Effects of elevated serotonin levels on patterns of GAP-43 expression during barrel development in rat somatosensory cortex.
Elevating cortical serotonin (5-HT) in rats with clorgyline, a monoamine oxidase A (MAO(A)) inhibitor, from postnatal day (P-0) to P-6 delays the organization of thalamocortical afferent fibers into a vibrissae-related pattern in the somatosensory cortex (S-I). Despite continued elevation of cortical 5-HT through P-8, the thalamocortical fibers do form, albeit with some delay, a characteristic vibrissae pattern of barrels in layer IV of S-I by P-8. The growth-associated protein, GAP-43, is transiently expressed in developing S-I cortex of normal rats in a vibrissae related pattern until P-7. After P-7, GAP-43 expression is reduced in the barrel centers and increased in the septa. The present study evaluated the effect of elevated 5-HT levels on the distribution of GAP-43 immunoreactivity in S-I. We employed 5-HT immunocytochemistry and 1,1'-dioctadecyl-3,3,3",3'-tetramethylindocarbocyanine perchlorate (DiI) labeling of thalamic radiations to confirm a 'barrelless' phenotype in P-6 clorgyline-treated animals and a recovered barrel pattern in treated animals allowed to survive until P-8 and P-10. GAP-43 immunocytochemistry was used to evaluate the cortical distribution of this protein in similarly treated littermates. Continuous inhibition of MAO(A) from P-0 to P-6 resulted in a corresponding loss of the GAP-43 vibrissae-related pattern at P-6. Despite continued elevation of cortical 5-HT until P-8 and P-10, the characteristic vibrissae-complementary pattern of GAP-43 emerged with expression concentrated in the septa and rows. GAP-43 vibrissae-related thalamocortical axon pattern never appeared in the clorgyline-treated animals. Thus, while elevated 5-HT delays development of a vibrissae-related pattern of thalamocortical afferents, it does not appear to alter the time when a GAP-43 vibrissae-related complementary pattern emerges.
Kesterson
Kay L
KL
Department of Anatomy and Neurobiology, Medical College of Ohio, 3000 Arlington Avenue, Toledo, OH 43614, USA. kkesterson@mco.edu
Lane
Richard D
RD
Rhoades
Robert W
RW
D000818:Animals; D000831:Animals, Newborn; D002232:Carbocyanines; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D013788:Thalamus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D014738:Vibrissae / Q000294:innervation / Q000502:physiology
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D019922:GAP-43 Protein; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D003010:Clorgyline