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• W2007067260 abstract "Activation of nicotinic acetylcholine receptors (nAChRs) by systemic nicotine enhances sensory-cognitive function and sensory-evoked cortical responses. Although nAChRs mediate fast neurotransmission at many synapses in the nervous system, nicotinic regulation of cortical processing is neuromodulatory. To explore potential mechanisms of nicotinic neuromodulation, we examined whether intracellular signal transduction involving mitogen-activated protein kinase (MAPK) contributes to regulation of tone-evoked responses in primary auditory cortex (A1) in the mouse. Systemic nicotine enhanced characteristic frequency (CF) tone-evoked current-source density (CSD) profiles in A1, including the shortest-latency (presumed thalamocortical) current sink in layer 4 and longer-latency (presumed intracortical) sinks in layers 2-4, by increasing response amplitudes and decreasing response latencies. Microinjection of the MAPK kinase (MEK) inhibitor U0126 into the thalamus, targeting the auditory thalamocortical pathway, blocked the effect of nicotine on the initial (thalamocortical) CSD component but did not block enhancement of longer-latency (intracortical) responses. Conversely, microinjection of U0126 into supragranular layers of A1 blocked nicotine's effect on intracortical, but not thalamocortical, CSD components. Simultaneously with enhancement of CF-evoked responses, responses to spectrally distant (nonCF) stimuli were reduced, implying nicotinic sharpening of frequency receptive fields, an effect also blocked by MEK inhibition. Consistent with these physiological results, acoustic stimulation with nicotine produced immunolabel for activated MAPK in A1, primarily in layer 2/3 cell bodies. Immunolabel was blocked by intracortical microinjection of the nAChR antagonist dihydro-β-erythroidine, but not methyllycaconitine, implicating α4β2*, but not α7, nAChRs. Thus activation of MAPK in functionally distinct forebrain circuits--thalamocortical, local intracortical, and long-range intracortical--underlies nicotinic neuromodulation of A1." @default.
• W2007067260 created "2016-06-24" @default.
• W2007067260 creator A5010578262 @default.
• W2007067260 creator A5075276271 @default.
• W2007067260 date "2012-05-15" @default.
• W2007067260 modified "2023-10-18" @default.
• W2007067260 title "Nicotinic neuromodulation in auditory cortex requires MAPK activation in thalamocortical and intracortical circuits" @default.
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• W2007067260 doi "https://doi.org/10.1152/jn.01129.2011" @default.
• W2007067260 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3362282" @default.
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