AMPA and GABAA/B receptor subunit expression in the cortex of adult squirrel monkeys during peripheral nerve regeneration

Abstract

The primate somatosensory neuroaxis provides a highly translational model system with which to investigate adult neural plasticity. Here, we report immunohistochemical staining data for AMPA and GABAA/B receptor subunits in the area 3b cortex of adult squirrel monkeys one and five months after median nerve compression. This method of nerve injury was selected because it allows unique insight into how receptor expression changes during the regeneration of the peripheral nerve. One month after nerve compression, the pattern of subunit staining provides evidence that the cortex enters a state of reorganization. GABA 1 receptor subunits are significantly down-regulated in layer IV, V, and VI. Glur2/3 AMPA receptor subunits and postsynaptic GABABR1b receptor subunits are up and down regulated respectively across all layers of cortex. After five months of recovery from nerve compression, the pattern of AMPA and GABAA/B receptor subunits remain significantly altered in a layer specific manner. In layer II/III, GluR1, GluR2/3, and GABA 1 subunit expression is significantly up-regulated while post synaptic GABABR1b receptor subunits are significantly down regulated. In layer VI, V, and VI the GluR2/3 and presynaptic GABABR1a receptor subunits are significantly up-regulated, while the postsynaptic GABABR1b receptor subunits remain significantly down-regulated. Taken together, these results suggest that following nerve injury the cortex enters a state of reorganization that has persistent effects on cortical plasticity even after partial or total reinnervation of the peripheral nerve.

AMPA and GABAA/B receptor subunit expression in the cuneate nucleus of adult squirrel monkeys during peripheral nerve regeneration

“…One month after nerve injury, the cortex [47] displays patterns of subunit expression that have been observed during somatosensory reorganization [26]. Currently we report a pattern of subunit expression in cuneate nucleus of these same animals that is very similar to that reported in infragranular cortex (Figure 1D).…”

“…Specifically, we have investigated receptor subunit specific changes that occur within the cortex and brainstem during recovery from peripheral nerve compression. [45, 46, 47, 51]. The current study extends these investigations of AMPA and GABA receptor subunits to the cuneate nucleus one and five months after nerve compression.…”

“…The pattern of AMPA and GABA A/B subunit expression within cuneate nucleus shows signs of reorganizational plasticity after one month of recovery, and continues to display significant changes in the pattern of subunit expression at a time when peripheral nerve regeneration has presumably reinnervated its original cutaneous inputs [59]. At both one and five months of recovery, the brainstem displays a pattern of subunit expression that is very similar to that seen in the corticofugal layers of cortex from the same animals [47]. This suggests that the cortex and brainstem are governed by homogeneous types of receptor plasticity following peripheral nerve injury, which further agrees with the functional roles that exist between them in vivo [63,64,65].…”

“…Methods for nerve injury, immunohistochemical staining, and data quantification have been previously described in detail [45,46,47,51]. All procedures were approved by the Indiana University Institutional Animal Care and Use Committee.…”

Sensory Input-Dependent Changes in Glutamatergic Neurotransmission- Related Genes and Proteins in the Adult Rat Trigeminal Ganglion

“…The GLUR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors was found to be differentially regulated in the visual cortex after monocular deprivation (Tropea et al, 2006). On the other hand, in the somatosensory adult cortex sustaining irreversible deafferentation by nerve transection, Mowery et al (2013, 2015) found no differences with controls in the expression of GLUR2/3; however, this subunit was permanently elevated in the cuneate nucleus, the main target for large mechanosensitive fibers arising from the lost nerves. Furthermore, the activation of the N -methyl- D -aspartate (NMDA) receptor was required for plastic changes to occur in the visual cortex following monocular deprivation in adult mice (Sawtell et al, 2003).…”