Cell type-dependent short-term plasticity and dopaminergic modulation of sensory synapses onto mouse superficial dorsal horn neurons.

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 to 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.Significance Statement Short-term plasticity (STP) serves as a temporal filter to preferentially transmit low- or high-frequency inputs across CNS synapses. Here we demonstrate that STP occurs in a cell type-dependent manner at sensory synapses onto mouse superficial dorsal horn (SDH) neurons. During repetitive stimulation, putative unmyelinated nociceptors exhibit stronger short-term depression (STD) at their synapses onto GABAergic interneurons compared to other SDH neurons, which could transiently compromise the function of the spinal inhibitory 'gate' controlling ascending nociceptive signaling to the brain. While dopamine failed to alter STD at sensory synapses in the adult SDH, it selectively reduced primary afferent-evoked drive onto spinoparabrachial neurons and excitatory interneurons, which may contribute to the previously documented anti-nociceptive effects of dopamine released into the spinal cord.