Altered long-term synaptic plasticity and kainate-induced Ca2+ transients in the substantia gelatinosa neurons in GLUK6-deficient mice

Functional kainate receptors are expressed in the spinal cord substantia gelatinosa region, and their activation contributes to bi-directional regulation of excitatory synaptic transmission at primary afferent synapses with spinal cord substantia gelatinosa neurons. However, no study has reported a role(s) for kainate receptor subtypes in long-term synaptic plasticity phenomena in this region. Using gene-targeted mice lacking glutamate receptor 5 (GLUK5) or GLUK6 subunit, we here show that GLUK6 subunit, but not GLUK5 subunit, is involved in the induction of long-term potentiation of excitatory postsynaptic potentials, evoked by two different protocols: (1) high-frequency primary afferent stimulation (100 Hz, 3 s) and (2) low-frequency spike-timing stimulation (1 Hz, 200 pulses). In addition, GLUK6 subunit plays an important role in the expression of kainate-induced Ca2+ transients in the substantia gelatinosa. On the other hand, genetic deletion of GLUK5 or GLUK6 subunit does not prevent the induction of long-term depression. These results indicate that unique expression of kainate receptors subunits is important in regulating spinal synaptic plasticity and thereby processing of sensory information, including pain.