Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 37, Pages 8555-8566Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1983-05.2005
Keywords
nicotinic receptors; cholinergic synaptic transmission; high-affinity choline transporter; muscarinic receptors; autonomic nervous system; synapse formation
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In vertebrates, synaptic activity exerts an important influence on the formation of neural circuits, yet our understanding of its role in directing presynaptic and postsynaptic differentiation during synaptogenesis is incomplete. This study investigates how activity influences synaptic differentiation as synapses mature during early postnatal life. Specifically, we ask what happens to presynaptic terminals when synapses develop without functional postsynaptic receptors and without fast synaptic transmission. To address this issue, we investigated cholinergic nicotinic synapses in sympathetic ganglia of mice with a null mutation for the alpha 3 nicotinic ACh receptor gene. Disrupting the alpha 3 gene completely eliminates fast excitatory synaptic potentials on postganglionic sympathetic neurons, establishing a crucial role for alpha 3-containing postsynaptic receptors in synaptic transmission. Interestingly, the preganglionic nerve terminals form morphologically normal synapses with sympathetic neurons, and these synapses persist without activity in postnatal animals. Surprisingly, when stimulating the preganglionic nerve at physiological rates, we discovered a significant decrease in ACh output from the presynaptic terminals in these alpha 3(-/-) sympathetic ganglia. We show that this decrease in ACh output from the presynaptic terminals results, in part, from a lack of functional high-affinity choline transporters. We conclude the following: (1) fast synaptic transmission in mammalian SCG requires alpha 3 expression; (2) in the absence of activity, the preganglionic nerve forms synapses that appear morphologically normal and persist for several weeks; and (3) to sustain transmitter release, developing presynaptic terminals require an activity-dependent retrograde signal.
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