Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus.
1. During block of gamma-aminobutyric acid-A-mediated inhibition, low-frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral-CA1 neuron synapses of adult rat hippocampus induced an N-methyl-D-aspartate receptor-independent, postsynaptic Ca2+-dependent depression of synaptic strength (long-term depression; LTD). 2. Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (approximately 500 nM) during only the initial approximately 30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. 3. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. 4. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. 5. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). 6. These results suggest that LTD induction in adult hippocampus by prolonged low-frequency stimulation depends on both a rapid Ca2+ influx through voltage-sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C.
Laboratoire de Neurobiologie et Neuropharmacologie du Developpement, Institut des Neurosciences, Universite de Paris VI, 7 Quai Saint Bernard, Paris 75005, France. satoru.otani@snv.jussieu.fr
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry / Q000201:enzymology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D002118:Calcium; D002614:Chelating Agents; D004533:Egtazic Acid; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D016257:Fura-2; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D011493:Protein Kinase C; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid