- Open Access
M1 muscarinic receptor for the development of auditory cortical function
© Shideler and Yan; licensee BioMed Central Ltd. 2010
Received: 27 August 2010
Accepted: 22 October 2010
Published: 22 October 2010
The sensory cortex is subject to continuous remodelling during early development and throughout adulthood. This process is important for establishing normal brain function and is dependent on cholinergic modulation via muscarinic receptors. Five muscarinic receptor genes encode five unique receptor subtypes (M1-5). The distributions and functions of each subtype vary in central and peripheral systems. In the brain, the M1 receptor is most abundant in the cerebral cortex, where its immunoreactivity peaks transiently during early development. This likely signifies the importance of M1 receptor in the development and maintenance of normal cortical function. Several lines of study have outlined the roles of M1 receptors in the development and plasticity of the auditory cortex. For example, M1-knockout reduces experience-dependent plasticity and disrupts tonotopic mapping in the adult mouse auditory cortex. Further evidence demonstrates a role for M1 in neurite outgrowth and hence determining the structure of cortical neurons. The disruption of tonotopic maps in M1-knockout mice may be linked to alterations in thalamocortical connectivity, because the targets of thalamocortical afferents (layer IV cortical neurons) appear less mature in M1 knockouts. Herein we review the literature to date concerning M1 receptors in the auditory cortex and consider some future directions that will contribute to our understanding.
Interestingly, some of the tonotopic-like organization of the auditory system is present before the sensory input of sound is available [9–11]. For example, at E15.5 the projections of spiral ganglion cells onto the cochlear nucleus are tonotopically correct, i.e., spiral ganglion neurons that will innervate the cochlear base or apex, already innervate the dorso-medial or ventro-lateral cochlear nucleus, respectively . Within the cortex, tonotopic-like maps depend on spontaneous activity initially, before opening of the ear canal, and then become mature after a so-called 'critical period' of early development . Mature maps are generally composed of neurons in orderly array, tuned to various frequencies appropriate to the hearing range of a given species, and they have sharp frequency-tuning curves. The generation of mature maps is highly dependent on early experience of the acoustic environment .
Cholinergic neurons within the nucleus basalis and the septal diagonal band complex provide the major source of cholinergic innervation of the cerebral cortex and hippocampus and play key roles in memory  and attention . A role for acetylcholine (ACh) as a classical neuromodulator in the central nervous system - including the cerebral cortex - is supported by a wealth of published data. Despite the abundance of articles exploring the possible roles of cholinergic input, many mechanisms underlying cholinergic modulation are still not well understood. It is intriguing to consider that early neonatal ablation of cholinergic projections from basal forebrain to cortex results in considerable structural abnormalities within the cortex, such as: smaller soma size and shorter apical and basal dendritic branches of pyramidal neurons; unclear boundaries between supragranular layers; abnormal pattern-formation in layer IV; and irregular intracortical connectivity and altered distribution of thalamocortical projections in the neocortex [17–19]. The specific actions by which ACh can mediate these morphological changes is unclear. The authors of the aforementioned ablation studies hypothesized, and the evidence presented later in this review suggests, that muscarinic acetylcholine receptor (mAChR) subtype 1 (M1) is a key player in determining normal cortical development and function. This review will focus specifically on M1 and the auditory cortex, as significant recent work has been conducted in the auditory system.
Acetylcholine Receptors and Function in Brain.
