Essential roles of mGluR1 and inhibitory synaptic transmission in NMDA-independent long-term potentiation in the spinal trigeminal interpolaris

Aims Patterns of synaptic activity determine synaptic strengthening or weakening that is typically represented as long-term potentiation (LTP) and long-term depression (LTD), respectively. In the present study, we aim to test whether a conditioning stimulation of the spinal trigeminal subnucleus caudalis (Vc) induces LTP at excitatory synapses in the subnucleus interpolaris (Vi) and to characterize the LTP. Main methods Generally, a presynaptic high-frequency stimulation (HFS) protocol can induce LTP at excitatory synapses in the brain, including the spinal cord. Therefore, LTP in the Vi was induced by the HFS (3 tetani at 100 Hz) of Vc in the horizontal brainstem slices. By pretreating slices with antagonists for NMDA receptors, metabotropic glutamate receptor subtype 1 or 5 (mGluR1 or 5), GABA_A receptors, glycine receptors and Ca^{2 +} chelator, the LTP was characterized. Key findings The HFS reliably but slowly induced LTP of excitatory synaptic transmission in the Vi. This LTP was not dependent on NMDA receptor activation; however, it did require the activation of mGluR1, but not mGluR5, and an intracellular Ca^{2 +} rise. Interestingly, this LTP induction required inhibitory synaptic transmission mediated by GABA_A and glycine receptors, and coincided with the slow development of LTD at GABAergic synapses. The GABAergic LTD was mediated by mGluR1 and the intracellular Ca^{2 +} rise. Significance These data suggest that the modulation of GABAergic synaptic transmission by conditioning synaptic activity contributes to the induction and expression of LTP at excitatory synapses in the Vi.