Induction of homosynaptic long-term depression at spinal synapses of sensory a delta-fibers requires activation of metabotropic glutamate receptors.

The synaptic strength between primary afferent Adelta-fibers, many of which convey pain-related information, and second order neurons in the spinal dorsal horn can be depressed for prolonged periods of time in a use- and N-methyl-D-aspartate receptor-dependent fashion. Here, we have used a transverse spinal cord slice-dorsal root preparation of young rat to characterize the nature of this form of long-term depression and the role of metabotropic glutamate receptors. Dorsal roots were bisected and intracellular recordings were made from lamina II neurons with independent excitatory synaptic inputs from both dorsal root halves. Conditioning stimulation of one dorsal root half (1 Hz, 900 pulses) induced long-term depression that was specific for the stimulated pathway, i. e. homosynaptic in nature. The induction of long-term depression was prevented by non-selective group I and group II mGluR antagonist (S)-alpha-methyl-4-carboxyphenylglycine, by selective group I receptor antagonist (S)-4-carboxyphenylglycine and by selective group II mGluR antagonist (RS)-alpha-methylserine-O-phosphate monophenyl ester. Group III mGluR antagonist (RS)-alpha-methylserine-O-phosphate was ineffective. Short-term depression was not affected by any of these antagonists.Thus, a homosynaptic form of long-term depression exists at putative nociceptive synapses in the spinal dorsal horn and its induction requires the activation of both group I and II metabotropic glutamate receptors.