Acetylcholinesterase promotes neurite elongation, synapse formation, and surface expression of AMPA receptors in hippocampal neurones.
Here we show that chronic application of low concentrations (0.01-0.05 U/ml) or a single application of 1-5 U/ml acetylcholinesterase (AChE) promotes the extension of neuronal processes, synapse formation, and alpha-amino-3-hydroxy-5-methylisoxazolepropionate receptor (AMPAR) surface expression in both embryonic and postnatal hippocampal cultures. The total number of AMPARs was unchanged but the proportion of receptors that were surface-expressed, predominantly at synapses, was approximately doubled following AChE treatment. Blockade of the peripheral anionic site of endogenous AChE in the cultures dramatically reduced neurite outgrowth but did not alter the appearance of synaptic markers SV2a and PSD95. These results indicate that AChE is necessary for normal dendrite and axon formation in hippocampal neurones and suggest that it may also play a role in excitatory synapse development, plasticity, and remodelling.
Olivera
Silvia
S
MRC Centre for Synaptic Plasticity, Anatomy Department, School of Medical Sciences, University of Bristol, University Walk, UK.
Rodriguez-Ithurralde
Daniel
D
Henley
Jeremy M
JM
D000110:Acetylcholinesterase / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000201:enzymology; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide / Q000494:pharmacology; D015415:Biomarkers; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D003712:Dendrites / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D018091:Receptors, AMPA; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide; D000110:Acetylcholinesterase