Related Experiment Videos
Effects of elevated serotonin levels on patterns of GAP-43 expression during barrel development in rat somatosensory
Kay L Kesterson1, Richard D Lane, Robert W Rhoades
1Department of Anatomy and Neurobiology, Medical College of Ohio, 3000 Arlington Avenue, Toledo, OH 43614, USA. kkesterson@mco.edu
Insights
Elevating serotonin in developing rats delays thalamocortical axon patterning. However, the growth-associated protein GAP-43 still emerges in a complementary pattern, indicating distinct developmental pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurochemistry
Background:
- Cortical serotonin (5-HT) plays a crucial role in brain development.
- Monoamine oxidase A (MAO(A)) inhibitors elevate 5-HT levels.
- Thalamocortical pathway organization is critical for sensory processing.
Purpose of the Study:
- To investigate the impact of elevated cortical serotonin on thalamocortical axon patterning in the rat somatosensory cortex (S-I).
- To examine the effect of sustained 5-HT elevation on the expression and distribution of growth-associated protein 43 (GAP-43).
Main Methods:
- Rats were treated with clorgyline (MAO(A) inhibitor) from postnatal day 0 to 6 to elevate cortical 5-HT.
- 5-HT immunocytochemistry and DiI labeling were used to assess thalamocortical organization.
- GAP-43 immunocytochemistry evaluated protein distribution in the S-I cortex.
Main Results:
- Elevated 5-HT delayed the formation of vibrissae-related thalamocortical barrel patterns in S-I.
- Despite delayed axon patterning, GAP-43 expression eventually adopted a complementary pattern, concentrated in septa and rows.
- The characteristic GAP-43 vibrissae-related thalamocortical axon pattern did not emerge in clorgyline-treated rats.
Conclusions:
- Sustained elevation of cortical 5-HT during early development delays thalamocortical axon patterning in S-I.
- The emergence of the GAP-43 complementary pattern is not prevented by elevated 5-HT, suggesting independent regulation.
- These findings highlight the complex interplay between neurotransmitters and molecular markers in guiding neural circuit development.
Abstract:
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.