Morphological and Physiological Plasticity of Spinal Lamina II GABA Neurons Is Induced by Sciatic Nerve Chronic Constriction Injury in Mice

Abstract

Mice with transgenic insertion of code for enhanced green fluorescent protein (EGFP) at the locus for glutamic acid decarboxylase 67 (GAD67), one of two key enzymes for the synthesis of γ-aminobutyric acid (GABA) were used to test whether the morphological properties of these neurons show plasticity with nerve injury. Physiological properties and the delivery of intracellular label to EGFP-expressing lamina II neurons was done using whole-cell patch-clamp in spinal cord slices from sham and chronic constriction injury (CCI) mice. As well, whole cell recordings were made of non-EGFP labeled cells to ascertain changes in overall inhibitory signaling following CCI. The EGFP labeled neurons in both sham and CCI mice exhibited islet, central and vertical cell morphological profiles but no radial cell profiles were observed. The length of cell dendrites was found to be significantly shorter in CCI mice for all cell profile types. The longest neurites averaged 155.96 ± 18.29 μm in CCI mice compared to 334.93 ± 29.48 μm in sham control mice. No change was observed in either passive or evoked membrane properties of EGFP-expressing neurons in CCI versus sham mice. Meanwhile, the frequency of miniature inhibitory post-synaptic currents of non-EGFP expressing spinal lamina II neurons was significantly reduced. These results suggest that reduced inhibitory output from GABA neurons occurs with nerve injury in part due to altered cell morphology.

Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition

“…While these results are the first of their kind to demonstrate cytoarchitectural changes in models of chronic migraine, alterations in neuronal plasticity have been described previously in models of neuropathic pain. A mouse model of chronic constriction injury of the sciatic nerve reduced neurite length in GABA neurons within lamina II of the spinal cord [50]. Another group observed that following spared nerve injury, there were decreases in the number of branches and neurite length of hippocampal neurons but increases in spinal dorsal horn neurons [51].…”

Valproate reduces neuroinflammation and neuronal death in a rat chronic constriction injury model

“…pentobarbital sodium, and the sciatic nerve exposed by blunt dissection of the biceps femoris muscle, and dissected and freed proximal to the sciatic trifurcation. Three 4-0 chromic catgut ligatures 45 – 48 were loosely tied around the sciatic nerve until the rat’s hind limb briefly twitched. Both sides of the sciatic nerve were handled using the same procedure.…”

Central Nervous System Targets: Inhibitory Interneurons in the Spinal Cord

“…One hypothesis implicates the downregulation of the chloride ion transporter KCC2 following peripheral nerve injury [ 112 – 115 ], brought about by the release of brain-derived neurotrophic factor (BDNF) from axotomized afferents [ 116 , 117 ]. A reduction of KCC2 leads to disruption in chloride equilibrium, and this reduces the efficacy of inhibition mediated by the release of GABA and glycine in pain-transmitting neurons, whereas others have proposed that the reduced excitability of inhibitory interneurons and/or loss of their synaptic inputs are additional contributing factors [ 118 – 120 ].…”