PHENOTYPE SPECIFICATION OF CORTICAL-NEURONS DURING A PERIOD OF MOLECULAR PLASTICITY

The transient expression of neuropeptide transmitters is a common feat ure of the developing cortex. We have now analysed the role of cortica l afferents in shaping the neurochemical architecture of rat visual co rtex using organotypic cultures. Deafferented cortex monocultures prep ared from newborn rats reveal a constant NPY mRNA expression in 6-8% o f all cortical neurons up to 90 days in vitro (DIV). In contrast, affe rent thalamocortical and corticocortical axonal innervation elicits a progressive reduction in the percentage of NPY mRNA expressing neurons from initially 6-8% in 30DIV cocultures to 2-3% and 3-4% respectively in 60DIV cocultures, which is maintained for up to 90DIV. This phenot ype restriction is not observed in only efferently connected corticoco llicular cocultures. Further, axonal innervation does not change the p ercentage of GAD mRNA-expressing neurons, which remains at 13% in mono -and cocultures. When feeding thalamocortical cocultures with monocult ure-conditioned medium between 3-20DIV followed by normal medium up to 60DIV, the phenotype restriction fails to occur in the cocultured cor tex. We conclude that cortex-derived factors secreted into the medium by a monoculture suppress the phenotype-restricting capacity of the af ferents, but only when present within the first 14DIV during the perio d of formation of axonal connections. To elucidate the nature of the c ortex-derived factors, brain-derived neurotrophic factor was applied t o the medium. When applied for the first 14DIV, it does not prevent th e phenotype restriction from occurring, This suggests that epigenetic factors such as axonal innervation and cortex-derived factors other th an brain-derived neurotrophic factor govern a phenotype decision in ne ocortical neurons during a period of molecular plasticity.