BLOCKADE OF GABAERGIC INHIBITION REVEALS REORDERED CORTICAL SOMATOTOPIC MAPS IN RATS THAT SUSTAINED NEONATAL FORELIMB REMOVAL

A previous study from this laboratory demonstrated that forelimb remov al at birth results in invasion of the cuneate nucleus (CN) by sciatic nerve axons and the development of CN cells including thalamic projec tion neurons with receptive fields that include both the forelimb stum p and the hindlimb. However, recordings from unit clusters in lamina I V of the primary somatosensory cortex (SI) of these animals revealed t he presence of only a very few sites in the forelimb stump representat ion where responses to hindlimb stimulation could also be recorded. In the present study we tested the possibility that input from the hindl imb was suppressed in lamina IV of the cortical stump representation v ia GABAergic inhibitory mechanisms by mapping this cortical region, ap plying the gamma-aminobutyric acid-A (GABA(A)) and GABA(B) receptor an tagonists bicuculline and phaclofen (50 mu M each), and then remapping the same sites. In six neonatally manipulated rats, 15 of 242 sites ( 6.2%) in the stump representation responded to hindlimb stimulation be fore GABA receptor blockade and 107 (44.2%) of the same sites responde d to stimulation of the hindlimb during blockade (P < 0.05). In six no rmal adult rats, 7 of 264 sites (2.7%) in the forelimb representation responded to hindlimb stimulation before the application of bicucullin e and phaclofen. During GABA receptor blockage, 31 of these sites (11. 7%) responded to such stimulation (P < 0.02 us. the untreated normal c ortex and P < 0.01 vs. the neonatally manipulated rats treated with GA BA blockers). To specifically test the role of GABA(A) versus GABA(B) receptors in the inhibition of hindlimb input to the SI stump represen tation in rats that sustained neonatal forelimb removal, either bicucu lline or phaclofen alone was applied to SI in nine neonatally manipula ted animals. In four rats treated with bicuculline, 12 of 184 sites (6 .5%) in the stump representation responded to hindlimb stimulation bef ore treatment and 61 of 184 sites (33.2%) responded to such stimulatio n during application (P < 0.01). In animals (n = 5) treated with phacl ofen, 18 of 251 sites (7.2%) responded to hindlimb stimulation before treatment and 64 of these sites (25.5%) responded to such stimulation during application (P < 0.05). There was no significant difference bet ween the results obtained with bicuculline alone, phaclofen alone, or the two GABA blockers delivered together(P > 0.05). These results indi cate that hindlimb input to the portion of SI representing the forelim b stump is functionally suppressed in rats that have sustained neonata l forelimb removal and that GABAergic inhibition, mediated by both GAB A(A) and GABA(B) receptors, is involved in this process.