Extrasynaptic alpha 7-nicotinic acetylcholine receptor expression in developing neurons is regulated by inputs, targets, and activity.
Alpha7-nicotinic acetylcholine receptors (nAChRs) are widely expressed in the vertebrate nervous system. alpha7-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, alpha7-nAChRs are excluded from the synapse and localize perisynaptically. Despite their extrasynaptic distribution, the highly Ca2+-permeable alpha7-nAChRs have important synapse-related Ca2+-dependent signaling functions in the CG. We show here that the synaptic partners regulate alpha7-nAChR expression during synapse formation in embryonic CG neurons in situ. The absence of inputs and target tissues cause reductions in alpha7-nAChR mRNA and protein levels that primarily resemble those seen for synaptic alpha3-nAChRs. However, there is a difference in their regulation. alpha7-nAChR levels are downregulated by reduced activity, whereas alpha3-nAChR levels are not. We propose that the activity-dependent regulation of extrasynaptic alpha7-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.
Brumwell
Craig L
CL
Department of Neuroscience, Tufts University, Sackler School of Biomedical Sciences, Boston, Massachusetts 02111, USA.
Johnson
James L
JL
Jacob
Michele H
MH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002642:Chick Embryo; D003714:Denervation; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012683:Sensory Deprivation / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002118:Calcium; D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor