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Neuron. 2009 Jan 29;61(2):272-86. doi: 10.1016/j.neuron.2008.11.025.

An activity-dependent retrograde signal induces the expression of the high-affinity choline transporter in cholinergic neurons.

Author information

1
Department of Physiology, McGill University, Montreal, H3G 1Y6 Quebec, Canada.

Abstract

A well-accepted view of developing circuits is that synapses must be active to mature and persist, whereas inactive synapses remain immature and are eventually eliminated. We question this long-standing view by investigating nonfunctional cholinergic nicotinic synapses in the superior cervical ganglia (SCG) of mice with a disruption in the alpha3 nicotinic receptor (nAChR) subunit gene, a gene essential for fast synaptic transmission in sympathetic ganglia. Using imaging and electrophysiology, we show that synapses persist for at least 2-3 months without postsynaptic activity; however, the presynaptic terminals lack high-affinity choline transporters (CHTs), and as a result, they are quickly depleted of transmitter. Moreover, we demonstrate with rescue experiments that CHT is induced by signals downstream of postsynaptic activity, converting immature terminals to mature terminals capable of sustaining transmitter release in response to high-frequency or continuous firing. Importantly, postsynaptic neurons must be continually active to maintain CHT in presynaptic terminals.

PMID:
19186169
DOI:
10.1016/j.neuron.2008.11.025
[Indexed for MEDLINE]
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