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

Satoru Otani and John A. Connor ¹

1. During block of -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 (+)--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.

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