Extrasynaptic alpha 7-nicotinic acetylcholine receptor expression in developing neurons is regulated by inputs, targets, and activity

J Neurosci. 2002 Sep 15;22(18):8101-9. doi: 10.1523/JNEUROSCI.22-18-08101.2002.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Count
  • Chick Embryo
  • Denervation
  • Ganglia, Parasympathetic / cytology
  • Ganglia, Parasympathetic / embryology
  • Ganglia, Parasympathetic / metabolism
  • Ganglia, Sympathetic / cytology
  • Ganglia, Sympathetic / embryology
  • Ganglia, Sympathetic / metabolism
  • Gene Expression Regulation, Developmental / physiology*
  • Neuronal Plasticity / physiology
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Subunits
  • RNA, Messenger / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Sensory Deprivation / physiology
  • Synapses / physiology
  • Synaptic Transmission / physiology
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Protein Subunits
  • RNA, Messenger
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • nicotinic receptor subunit alpha3
  • Calcium