and intrinsic Here, we describe a novel form plasticity that call (S)-3,5-dihydroxyphenylglycine (DHPG)-mediated long-term depression excitability (DHPG-LDE), which is generated following transient pharmacological activation group I mGluRs. extracellular recordings from hippocampal slices, DHPG-LDE was expressed as antidromic compound action potentials (cAPs) CA1 or CA3 cells 4-min exposure to mGluR agonist (S)-DHPG. A similar phenomenon also seen for orthodromic fibre volleys evoked axons. single-cell pyramids, manifest persistent failures potential generation. blocked by (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), an antagonist mGluR1, but not 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), mGluR5 inhibitor. Although insensitive antagonists alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate/kainate gamma-aminobutyric acid(A) receptors, N-methyl-D-aspartate (NMDA) receptors. Similarly, recordings, DHPG-mediated spike were eliminated NMDA receptor antagonism. Long after (S)-DHPG washout, reversed mGluR1 application produced receptor-dependent depolarization pyramidal cells. This solely responsible DHPG-LDE, because level elicited raising K(+) increased amplitude cAP. did involve HCN channels protein synthesis, blockers kinase C tyrosine phosphatases.