Heightened Nicotinic Regulation of Auditory Cortex during Adolescence

ArticleinThe Journal of Neuroscience : The Official Journal of the Society for Neuroscience 31(40):14367-77 · October 2011with11 Reads
DOI: 10.1523/JNEUROSCI.1705-11.2011 · Source: PubMed
Abstract
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.
    • "a7-nAChRs and D2-like DA receptors are also partially targeted to the same pyramidal and fast-spiking interneuron populations [215], indicating that these neurons receive significant nicotinic modulation even after prolonged nicotine exposure. On the short-term, nicotine affects PFC-dependent behavior such as impulsivity and performance in visuospatial attention tasks, but nicotine exposure during adolescence is also associated with longer-lasting changes in behavior ranging from nicotine sensitivity, attention to impulsivity [123,193194195. Biological processes underlying these behavioral effects include increased gene expression of a5, a6 and b2 subunits of nAChRs, altered structure of subcortical white matter, and a long-lasting reduction of short-term plasticity on glutamatergic inputs to PFC layer 5 output pyramidal neurons [193,196197198199. Studies reporting increased cigarette smoking in humans with a polymorphism in the gene for a5-nAChR subunit as well as increased expression of a5-subunits after adolescent nicotine exposure may provide a link with increased resilience to nicotine-induced desensitization of a5-containing nAChRs [193,200]. "
    [Show abstract] [Hide abstract] ABSTRACT: Nicotine addiction is highly prevalent in current society, and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are found in most brain regions, many studies on addiction have focused on the mesolimbic system and its reported behavioral correlates such as reward processing and reinforcement learning. Profound modulatory cholinergic input from the pedunculopontine and laterodorsal tegmentum to dopaminergic midbrain nuclei as well as local cholinergic interneuron projections to dopamine neuron axons in the striatum may play a major role in the effects of nicotine. Moreover, an indirect mesocorticolimbic feedback loop involving the medial prefrontal cortex may be involved in behavioral characteristics of nicotine addiction. Therefore, this review will highlight current understanding of the effects of nicotine on the function of mesolimbic and mesocortical dopamine projections in the mesocorticolimbic circuit. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jul 2015
    • "Although we did not perform a detailed quantitative analysis of nAChR distribution in SS and Fr2, our qualitative comparison broadly confirms previous results obtained in rodents' SS (Bravo and Karten, 1992; Hill et al., 1993; Nakayama et al., 1995; Schr€ oder, 1992; Whiteaker et al., 2006). More recent observations aimed to better discriminate the laminar distribution and function of nAChRs in different neocortical regions of mice (Brown et al., 2012; Kawai et al., 2011; Poorthuis et al., 2012). However, the overall picture is still uncertain, because the anatomical studies focused on SS, whereas the electrophysiological approaches were mainly directed toward the prefrontal regions. "
    [Show abstract] [Hide abstract] ABSTRACT: We studied how nicotinic acetylcholine receptors (nAChRs) regulate glutamate release in the secondary motor area (Fr2) of the dorsomedial murine prefrontal cortex, in the presence of steady agonist levels. Fr2 mediates response to behavioral situations that require immediate attention and is a candidate for generating seizures in the frontal epilepsies caused by mutant nAChRs. Morphological analysis showed a peculiar chemoarchitecture and laminar distribution of pyramidal cells and interneurons. Tonic application of 5 μM nicotine on layer V pyramidal neurons strongly increased the frequency of spontaneous glutamatergic excitatory postsynaptic currents (EPSCs). The effect was inhibited by 1 μM dihydro-β-erythroidine (DHβE, which blocks α4-containing nAChRs), but not by 10 nM methyllicaconitine (MLA, which blocks α7-containing receptors). EPSCs were also stimulated by 5-iodo-3-[2(S)-azetidinylmethoxy]pyridine (5IA85380), selective for β2-containing receptors, in a DHβE-sensitive way. We next studied the association of α4 with different populations of glutamatergic terminals, by using as markers the vesicular glutamate transporter type 1 (VGLUT1) for cortico-cortical synapses, and type 2 (VGLUT2) for thalamo-cortical projecting fibers. Immunoblots showed higher expression of α4 in Fr2, as compared to the somatosensory (SS) cortex. Immunofluorescence showed intense VGLUT1 staining throughout the cortical layers, whereas VGLUT2 immunoreactivity displayed a more distinct laminar distribution. In layer V, co-localization of α4 nAChR subunit with both VGLUT1 and VGLUT2 was considerably stronger in Fr2 than in SS cortex. Thus, in Fr2, α4β2 nAChRs are expressed in both intrinsic and extrinsic glutamatergic terminals and give a major contribution to control glutamate release in layer V, in the presence of tonic agonist levels. Synapse, 2013. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Jun 2013
    • "Specifically, pharmacological manipulations of the thalamus can reduce the amplitude of the layer 4 current sink (Kawai et al., 2007), or block modulation of the first 3–5 ms of the layer 4 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). These results support the interpretation of CF-evoked CSD profiles used here: the first 3 ms of the layer 4 current sink largely reflects monosynaptic thalamocortical transmission, whereas longer-latency responses in layers 2–4—in particular, the peak current sink in layer 2/3—largely reflect intracortical contributions. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Jan 2013
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