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Nicotinic control of axon excitability regulates thalamocortical transmission

Nature Neuroscience volume 10, pages 1168–1175 (2007)Cite this article

Abstract

The thalamocortical pathway, a bundle of myelinated axons that arises from thalamic relay neurons, carries sensory information to the neocortex. Because axon excitation is an obligatory step in the relay of information from the thalamus to the cortex, it represents a potential point of control. We now show that, in adult mice, the activation of nicotinic acetylcholine receptors (nAChRs) in the initial portion of the auditory thalamocortical pathway modulates thalamocortical transmission of information by regulating axon excitability. Exogenous nicotine enhanced the probability and synchrony of evoked action potential discharges along thalamocortical axons in vitro, but had little effect on synaptic release mechanisms. In vivo, the blockade of nAChRs in the thalamocortical pathway reduced sound-evoked cortical responses, especially those evoked by sounds near the acoustic threshold. These data indicate that endogenous acetylcholine activates nAChRs in the thalamocortical pathway to lower the threshold for thalamocortical transmission and to increase the magnitude of sensory-evoked cortical responses. Our results show that a neurotransmitter can modulate sensory processing by regulating conduction along myelinated thalamocortical axons.

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Figure 1: Postsynaptic and axon spike responses to stimulation of adult thalamocortical axons.
Figure 2: Nicotine enhances success rate for thalamocortical EPSCs.
Figure 3: Nicotine enhances success rate for axon spikes in subcortical white matter.
Figure 4: Minimal EPSCs in thalamocortical slices with MGv severed.
Figure 5: Nicotine decreases the latency and latency variability of axon spikes.
Figure 6: Blockade of nAChRs in thalamic white matter in vivo delays onset latency and decreases amplitude of tone-evoked responses in auditory cortex.

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Acknowledgements

We thank M. Raastad for technical advice on axon spike recordings, T.J. Carew for comments on an earlier version of manuscript and H.J. Mun and Y. Hu for technical assistance. Supported by US National Institutes of Health grants (DC02967 and DA12929 to R.M., and DC08204 to H.K.).

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Authors and Affiliations

  1. Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, 2205 McGaugh Hall, Irvine, 92697-4550, California, USA

    Hideki Kawai, Ronit Lazar & Raju Metherate

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  1. Hideki Kawai
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Contributions

H.K. conducted the in vitro and in vivo experiments and data analysis. R.L. contributed to the in vivo experiments and data analysis. R.M. supervised the project. H.K. and R.M. co-wrote the manuscript.

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Correspondence to Raju Metherate.

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The authors declare no competing financial interests.

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Kawai, H., Lazar, R. & Metherate, R. Nicotinic control of axon excitability regulates thalamocortical transmission. Nat Neurosci 10, 1168–1175 (2007). https://doi.org/10.1038/nn1956

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