Dendritic spine remodeling after spinal cord injury alters neuronal signal processing.
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.
Tan
Andrew M
AM
Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06516, USA.
Choi
Jin-Sung
JS
Waxman
Stephen G
SG
Hains
Bryan C
BC
D000200:Action Potentials; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003198:Computer Simulation; D049229:Dendritic Spines / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors