A transgenic mouse model reveals fast nicotinic transmission in hippocampal pyramidal neurons.

A transgenic mouse model reveals fast nicotinic transmission in hippocampal pyramidal neurons.
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DOI:
10.1111/j.1460-9568.2011.07671.x
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发表时间:
2011-05
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Vijayaraghavan S
Vijayaraghavan S
中科院分区:
其他
文献类型:
--
作者:
Grybko MJ;Hahm ET;Perrine W;Parnes JA;Chick WS;Sharma G;Finger TE;Vijayaraghavan S

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The relative contribution, to brain cholinergic signaling, by synaptic- and diffusion-based mechanisms remains to be elucidated. In this study, we examined the prevalence of fast nicotinic signaling in the hippocampus. We describe a mouse model where cholinergic axons are labeled with the tauGFP fusion protein driven by the choline acetyltransferase (ChAT) promoter. The model provides for the visualization of individual cholinergic axons at greater resolution than other available models and techniques, even in thick, live, slices. Combining calcium imaging and electrophysiology, we demonstrate that local stimulation of visualized cholinergic fibers results in rapid EPSCs mediated by the activation of α7-subunit containing nicotinic receptors (α7-nAChRs) on CA3 pyramidal neurons. These responses were blocked by the α7-nAChR antagonist methyllycaconitine (MLA) and potentiated by the receptor specific allosteric modulator 1-(5-chloro-2,4- dimethoxy-phenyl)-3-(5-methyl-isoxanol-3-yl)-urea (PNU-120596). Our results suggest, for the first time, that synaptic nAChRs can modulate pyramidal cell plasticity and development. Fast nicotinic transmission might play a greater role in cholinergic signaling than previously assumed. We provide a model for the examination of synaptic properties of basal forebrain cholinergic innervation in the brain.
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