Mechanisms and Cell Type-Dependence of Non-Hebbian Long-Term Potentiation at Primary Afferent Synapses in the Mouse Spinal Superficial Dorsal Horn

Abstract

Sensory synapses onto ascending spinal projection neurons in the superficial dorsal horn (SDH) can exhibit non-Hebbian plasticity, such as when the firing of primary afferent neurons alone is sufficient to induce long-term potentiation (LTP), following neonatal tissue damage or D1/D5 dopamine receptor activation. However, whether non-Hebbian LTP can be induced at sensory synapses in the absence of tissue injury or exogenous neuromodulatory signaling, the molecular mechanisms underlying this form of synaptic plasticity, and the degree to which non-Hebbian LTP occurs in a cell type-dependent manner within the SDH remain unclear. Here, non-Hebbian plasticity at primary afferent synapses onto lamina I spinoparabrachial neurons, GABAergic (VGAT+) interneurons, and putative glutamatergic (VGAT−) interneurons was examined using ex vivo patch-clamp recordings from the adult mouse SDH of both sexes. Prolonged low-frequency activation of primary afferent inputs evoked non-Hebbian LTP in ascending projection neurons, which reflected an increased probability of presynaptic glutamate release. While the non-Hebbian LTP occurred independently of postsynaptic depolarization, postsynaptic Ca 2+ influx downstream of NMDAR and mGluR5 activation was required for LTP generation. Importantly, both the prevalence and magnitude of non-Hebbian LTP were significantly greater in lamina I spinoparabrachial neurons compared with either GABAergic or glutamatergic interneurons in the mature SDH. Overall, these results suggest that the major output neurons of the SDH network can preferentially amplify ongoing nociceptive input via non-Hebbian mechanisms in the absence of a pathological state.