Nerve-injury Induced Changes to GluR1 and GluR2/3 Sub-unit Expression in Area 3b of Adult Squirrel Monkeys: Developmental Recapitulation?

Mowery, Todd M.; Garraghty, Preston E.

doi:10.3389/neuro.06.001.2009

Cited by 26 publications

(42 citation statements)

References 52 publications

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“…Modifications in synaptic transmission, yielding increased excitability in sensory and motor cortical representations both contralateral and ipsilateral to the injury, are an important neuroplasticity mechanism underlying cortical reorganization. For example, the extent of the somatosensory cortex reorganization after nerve injury was reduced after systemic administration of NMDA antagonist (50,51) and was tightly correlated to NMDA receptor-mediated plasticity (52). Increases in cortical excitability were also shown to be accompanied by increases in AMPA receptor autoradiographic binding (53) and decreases in GABA staining in the deprived S1 (53,54).…”

Section: Discussionmentioning

confidence: 85%

Optogenetic-guided cortical plasticity after nerve injury

Downey

Bar‐Shir

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Peripheral nerve injury causes sensory dysfunctions that are thought to be attributable to changes in neuronal activity occurring in somatosensory cortices both contralateral and ipsilateral to the injury. Recent studies suggest that distorted functional response observed in deprived primary somatosensory cortex (S1) may be the result of an increase in inhibitory interneuron activity and is mediated by the transcallosal pathway. The goal of this study was to develop a strategy to manipulate and control the transcallosal activity to facilitate appropriate plasticity by guiding the cortical reorganization in a rat model of sensory deprivation. Since transcallosal fibers originate mainly from excitatory pyramidal neurons somata situated in laminae III and V, the excitatory neurons in rat S1 were engineered to express halorhodopsin, a light-sensitive chloride pump that triggers neuronal hyperpolarization. Results from electrophysiology, optical imaging, and functional MRI measurements are concordant with that within the deprived S1, activity in response to intact forepaw electrical stimulation was significantly increased by concurrent illumination of halorhodopsin over the healthy S1. Optogenetic manipulations effectively decreased the adverse inhibition of deprived cortex and revealed the major contribution of the transcallosal projections, showing interhemispheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.recovery | amputation A lthough 20 million Americans suffer from peripheral nerve injury caused by trauma, metabolic, endocrine, and autoimmune disorders, there are few strategies to promote recovery. Surgical nerve repair and training of the injured limb are the classical rehabilitation approaches. Nevertheless, the clinical outcome in adults is generally poor, with persisting sensory dysfunction and pain (1).Recent evidence suggests that sensory dysfunctions caused by nerve injury should be attributable not only to the functional, cellular, and biochemical events occurring in peripheral nerve but also functional and anatomical changes occurring in cerebral cortical representations. It is well-documented in humans (2), non-human primates (3), cats (4), and rodents (5-7) that peripheral nerve injury can lead to expansion of neighboring cortical representation of peripheral regions within the affected (deprived) hemisphere (intrahemispheric neuroplasticity). Peripheral nerve injury and direct cortical lesions have been shown to also modify functional communication between cortical hemispheres (interhemispheric neuroplasticity) (8-19). Specifically, peripheral inputs normally evoking neuronal responses in the contralateral hemisphere cause inappropriate functional responses in the ipsilateral hemisphere. Previously, using singleunit electrophysiology recordings and juxtacellular labeling, it was shown that the inappropriate ipsilateral functional magnetic resonance imaging (fMRI) responses observed in deprived primary somatosensory cor...

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Section: Discussionmentioning

confidence: 85%

Optogenetic-guided cortical plasticity after nerve injury

Downey

Bar‐Shir

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Using this technique we previously reported that there are significant changes in AMPA and GABA A/B receptor subunits one week after median nerve compression, and that the resulting patterns of subunit immunostaining closely resemble ones found early in development (Mowery and Garraghty 2009; Mowery et. al.…”

Section: Introductionmentioning

confidence: 76%

“…Immunohistochemical quantification of tissue sections was carried out as previously described (Mowery and Garraghty, 2009) at 1480× under brightfield illumination using a microscope (Nikon Eclipse 80i; Nikon Instruments; Melville, NY, USA) and the Stereo Investigator software (MBF Bioscience; Williston, VT, USA). The Stereo Investigator software's luminance function (formerly densitometry/optical density) was used to quantify staining intensity of the traced contours (representative soma, neuropil, and white matter).…”

Section: Methodsmentioning

confidence: 99%

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

Mowery¹,

Walls²,

Garraghty

2013

Brain Research

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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.

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“…Furthermore, there is speculation that there are common mechanisms for the cortical changes that occur with injury, activity and experience (Overman and Carmichael 2013). There are even suggestions that changes in cortex may recapitulate ones that occur early in development (Mowery and Garraghty 2009). If so, training might indeed promote the rebuilding of circuits.…”

Section: Discussionmentioning

confidence: 99%

Reorganization of Retinotopic Maps after Occipital Lobe Infarction

Vaina

Soloviev

Calabro

et al. 2014

Journal of Cognitive Neuroscience

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We studied patient JS who had a right occipital infarct that encroached on visual areas V1, V2v and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this Motion Coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy subjects. Training on the Motion Coherence task generalized to another motion task, the Motion Discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT+) and in the kinetic occipital region (KO) as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8 and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere, of the patient or in either hemispheres of the healthy control subjects. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training.

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Nerve-injury Induced Changes to GluR1 and GluR2/3 Sub-unit Expression in Area 3b of Adult Squirrel Monkeys: Developmental Recapitulation?

Cited by 26 publications

References 52 publications

Optogenetic-guided cortical plasticity after nerve injury

Optogenetic-guided cortical plasticity after nerve injury

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

Reorganization of Retinotopic Maps after Occipital Lobe Infarction

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