Inhibition of Acute mGluR5-Dependent Depression in Hippocampal CA1 by High-Frequency Magnetic Stimulation

Abstract

High-frequency magnetic stimulation (HFMS) applied directly to the hippocampal slice preparation in vitro induces activity-dependent synaptic plasticity and metaplasticity. In addition, changes in synaptic transmission following HFMS involve the activation of N-methyl-D-aspartate and metabotropic glutamate receptors (mGluR). Here, we asked whether a short period of HFMS (5 × 10 delta-burst trains, duration of ~1 min) could alter mGluR5-mediated depression at Schaffer collateral–CA1 synapses in the acute brain slice preparation at 30 min after HFMS. To this end, we obtained field excitatory postsynaptic potential (fEPSP) slopes from Schaffer collateral–CA1 synapses after HFMS or control. First, we demonstrated that activity-dependent plasticity following HFMS depends on the slice orientation towards the magnetic coil indicating specific ion fluxes induced by magnetic fields. Second, we found that the mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine reduced the field excitatory postsynaptic potential (fEPSP) slopes in control slices but rather enhanced them in HFMS-treated slices. In contrast, the compound (S)-3,5-dihydroxyphenylglycine acting at both mGluR1 and mGluR5 reduced fEPSP slopes in both control and HFMS-treated slices. Importantly, the mGluR-dependent effects were independent from the slice-to-coil orientation indicating that asynchronous glutamate release could play a role. We conclude that a short period of HFMS inhibits subsequently evoked mGluR5-dependent depression at Schaffer collateral–CA1 synapses. This could be relevant for repetitive transcranial magnetic stimulation in psychiatric disorders such as major depression.

Keywords

• CHPG
• DHPG
• NMDA
• group I mGluR
• adolescent rat
• gabazine