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Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

  • Neuroscience
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Abstract

Acetylcholine modulates the function of the cochlear nucleus via several pathways. In this study, the effects of cholinergic stimulation were studied on the cytoplasmic Ca2+ concentration of granule neurones of the rat dorsal cochlear nucleus (DCN). Ca2+ transients were recorded in Oregon-Green-BAPTA 1-loaded brain slices using a calcium imaging technique. For the detection, identification and characterisation of the Ca2+ transients, a wavelet analysis-based method was developed. Granule cells were identified on the basis of their size and localisation. The action potential-coupled character of the Ca2+ transients of the granule cells was established by recording fluorescence changes and electrical activity simultaneously. Application of the cholinergic agonist carbamyl-choline (CCh) significantly increased the frequency of the Ca2+ transients (from 0.37 to 6.31 min−1, corresponding to a 17.1-fold increase; n = 89). This effect was antagonised by atropine, whereas CCh could still evoke an 8.3-fold increase of the frequency of the Ca2+ transients when hexamethonium was present. Using immunolabelling, the expression of both type 1 and type 3 muscarinic receptors (M1 and M3 receptors, respectively) was demonstrated in the granule cells. Application of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (an M3-specific antagonist) prevented the onset of the CCh effect, whereas an M1-specific antagonist (pirenzepine) was less effective. We conclude that cholinergic stimulation increases the activity of granule cells, mainly by acting on their M3 receptors. The modulation of the firing activity of the granule cells, in turn, may modify the firing of projection neurones and may adjust signal processing in the entire DCN.

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Acknowledgments

This work was supported by a grant from the Hungarian Scientific Research Fund (OTKA K-72812), by an NHMRC (National Health and Medical Research Council) Australia Fellowship Grant awarded to Dr. George Paxinos (grant no. 568605) and by the Australian Research Council Thinking Systems Initiative (TS0669860).

Ethical considerations

The protocols used in the animal experiment were approved by the Committee of Animal Research of the University of Debrecen and by the Animal Care and Ethics Committee of The University of New South Wales, and they were in accordance with the relevant national and institutional guidelines on the care of research animals.

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The authors declare that they have no conflict of interest.

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Correspondence to Géza Szücs.

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Kőszeghy, Á., Vincze, J., Rusznák, Z. et al. Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study. Pflugers Arch - Eur J Physiol 463, 829–844 (2012). https://doi.org/10.1007/s00424-012-1103-1

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  • DOI: https://doi.org/10.1007/s00424-012-1103-1

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