Mechanisms and cell type-dependence of non-Hebbian long-term potentiation at primary afferent synapses in the mouse spinal superficial dorsal horn.

While non-Hebbian long-term potentiation (LTP) at primary afferent synapses onto projection neurons in the spinal superficial dorsal horn (SDH) is enabled following neonatal tissue damage or exogenous D1/D5 dopamine receptor signaling, whether non-Hebbian LTP occurs under normal conditions and is restricted to sensory synapses onto projection neurons within the SDH network remains unknown. Here we demonstrate that prolonged low-frequency stimulation of primary afferents evokes non-Hebbian LTP in ∼90% of lamina I spinoparabrachial neurons by enhancing presynaptic function, while such LTP is rarely seen at sensory synapses onto inhibitory interneurons. This cell type-dependent synaptic plasticity could increase the gain of ascending nociceptive transmission to the brain following the persistent activation of sensory inputs to the SDH and thereby enhance pain sensitivity.