Extrasynaptic α7-nicotinic acetylcholine receptor expression in developing neurons is regulated by inputs, targets, and activity

Abstract

α7-Nicotinic acetylcholine receptors (nAChRs) are widely expressed in the vertebrate nervous system. α7-nAChR functions include postsynaptic transmission, modulating neurotransmitter release, reinforcing nicotine addiction, and a role in neurological disorders, such as schizophrenia and Alzheimer's disease. In chick parasympathetic ciliary ganglion (CG) neurons, α7-nAChRs are excluded from the synapse and localize perisynaptically. Despite their extrasynaptic distribution, the highly Ca2--permeable α7-nAChRs have important synapse-related Ca2+-dependent signaling functions in the CG. We show here that the synaptic partners regulate α7-nAChR expression during synapse formation in embryonic CG neurons in situ. The absence of inputs and target tissues cause reductions in α7-nAChR mRNA and protein levels that primarily resemble those seen for synaptic α3-nAChRs. However, there is a difference in their regulation. α7-nAChR levels are downregulated by reduced activity, whereas α3-nAChR levels are not. We propose that the activity-dependent regulation of extrasynaptic α7-nAChR levels may be an important mechanism for postsynaptic CG neurons to detect changes in presynaptic activity levels and respond with Ca2+-dependent plasticity changes in gene expression.