Facilitates thalamocortical transmission
Unclear roles in plasticity and development
Promotes Cell Survival
Promotes Cell Survival
Promotes Cell Survival
Impact auditory plasticity
Impact auditory plasticity
Impact auditory plasticity
Impact auditory plasticity
Perinatally, both nAChRs and mAChRs are present in the mammalian cerebral cortex . However, during the course of cortical development the expression (mRNA) levels of most nAChRs are constant, whereas those of mAChRs vary, having peak periods within the first several weeks of postnatal life that correspond with times of morphogenesis and synaptogenesis . These patterns suggest that the presence of mAChRs could play an important role in development and maturation in the auditory cortex. On the other hand, nAChRs also undoubtedly play some role in normal cortical developmental. For example, the cortical pyramidal cells of nAChR-β2 subunit knockout mice had shorter dendritic arbours and lower spine densities than those of wild-type mice . Furthermore, within the auditory system, activation of cortical nAChRs was found to enhance cognitive function [34–36]; rats that performed well in an auditory-cued active avoidance task also responded to nicotine administration with enhanced response to stimuli, as long as the tone used was close to the conditioning tone. Interestingly, in addition, nicotine administration not only enhanced the response to a closely matched tone, but it also reduced responses to spectrally distant stimuli. Because these effects were observed only in the population of rats that performed well in the initial trials, perhaps the role of nAChRs was to exert some refining effect upon plasticity . In general, studying nAChR can be complex, as many combinations of different nAChR subunits can form homo- and heteromeric pentameric channels, producing a large variety of channels having varying kinetics and pharmacology. The complexity of roles of nAChR receptors in cortical development warrants a dedicated discussion, which is outside of the scope of this review.
Although the types and functional mechanisms of mAChRs are considerably less complex than those of nAChRs. a comprehensive understanding still poses serious challenges. Many organs express more than one mAChR subtype [20, 37–39]. In the adult brain, all mAChR subtypes are present, and they are expressed in regionally specific patterns. The distributions and concentrations of mAChR subtypes are commonly determined by localizing mAChR mRNA with in situ hybridization, by identifying mAChR protein immunohistochemically, and by measuring mRNA or localizing muscarinic ligand-binding. Early experiments indicated that M1, M2 and M4 mRNA and protein were the most abundant mAChRs in the brain [38, 39], and that M1 was the predominant mAChR in the cerebral cortex [32, 38]. It is noteworthy that the expression of M1 protein in the cerebral cortex shows a specific pattern and that the patterns of immunoreactivity of M1 and M2 in the different cortical layers seem to be strongly complementary throughout development . In mice, immunoreactive M1 protein can be detected in the brain as early as P5; and by P14, M1-immunoreactivity is most apparent in layer IV, whereas M2-immunoreactivity is strongest in layers II/III and V . These results suggest that M1 and M2 could be important to the differentiation of unique phenotypes of cortical neurons during early development .
A plethora of intrinsic and extrinsic cues guide cell migration and other events in the development of the cerebral cortex. Some key players in cortical formation include the proteins reelin, which controls migration and positioning of cortical neurons[40, 41]; cyclin-dependent kinase 5 (Cdk5), which is part of the reelin signaling cascade and also aids in appropriate migration[41, 42]; and the Slit family of proteins, acting through Robo receptors, which may guide cortical interneurons into the cortex and play roles in dendritic growth and axonal pathfinding [43, 44]. Additionally, various microtubule proteins , centrosome proteins  and neurotrophic factors  also support normal development, maturation and function. Data suggest that cholinergic neuronal activity, involving specifically M1 mAChR, regulates the expression of neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) [46–48]. Other links between mAChRs and important regulators of development seem likely but have not yet been established. Given the paucity of current literature, the role(s) of mAChRs in developmental programming - especially within the auditory system - would appear to be an area ripe for further investigation.
