RT Journal Article
SR Electronic
T1 A Null Mutation for the α3 Nicotinic Acetylcholine (ACh) Receptor Gene Abolishes Fast Synaptic Activity in Sympathetic Ganglia and Reveals That ACh Output from Developing Preganglionic Terminals Is Regulated in an Activity-Dependent Retrograde Manner
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8555
OP 8566
DO 10.1523/JNEUROSCI.1983-05.2005
VO 25
IS 37
A1 Siamak Rassadi
A1 Arjun Krishnaswamy
A1 Brigitte Pié
A1 Russell McConnell
A1 Michele H. Jacob
A1 Ellis Cooper
YR 2005
UL http://www.jneurosci.org/content/25/37/8555.abstract
AB 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 α3 nicotinic ACh receptor gene. Disrupting the α3 gene completely eliminates fast excitatory synaptic potentials on postganglionic sympathetic neurons, establishing a crucial role for α3-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 α3–/– 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 α3 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.