Convergence of nicotine-induced and auditory-evoked neural activity activates ERK in auditory cortex

Authors

  • Hideki D. Kawai,

    1. Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California
    2. Department of Bioinformatics, Faculty of Engineering, Soka University, Hachiouji, Tokyo, Japan
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    • H.D.K. and M.L. contributed equally to this work.

  • Maggie La,

    1. Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California
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    • H.D.K. and M.L. contributed equally to this work.

  • Ho-An Kang,

    1. Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California
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  • Yusuke Hashimoto,

    1. Department of Bioinformatics, Faculty of Engineering, Soka University, Hachiouji, Tokyo, Japan
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  • Kevin Liang,

    1. Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California
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  • Ronit Lazar,

    1. Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California
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  • Raju Metherate

    Corresponding author
    • Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California
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Correspondence to: Raju Metherate, Department of Neurobiology and Behavior, University of California, Irvine, 2205 McGaugh Hall, Irvine, CA 92697-4550, USA. E-mail: raju.metherate@uci.edu

ABSTRACT

Enhancement of sound-evoked responses in auditory cortex (ACx) following administration of systemic nicotine is known to depend on activation of extracellular-signaling regulated kinase (ERK), but the nature of this enhancement is not clear. Here, we show that systemic nicotine increases the density of cells immunolabeled for phosphorylated (activated) ERK (P-ERK) in mouse primary ACx (A1). Cortical injection of dihydro-β-erythroidine reduced nicotine-induced P-ERK immunolabel, suggesting a role for nicotinic acetylcholine receptors located in A1 and containing α4 and β2 subunits. P-ERK expressing cells were distributed mainly in layers 2/3 and more sparsely in lower layers, with many cells exhibiting immunolabel within pyramidal-shaped somata and proximal apical dendrites. About one-third of P-ERK positive cells also expressed calbindin. In the thalamus, P-ERK immunopositive cells were found in the nonlemniscal medial geniculate (MG) and adjacent nuclei, but were absent in the lemniscal MG. Pairing broad spectrum acoustic stimulation (white noise) with systemic nicotine increased P-ERK immunopositive cell density in ACx as well as the total amount of P-ERK protein, particularly the phosphorylated form of ERK2. However, narrow spectrum (tone) stimulation paired with nicotine increased P-ERK immunolabel preferentially at a site within A1 where the paired frequency was characteristic frequency (CF), relative to a second site with a spectrally distant CF (two octaves above or below the paired frequency). Together, these results suggest that ERK is activated optimally where nicotinic signaling and sound-evoked neural activity converge. Synapse 67:455–468, 2013. © 2013 Wiley Periodicals, Inc.

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