Receptor autoradiographic correlates of deafferentation‐induced reorganization in adult primate somatosensory cortex

Abstract

The primate somatosensory system provides an excellent model system with which to investigate adult neural plasticity. We have previously shown that transection of the median and ulnar nerves is followed by an expansion in the representation of radial nerve skin, and that this plasticity proceeds in stages. Immediately following nerve injury, new receptive fields are "unmasked" in a fraction of the affected cortex. The remaining deprived cortex regains responsiveness to tactile stimulation over the following days to weeks. Given these progressive changes, it has been suggested that different mechanisms might account for the earlier and later phases of reorganization. In the present experiments, we have quantified receptor autoradiographic binding data for GABA A and GABA B , AMPA, and NMDA receptors in the primary somatosensory cortices of adult squirrel monkeys at four post-nerve injury survival durations: immediately (1-3 hr), 3-days, 1-month, and 2-months. We find dramatic reductions in GABA A binding in layer IV within hours following nerve injury, and this reduction is maintained across all survival durations. This finding is consistent with the idea that the earliest reorganizational changes are due to a relaxation in tonic inhibitory mechanisms permitting the expression of formerly subthreshold receptive fields. GABA B receptor binding is decreased in layer IV by 1 month after nerve injury, while binding for AMPA receptors is increased in layer IV by this time. These findings are consistent with our previous suggestion that the second stage of reorganization proceeds via mechanisms comparable to those revealed to account for NMDA-dependent long-term potentiation in the hippocampus.

Optogenetic-guided cortical plasticity after nerve injury

“…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). Moreover, increases in motor-evoked potential in the motor cortical representations contralateral and ipsilateral to the nerve injury in human subjects were blocked after administration of GABA agonists (24).…”

Temporary off-frequency listening after noise trauma

“…Since the number of cochlear nerve fibers is around 20,000, a permanent influx of a minimum of 1 million of spikes/sec is sent toward the auditory centers. Any decrease of this spontaneous and stimulusinduced peripheral activity, due to a lesioned sensory epithelium (Liberman and Dodds, 1984;Heinz and Young, 2004), could induce a decrease in central inhibition (Garraghty and Muja, 1996;Garraghty et al, 2006). Ultimately, the release from inhibition, if sufficient, could result in neural hyperactivity and tonotopic map reorganization (Snyder et al, 2000;Snyder and Sinex, 2002;Snyder et al, 2008;Noreña, 2011 for a review).…”

Reorganization of Retinotopic Maps after Occipital Lobe Infarction

“…Early changes may be due to unmasking of latent inputs due to a loss of GABA (Garraghty and Kaas 1991) but there are also later changes in AMPA receptors (Garraghty et al 2006) and in the morphology of the dendrites of neurons in the affected area (Churchill et al 2004). …”