Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing

Abstract

Tan AM, Choi J-S, Waxman SG, Hains BC. Dendritic spine remodeling after spinal cord injury alters neuronal signal processing. J Neurophysiol 102: 2396 -2409, 2009. First published August 19, 2009 doi:10.1152/jn.00095.2009. Central sensitization, a prolonged hyperexcitability of dorsal horn nociceptive neurons, is a major contributor to abnormal pain processing after spinal cord injury (SCI). Dendritic spines are micron-sized dendrite protrusions that can regulate the efficacy of synaptic transmission. Here we used a computational approach to study whether changes in dendritic spine shape, density, and distribution can individually, or in combination, adversely modify the input-output function of a postsynaptic neuron to create a hyperexcitable neuronal state. The results demonstrate that a conversion from thin-shaped to more mature, mushroom-shaped spine structures results in enhanced synaptic transmission and fidelity, improved frequency-following ability, and reduced inhibitory gating effectiveness. Increasing the density and redistributing spines toward the soma results in a greater probability of action potential activation. Our results demonstrate that changes in dendritic spine morphology, documented in previous studies on spinal cord injury, contribute to the generation of pain following SCI.

Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury

“…The dendritic spine profiles we observed after SCI below the injury can have direct biophysical effects on motor neuron excitability Segev and Rall 1988;Tan et al 2009). The distribution of spine synapses closer to motor neuron cell bodies can increase the overall impact of excitatory input and transmission.…”

“…Our present findings demonstrate robust changes in dendritic spine morphology on ␣-motor neurons after SCI, including an increase in dendritic spine density, a distribution of spines closer to the cell body, and the presence of more mature dendritic spines. These postsynaptic dendritic changes have been shown to accompany increased neuronal excitability after SCI (Rall et al 1992;Segev and Rall 1998;Tan et al 2009). In agreement, we observed a significant loss of H-reflex RDD below the injury (i.e., increased H/M ratio), indicative of spasticity (Boulenguez et al 2010;Matthews 1966;Nielsen et al 2007).…”

“…These criteria for two spine geometric categories were used because classification into only two spine shapes allowed us to use simple but very strict rules in classifying spine morphology. Although this approach prevented the discrimination of subtle variations in spine shape, it allowed the collection of a very large sample size, and we and others have described the physiological characteristics of thin and mushroom spine shapes on neuronal and circuit function (Bourne and Harris 2007;Holmes 1990;Tan et al 2009). Note that these criteria do not imply the physiological characterization of the neurons we analyzed, but rather control for morphological diversity within the sampled spinal motor neuron population (Kitzman 2005;Tashiro and Yuste 2003).…”

“…Six weeks after contusion SCI, animals exhibited increased H-reflex responsiveness (i.e., shown by reduced rate-dependent depression, or RDD). Histological assessment in these animals demonstrated that ␣-motor neurons located below the level of injury within the L4 -L5 spinal segments had an increase in dendritic spine density, a significant redistribution of spines along dendrites, and increased dendritic spine head diameter, morphological profiles consistent with those shown to contribute to increased neuronal excitability (Pongracz 1985;Tan et al 2009). In contrast, above the level of injury, we observed an absence of exaggerated H-reflex response, reduced dendritic spine densities, a close-to-normal distribution of spines, and normal dendritic spine length and head diameter.…”

“…Dendritic spines, micron-sized structures that are sites of postsynaptic activity, regulate the efficacy of synaptic transmission and can thereby alter the electrical information passing through circuit pathways (Bourne and Harris 2007;Calabrese et al 2006;Pongracz 1985;Segev and Rall 1988;Tan et al 2009). Localized increases in synaptic strength through the de novo formation and development of postsynaptic dendritic spines constitute a persistent structural basis for learning and memory in the central nervous system (Xu et al 2009;Yuste and Bonhoeffer 2001).…”