Specification of neuropeptide Y phenotype in visual cortical neurons by leukemia inhibitory factor

Building the complex mammalian neocortex requires appropriate numbers of ne urochemically specified neurons. It is not clear how the highly diverse cor tical interneurons acquire their distinctive phenotypes, The lack of geneti c determination implicates environmental factors in this selection and spec ification process. We analysed, in organotypic visual cortex cultures, the specification of neurons expressing neuropeptide Y (NPY), a potent anticonv ulsant, Endogenous brain-derived neurotrophic factor and neurotrophin 4/5 p lay no role in early NPY phenotype specification. Rather, the decision to e xpress NPY is made during a period of molecular plasticity during which dif ferentiating neurons with the potential to express NPY compete for the cyto kine leukemia inhibitory factor which is produced in the cortex, but is neg atively regulated by thalamic afferences, The neurons that fail in this com petition are parvalbuminergic basket and chandelier neurons, which express NPY transiently, but will not acquire a permanent NPY expression, They swit ch into a facultative NPY expression mode, and remain responsive to the neu rotrophins which modulate NPY expression later in development.