Axon diversity of lamina I local‐circuit neurons in the lumbar spinal cord

Abstract

Spinal lamina I is a key area for relaying and integrating information from nociceptive primary afferents with various other sources of inputs. Although lamina I projection neurons have been intensively studied, much less attention has been given to local-circuit neurons (LCNs), which form the majority of the lamina I neuronal population. In this work the infrared light-emitting diode oblique illumination technique was used to visualize and label LCNs, allowing reconstruction and analysis of their dendritic and extensive axonal trees. We show that the majority of lamina I neurons with locally branching axons fall into the multipolar (with ventrally protruding dendrites) and flattened (dendrites limited to lamina I) somatodendritic categories. Analysis of their axons revealed that the initial myelinated part gives rise to several unmyelinated small-diameter branches that have a high number of densely packed, large varicosities and an extensive rostrocaudal (two or three segments), mediolateral, and dorsoventral (reaching laminae III–IV) distribution. The extent of the axon and the occasional presence of long, solitary branches suggest that LCNs may also form short and long propriospinal connections. We also found that the distribution of axon varicosities and terminal field locations show substantial heterogeneity and that a substantial portion of LCNs is inhibitory. Our observations indicate that LCNs of lamina I form intersegmental as well as interlaminar connections and may govern large numbers of neurons, providing anatomical substrate for rostrocaudal “processing units” in the dorsal horn. J. Comp. Neurol. 521:2719–2741, 2013.

Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs

“…Similarly to our earlier observations Szucs et al, 2013) dendritic origin of the axon was also frequent among neurons outside lamina I and in the LSN.…”

“…We compared basic morphometric parameters of these neurons with a pooled sample of 3-D reconstructed PNs and LCNs (n=4 for each, L-I in Fig. 3) from our earlier works Szucs et al, 2013). Neurons lateral to lamina I and in the LSN had more stem dendrites ( Fig.…”

“…16 out of 32 successfully recovered neurons (cells 1-7, 10-14, 18, 23, 29 and 31) could be classified based on the presence or absence of a single projecting axon as projection or local-circuit neurons (detailed criteria described in our previous works: Szucs et al, 2010 andSzucs et al, 2013). Regular PNs gave rise to a single projection axon that originated from the cell body or one of the primary dendrites, crossed the midline in the anterior commissure and ascended in the contralateral anterolateral column (c-ALT).…”

“…5G and text in Szucs et al, 2013) axon branch that entered and ascended in the i-DF or i-DLF. Another characteristic morphological feature was the presence of single thin ipsilateral axon collaterals that had numerous varicosities and descended in the DLF or Lissauer´s tract (Table 1).…”

“…Although the composition of the intrinsic longitudinal unmyelinated axon system in the lateral aspect of the superficial dorsal horn is not fully described it undoubtedly contains ipsilateral collaterals of PNs in lamina I and a large number of thin axons that belong to lamina I local-circuit neurons (LCNs; Szucs et al, 2013 Gwyn and Waldron (1968;1969) who first described the structure. LSN neurons can be activated by noxious stimulation (Olave and Maxwell, 2004), receiving afferent input from C-fibers innervating muscles (Olave and Maxwell, 2004) and viscera (Sugiura et al, 1989) and project through ascending tracts to the brainstem, hypothalamus, and thalamus (Menetrey et al, 1982;Pechura and Liu, 1986;Menetrey and Basbaum, 1987;Leah et al, 1988;Burstein et al,1990).…”