Substance P induces the reversible formation of varicosities in the dendrites of rat brainstem neurons

Abstract

This study investigated the ability of substance P (Sub P) to induce dendritic varicosities (DVs) or beads in neurons of the rostral ventromedial medulla (RVM) of the rat. Microinjection of 5–200pmol Sub P in the RVM produced a concentration-dependent increase in the number of DVs in distal dendrites of RVM neurons that were immunoreactive for the neurokinin-1 receptor, but not serotonin. The effect was reversible, as DVs were essentially absent 2 and 4h after microinjection. Fluoro-Jade B labeled neurons were not evident in the RVM 4days after microinjection of Sub P, although such neurons were present 4days after microinjection of a neurotoxic dose of kainate. Bath application of Sub P to brainstem slices for a period as brief as 30s also produced DVs in neurokinin-1 immunoreactive RVM neurons. Prior exposure to L-703606 prevented the formation of DVs by Sub P, implicating the neurokinin-1 receptor, a Gq type of G protein coupled receptor, in the formation of DVs by Sub P. Finally, stabilization of microtubules by prior exposure to taxol also prevented the formation of DVs, consistent with the idea that increases in intracellular Ca2+ lead to the formation of DVs secondary to a disruption of the linear arrays of microtubules in dendrites. These data establish a mechanistic basis for the formation of DVs by Sub P and support further studies to test the hypothesis that the formation of DVs is a morphological mechanism by which neurons can regulate their responses to inhibitory or excitatory inputs.