Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long‐term depression in adult rat hippocampus

Abstract

1 During block of γ-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 (≈500 nM) during only the initial ≈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 (+)-α-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.