In addition to the data discussed above, the results of a few experiments have more directly demonstrated a role of mAChRs and M1 in determining the structure of neurons. Transfection of several cell lines with cDNA for rat choline acetyltransferase (ChAT) stimulated neurite outgrowth and produced a more differentiated phenotype . Further investigation demonstrated that mAChRs were present on these cells, leading to the hypothesis that they were essential to the neurite outgrowth , and the activation of mAChRs was shown to be sufficient to initiate neurite outgrowth and the induction of synapsin 1 [49, 50]. Synapsin 1, a synaptic vesicle-associated protein that is expressed during synaptogenesis, is involved classically in vesicle release; but it also promotes the elongation of neurites and mediates the formation of reciprocal contacts between neurites and the functional maturation of synapses [51, 52]. Activation of mAChR by pretreatment with oxotremorine-M, a selective mAChR agonist, has also been shown to promote cell survival [27, 53]; this could be important during neuronal development. Furthermore, M1 is involved in signaling pathways that are active during synaptogenesis, such as activation of the gamma (γ) and epsilon (ε) isoforms of protein kinase C (PKC) [26, 31] and the mitogen-activated protein kinase (MAPK) pathway [31, 54]. In vitro experiments have demonstrated that specifically M1 activation can signal through PKCε, resulting in robust outgrowth of neurites from pyramidal cells . These in vitro studies suggest an interpretation that M1 contributes to neurite outgrowth in vivo as well; the length of dendrites of layer 4 multipolar granular cells in the auditory cortex was significantly shorter in M1 knockout mice than in wild-type controls . Evidence from ablation of cholinergic inputs also suggests that M1 signalling is essential for the morphological maturation of the cerebral cortex . While direct or indirect signalling events that occur after M1 activation may help to regulate the morphological parameters of cortical neurons, specifically, the length of their neurites, certainly many other factors could contribute to the regulation of neurite outgrowth. Moreover, in the auditory cortex, the dendrites of layer 4 neurons were significantly shorter in M1 knockout mice, whereas those of layer 5 neurons were not significantly different from wild-type controls . Very few morphological findings have been reported in investigations of mAChR knockout mice. Whether or not stunted neurite outgrowth is observed in other cortical areas is currently unknown. It is possible that M1 plays some previously unexplored role in layer 4 of the auditory cortex; conversely, the shortening of dendrites in the absence of M1signalling in vivo may be a more general phenomenon than has been documented so far. This observation may be indicative of an alteration in either the thalamic innervation of the cortex, or the formation of synapses from thalamocortical afferents onto cortical neurons (usually in layer 4), in mice lacking M1 receptors .
A regulatory role for mAChRs, especially M1, has also been confirmed in development and plasticity in other areas of sensory cortex. In the visual system, intracortical infusion of pirenzepine, a moderately selective M1-receptor antagonist, significantly reduces ocular dominance plasticity due to postnatal monocular deprivation in cats . In the somatosensory system, it has been demonstrated the Ca2+-currents generated by mAChR-activation help to synchronize neuronal responses . Synchronous firing, early in the development of networks such as the thalamocortical connections, is believed to promote the normal development of these cortical structures . Lastly, in studies investigating learning-induced auditory plasticity, cortical application of the mAChR antagonists atropine or scopolamine significantly decreased the frequency-specific plasticity of the auditory cortex when evoked by auditory fear-conditioning [57–59] or basal forebrain stimulation paired with a sound [30, 60–62].
More specifically, our laboratory has previously demonstrated that the auditory systems of 4-week-old M1 knockout mice are physiologically abnormal in several ways. The reported deficits include, firstly, a reduction in number of cortical neurons tuned to 20 kHz and above; this may reflect some form of altered maturation, because after ear-opening, the best frequency of neurons tends to shift toward higher frequencies . It was also reported that, in M1 knockout mice, greater numbers of neurons in the auditory cortex had multi-peaked frequency-tuning curves ; in contrast, fewer than half of the neurons in the primary auditory cortex and anterior auditory cortex of wild type mice had multi-peaked best frequencies . Although the exact cause of more multi-peaked tuning curves is unknown, it is reasonable to suggest that an abnormality in thalamocortical input is responsible. This proposed abnormality could be due to a minor misguiding of thalamocortical fibres, or perhaps a network-mediated effect in which there is a lack of inhibition of a response to other tones . Also likely related to this is the observation that the tonotopic maps in auditory cortex of M1 knockout mice are disrupted. Typically, auditory tonotopy is characterized by a systematic organization of neural responses, in which neurons in the dorsal portion of the auditory cortex are tuned to high frequencies, whereas those in rostral and caudal portions are tuned to lower