Postsynaptic deregulation in GAP-43 heterozygous mouse barrel cortex.
Formation of whisker-related barrels in primary somatosensory cortex (S1) requires communication between presynaptic thalamocortical afferents (TCAs) and postsynaptic cortical neurons. GAP-43 is crucially involved in targeting TCAs to postsynaptic S1 neurons but its influence on the interactions between these 2 elements has not been explored. Here, we tested the hypothesis that reduced early expression of presynaptic GAP-43 (GAP-43 heterozygous [HZ] mice) alters postsynaptic differentiation of barrel cells. We found a transient increase in cytochrome oxidase staining between P6 and P14 in HZ animals, indicative of increased metabolic activity in barrel cortex during this time. Golgi impregnation and microtubule-associated protein 2 immunohistochemistry showed anomalous dendritic patterning in GAP-43 HZ cortex at P5, with altered dendritic length and branching and abnormal retention of dendrites that extend into developing septa. This deficiency was no longer apparent at P7, suggesting partial recovery of dendritic pruning processes. Finally, we showed early defects in synaptogenesis from P4 to P5 with increased colocalization of NR1 and GluR1 staining in HZ mice. By P7, this colocalization had normalized to wild type levels. Taken together, our findings suggest abnormal postsynaptic differentiation in GAP-43 HZ cortex during early barrel development, followed by adaptive compensation and partial phenotypic rescue.
Kelly
Emily A
EA
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Tremblay
Marie-Eve
ME
McCasland
James S
JS
Majewska
Ania K
AK
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D003576:Electron Transport Complex IV / Q000378:metabolism; D019922:GAP-43 Protein / Q000172:deficiency / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016622:Silver Staining; D013003:Somatosensory Cortex / Q000254:growth & development / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014738:Vibrissae / Q000294:innervation*
D003576:Electron Transport Complex IV; D019922:GAP-43 Protein; D008869:Microtubule-Associated Proteins; D018091:Receptors, AMPA