Heightened Nicotinic Regulation of Auditory Cortex during Adolescence

Department of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California 92697, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2011; 31(40):14367-77. DOI: 10.1523/JNEUROSCI.1705-11.2011
Source: PubMed


Adolescent smoking is associated with auditory-cognitive deficits and structural alterations to auditory thalamocortical systems, suggesting that higher auditory function is vulnerable to nicotine exposure during adolescence. Although nicotinic acetylcholine receptors (nAChRs) regulate thalamocortical processing in adults, it is not known whether they regulate processing at earlier ages since their expression pattern changes throughout postnatal development. Here we investigate nicotinic regulation of tone-evoked current source density (CSD) profiles in mouse primary auditory cortex from just after hearing onset until adulthood. At the youngest ages, systemic nicotine did not affect CSD profiles. However, beginning in early adolescence nicotine enhanced characteristic frequency (CF)-evoked responses in layers 2-4 by enhancing thalamocortical, early intracortical, and late intracortical response components. Nicotinic responsiveness developed rapidly and peaked over the course of adolescence, then declined thereafter. Generally, responsiveness in females developed more quickly, peaked earlier, and declined more abruptly and fully than in males. In contrast to the enhancement of CF-evoked responses, nicotine suppressed shorter-latency intracortical responses to spectrally distant (non-CF) stimuli while enhancing longer-latency responses. Intracortical infusion of nAChR antagonists showed that enhancement of CF-evoked intracortical processing involves α4β2*, but not α7, nAChRs, whereas both receptor subtypes regulate non-CF-evoked late intracortical responses. Notably, antagonist effects in females implied regulation by endogenous acetylcholine. Thus, nicotinic regulation of cortical processing varies with age and sex, with peak effects during adolescence that may contribute to the vulnerability of adolescents to smoking.

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    • "current sink without affecting modulation of peak current sinks in layer 2/3 (Intskirveli & Metherate, 2012). Conversely, intracortical drug treatments, such as intracortical silencing using the GABA-A receptor agonist muscimol, can affect peak current sinks in layers 2–4 without affecting the first 3–5 ms of the layer 4 sink (Happel et al., 2010; Intskirveli & Metherate, 2012; Kaur et al., 2004; Kawai et al., 2011 "
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    ABSTRACT: Auditory-cued behavioral training can alter neural circuits in primary auditory cortex (A1), but the mechanisms and consequences of experience-dependent cortical plasticity are not fully understood. To address this issue, we trained adult rats to detect a 5 kHz target in order to receive a food reward. After 14 days training we identified three locations within A1: i) the region representing the characteristic frequency (CF) 5 kHz, ii) a nearby region with CF ∼10 kHz, and iii) a more distant region with CF ∼20 kHz. In order to compare functional connectivity in A1 near to, vs. far from, the representation of the target frequency, we placed a 16-channel multiprobe in middle- (∼10 kHz) and high- (∼20 kHz) CF regions and obtained current-source density (CSD) profiles evoked by a range of tone stimuli (CF ± 1-3 octaves in quarter-octave steps). Our aim was to construct "CSD receptive fields" (CSD RFs) in order to determine the laminar and spectral profile of tone-evoked current sinks, and infer changes to thalamocortical and intracortical inputs. Behavioral training altered CSD RFs at the 10 kHz, but not 20 kHz, site relative to CSD RFs in untrained control animals. At the 10 kHz site, current sinks evoked by the target frequency were enhanced in layer 2/3, but the initial current sink in layer 4 was not altered. The results imply training-induced plasticity along intracortical pathways connecting the target representation with nearby cortical regions. Finally, we related behavioral performance (sensitivity index, d') to CSD responses in individual animals, and found a significant correlation between the development of d' over training and the amplitude of the target-evoked current sink in layer 2/3. The results suggest that plasticity along intracortical pathways is important for auditory learning.
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    • "Still other cases exhibited a mix of effects (Figure 5B shows enhancement of shorter latency nonCF-evoked response and lesser effects at longer latencies). Nevertheless, in all cases nicotine's effects on nonCF responses contrasted with its enhancement of CF-evoked responses, and overall suppression of nonCF-evoked profiles emerged in group data, as reported (Kawai et al., 2011; Intskirveli and Metherate, 2012), although the group data mask the diversity of effects. "
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    • "The present results showing differential effects of nicotine on CF-versus nonCF-evoked responses— e.g., enhancement versus either suppression or no effect , respectively—further support the notion of distinct underlying circuits (see also similar findings from Kawai et al. 2011). Blockade of nicotinic suppression by MEK inhibition implies regulation of long-distance pathways. "
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