frequencies . In M1 knockout mice, however, this systematic dorsal to rostro-caudal pattern was not clear, and it was difficult to delineate the subdivisions of the auditory cortex on the basis of tonotopic organization . Both the lack of cells with a best frequency over 20 kHz, and the poor organization of the tonotopic map of the primary and anterior auditory cortex, suggest that a lack of M1 may stunt functional maturation of the cortex and interfere with developmental plasticity . Moreover, it has been demonstrated that ACh release within the auditory cortex activates particularly the M1 receptor, thereby enhancing postsynaptic activity and glutamate-mediated membrane potentiation via AMPA- (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and NMDA- (N-methyl-D-aspartic acid) type ionotropic glutamate receptors [64–66]. It has been shown that blockade of AMPA- and NMDA-receptors by both APV ((2R)-amino-5-phosphonopentanoate) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) reduces the length and density of postsynaptic dendrites . It would be interesting to investigate whether antagonizing AMPA- and NMDA-receptors, via long-term continuous neonatal microinjection to the auditory cortex, would produce the same tonotopic disorganization and morphological findings as M1 knockout. Conversely, an AMPA- or NMDA-receptor-mediated attempt at rescuing the M1 knockout could also be informative for determining a mechanism by which M1 acts in the auditory cortex. The result of deletion the m1 gene seems to be an auditory cortex that is both functionally and structurally less mature than wild-type, and in which thalamocortical connectivity has been altered.
In regards to plastic changes, frequency-specific plasticity was smaller in magnitude, and shifted less towards the presented tone and for a shorter duration, in M1-deficient mice . This suggests that M1 -receptors are critical for input-specific plasticity in the auditory cortex and may influence learning-induced or experience-dependent cortical plasticity . Behavioural studies demonstrate that M1 mutants do well in matching-to-sample problems, but are deficient in solving non-matching-to-sample working memory tasks . On the other hand, some authors have reported that M1 receptors play an important role in the regulation of locomotor activity and have described the mutants as having a hyperactivity phenotype, suggesting that this - rather than any cognitive deficit - may be responsible for their impaired performance in a behavioural test . While increased locomotor activity does nothing to explain the decreased input-specific plasticity in the auditory cortex of M1 knockout mice; it does serve to demonstrate the complexity of the issue at hand. M1 does seem to impact some part of learning, memory and plasticity; however, the mechanism or mechanisms underlying its influence remain elusive. Investigation of conditional knockout mice could be a useful technique, not only for the elimination of potentially extraneous effects in other organ systems (complicating the data), but also for pinpointing important windows of time during which M1 mediates critical developmental processes. Also, aiming conditional knockout techniques at thalamocortical neurons or hippocampal neurons, for example, could clarify whether M1 acts differently in different cell populations and help to delineate its role in learning and memory.
Finally, it would seem prudent to discuss pathological conditions in which M1 may be involved. Although mAChRs have been implicated in numerous pathologies, the precise nature of their involvement is frequently controversial. Examples include: schizophrenia [70–74], Alzheimer disease [75–77] and other dementias [77, 78]. Schizophrenia may be an interesting focus for studying the role of M1 in the auditory system, as auditory hallucinations are a hallmark of the disorder . Clinical trials of muscarinic drugs in these disorders have met with mixed success. Psychiatric illnesses that affect children may also be interesting, and the possible roles of M1 in the pathogenesis of (e.g.) autism  and attention-deficiency disorder  are also being investigated. Certainly, as our basic understanding of the roles of these receptors increases, it is likely that our insight into the associated pathologies will increase also.
In summary, a growing body of literature suggests that M1 is important to the normal development and physiology of the auditory cortex. While many questions remain about the precise mechanisms of action in vivo, several in vitro studies highlight specific signaling pathways, involving molecular regulators such as PKC  and NMDA-receptors [64–66]. Although some studies have pointed towards possible mechanisms, most of the available data consist only of correlations that suggest an involvement of M1 in development of auditory cortex and thalamocortical projections but do not demonstrate causal roles. Further investigation of the auditory system of M1 knockout mice may lead to a better understanding of the role of a single subtype of mAChR, uncomplicated by the limited specificity of muscarinic drugs . However, since M1 is expressed in several organs and may play different roles in the embryo, neonate and adult, investigation of conditional knockouts is likely to be much more useful. The direct role of M1 in thalamocortical connectivity in the cortex is of particular interest, given the critical importance of thalamic input for sensory processing and auditory perception in the cortex.
