Intrinsic burst-firing in lamina I spinoparabrachial neurons during adolescence

A subset of glutamatergic interneurons in the neonatal spinal superficial dorsal horn (SDH) exhibits intrinsic burst-firing (i.e. 'pacemaker' activity), which is tightly regulated by persistent, voltage-gated Na+ channels and classic inward-rectifying K+ (K(ir)2) channels and downregulated over the course of postnatal development. Ascending lamina I projection neurons targeting the parabrachial nucleus (PB) or periaqueductal gray (PAG) can also display pacemaker activity during early life. However, the degree to which the ionic mechanisms driving pacemaker activity are conserved across different cell types in the spinal dorsal horn, as well as whether the intrinsic bursting is restricted to newborn projection neurons, remains to be elucidated. Using in vitro patch clamp recordings from identified lamina I spinoparabrachial neurons in rat spinal cord slices, here we demonstrate that adolescent projection neurons retain their ability to generate pacemaker activity. In contrast to previous findings in lamina I interneurons, pacemaker projection neurons possessed higher membrane capacitance, lower membrane resistance, and a greater K-ir-mediated conductance compared to adjacent spinoparabrachial neurons that lacked intrinsic burst-firing. Nonetheless, as previously seen in interneurons, the bath application of riluzole to block persistent Na+ channels significantly dampened pacemaker activity in projection neurons. Collectively, these results suggest that intrinsic burst-firing in the developing dorsal horn can be generated by multiple combinations of ionic conductances, and highlight the need for further investigation into the mechanisms governing pacemaker activity within the major output neurons of the SDH network.

Automated summary

In a subset of glutamatergic interneurons in the neonatal spinal superficial dorsal horn (SDH), there is intrinsic burst-firing activity regulated by persistent Na+ channels and inward-rectifying K+ channels, which decreases during postnatal development. While ascending lamina I projection neurons targeting the parabrachial nucleus (PB) or periaqueductal gray (PAG) can also display pacemaker activity in early life, the mechanisms driving this activity and its conservation across cell types in the spinal dorsal horn remain unclear. Our study demonstrates that adolescent projection neurons retain the ability to generate pacemaker activity, with differences in membrane properties compared to adjacent neurons lacking intrinsic burst-firing. Further research is needed to understand the mechanisms governing pacemaker activity in the major output neurons of the SDH network.