Cell Type-Dependent Short-Term Plasticity and Dopaminergic Modulation of Sensory Synapses onto Mouse Superficial...

While transient changes in synaptic strength occurring during the repetitive firing of primary afferent inputs to the spinal superficial dorsal horn (SDH) are predicted to strongly influence the fidelity with which nociceptive signals are transmitted through the SDH network, little is known about whether the properties of short-term plasticity (STP) at sensory synapses depend on the identity of the postsynaptic target or whether STP is under the control of neuromodulators such as dopamine. Here we investigate these issues using ex vivo patch-clamp recordings from identified lamina I spinoparabrachial neurons, inhibitory interneurons (VGAT+), and putative excitatory interneurons (VGAT-) in spinal cord slices from adult mice of both sexes. Repeated activation of A-fiber inputs to the SDH evoked short-term depression (STD) across all major subtypes of SDH neurons, although the magnitude of STD was greatest in projection neurons with high-frequency stimulation. Meanwhile, repetitive activation of C-fiber synapses onto GABAergic interneurons evoked more pronounced STD compared with excitatory neurons across a range of stimulation frequencies. Both A-fiber and C-fiber synapses recovered from STD at a similar rate across the different SDH cell types examined. Dopamine (20 µM) significantly depressed the overall glutamatergic drive, and reduced afferent-evoked firing, selectively in spinoparabrachial neurons and excitatory interneurons without changes in the properties of STP. Collectively, these findings reveal novel potential mechanisms by which the efficacy of the spinal inhibitory "gate," and thus the gain of ascending nociceptive transmission to the brain, may be rapidly altered during periods of strong sensory input to the SDH network.