Postnatal development of nicotinic acetylcholine receptor signaling in the cerebral cortex

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Reliable synaptic transmission is critical for the orderly development of sensory cortical circuits. In order for this to occur, receptors need to cluster at strategic sites in neurons to control net excitability. Disruptions in receptor trafficking and clustering can lead to profound impairments in brain function. Thus far, most studies of receptor clustering have focused on cholinergic synapses at the neuromuscular junction or glutamate and GABA receptors in the developing central nervous system. However, with the development of deep tissue 2-photon imaging and genetic engineering of fluorescently tagged nicotinic receptors, it is now possible to track nAChR trafficking and clustering in the intact postnatal brain. Preliminary fluorescence and electron microscopy data from my lab clearly indicate that there are dramatic changes in distribution of nAChR in the somatosensory cortex during a critical period of post-natal development where normal sensory cortical function is established. The proposed experiments seek to understanding the developmental time table and cell specificity of nAChR trafficking, what binding proteins regulate this process and ultimately, what is the functional significance of proper nAChR development and signalling in the cerebral cortex?