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Cerebral Cortex April 2004; 14:432-440
© Oxford University Press 2004

Article

GABAA Receptors Reorganize when Layer 4 in Ferret Somatosensory Cortex is Disrupted by Methylazoxymethanol (MAM)

Beata Jablonska1, Adam L. Smith2, Sidney L. Palmer1, Stephen C. Noctor3 and Sharon L. Juliano1,3

1 Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, MD 20814, USA, 2 University Laboratory of Physiology, Oxford OX1-3PT, UK, 3 Program in Neuroscience, USUHS, Bethesda, MD 20814, USA

We established a model of cortical development that arrests the birth of layer 4 cells by injecting methylazoxymethanol (MAM) on embryonic day 33 (E33) in ferrets. This leads to adult somatosensory cortex with a very thin layer 4. Earlier, we determined the relative absence of layer 4 changed the growth and differentiation of the somatosensory cortex and the growth of thalamic afferents into the cortical plate. To identify other features of cortical organization that might be altered after MAM treatment, we assessed the distribution of selected excitatory and inhibitory receptors in area 3b of ferret somatosensory cortex. Initial screening revealed the distribution of several excitatory receptors (NMDA, AMPA, kainate) in E33 MAM-treated cortex was similar to that in normal adult animals. In contrast, the binding pattern of inhibitory GABAA receptors was altered in MAM-treated cortex. Normally, GABAA receptors densely locate in central layers of cortex. In E33 MAM-treated animals, GABAA receptor binding extended superficially, covering a broader area of cortex. Further experiments using antibodies directed against GABAA{alpha} receptors disclosed that pan {alpha} GABAA receptors strongly localize to layer 4 in normal area 3b. In E33 MAM-treated cortex, however, GABAA{alpha} receptors extend outside and are located above and below the very thin layer 4. The redistribution of inhibitory receptors suggests that layer 4 plays an important role in regulating thalamic terminations and also in the resulting ability to refine processing of incoming stimuli.


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