Progressive elevations in AMPA and GABAA receptor levels in deafferented somatosensory cortex

Abstract

Restricted receptive fields (RFs), a hallmark of mature sensory systems, are actively maintained by a balance between ascending excitation and local inhibition in the cortex. Deafferentation disrupts this balance, allowing a sequence of changes in neuronal response properties that culminate in the reorganization of cortical RFs. To explore the molecular basis of deafferentation-induced RF reorganization, we tracked changes in AMPA receptor (AMPAR), NMDA receptor (NMDAR) and GABAA receptor (GABAAR) levels in the deafferented somatosensory cortex of adult raccoons following single-digit amputation. In synaptoneurosomes prepared from deafferented cortex, we observe a significant increase in AMPARs, but no change in NMDARs, 1-9 days post-deafferentation, coincident with the appearance of new excitatory inputs and enlarged RFs. We observe a significant increase in GABAARs 2-7 weeks post-deafferentation, coincident with a return of inhibitory input and shrinking RFs. These experience-dependent changes in the levels of the major cortical ionotropic receptors were transient, returning to pre-experimental baseline by > or = 17 weeks post-deafferentation, when RFs return to original size, but are remapped to different loci. This suggests that deafferentation-induced cortical reorganization may be generated by activity-dependent potentiation of weak excitatory synapses, followed by an increase in the strength of inhibitory synapses, resulting in finely tuned, remapped cortical RFs.