We would like to acknowledge the continued callboration and support of Drs Richard Dyck and William Stell. The research of the authors and those acknowledged was funded by the Natural Sciences and Engineering Research Council of Canada. Drs. Yan and Dyck also recieve funding from the Canadian Institutes of Health Research.
- Molnar Z, Hoerder-Suabedissen A, Wang WZ, DeProto J, Davies K, Lee S, Jacobs EC, Campagnoni AT, Paulsen O, Pinon MC, Cheung AF: Genes involved in the formation of the earliest cortical circuits. Novartis Found Symp. 2007, 288: 212-224. full_text. discussion 224-219, 276-281View ArticlePubMedGoogle Scholar
- Chen P, Segil N: p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development. 1999, 126: 1581-1590.PubMedGoogle Scholar
- Woods C, Montcouquiol M, Kelley MW: Math1 regulates development of the sensory epithelium in the mammalian cochlea. Nat Neurosci. 2004, 7: 1310-1318. 10.1038/nn1349.View ArticlePubMedGoogle Scholar
- New York Plenum, Jones E: The thalamus. 1985, New York PlenumView ArticleGoogle Scholar
- Gurung B, Fritzsch B: Time course of embryonic midbrain and thalamic auditory connection development in mice as revealed by carbocyanine dye tracing. J Comp Neurol. 2004, 479: 309-327. 10.1002/cne.20328.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhao C, Kao JP, Kanold PO: Functional excitatory microcircuits in neonatal cortex connect thalamus and layer 4. J Neurosci. 2009, 29: 15479-15488. 10.1523/JNEUROSCI.4471-09.2009.PubMed CentralView ArticlePubMedGoogle Scholar
- Hohmann CF, Berger-Sweeney J: Cholinergic regulation of cortical development and plasticity. New twists to an old story. Perspect Dev Neurobiol. 1998, 5: 401-425.PubMedGoogle Scholar
- Pujol R, Lavigne-Rebillard M, Lenoir M: Development of sensory and neural structures in the mammalian cochlea. Development of the auditory system. Edited by: E R, A P, R F. 1997, Berlin: Spinger, 146-192.Google Scholar
- Hoffpauir BK, Marrs GS, Mathers PH, Spirou GA: Does the brain connect before the periphery can direct? A comparison of three sensory systems in mice. Brain Res. 2009, 1277: 115-129. 10.1016/j.brainres.2009.02.050.PubMed CentralView ArticlePubMedGoogle Scholar
- Hartmann R, Shepherd RK, Heid S, Klinke R: Response of the primary auditory cortex to electrical stimulation of the auditory nerve in the congenitally deaf white cat. Hear Res. 1997, 112: 115-133. 10.1016/S0378-5955(97)00114-7.View ArticlePubMedGoogle Scholar
- Shepherd RK, Hartmann R, Heid S, Hardie N, Klinke R: The central auditory system and auditory deprivation: experience with cochlear implants in the congenitally deaf. Acta Otolaryngol Suppl. 1997, 532: 28-33. 10.3109/00016489709126141.View ArticlePubMedGoogle Scholar
- Pierce ET: Histogenesis of the dorsal and ventral cochlear nuclei in the mouse. An autoradiographic study. J Comp Neurol. 1967, 131: 27-54. 10.1002/cne.901310104.View ArticlePubMedGoogle Scholar
- de Villers-Sidani E, Chang EF, Bao S, Merzenich MM: Critical period window for spectral tuning defined in the primary auditory cortex (A1) in the rat. J Neurosci. 2007, 27: 180-189. 10.1523/JNEUROSCI.3227-06.2007.View ArticlePubMedGoogle Scholar
- Zhang LI, Bao S, Merzenich MM: Persistent and specific influences of early acoustic environments on primary auditory cortex. Nat Neurosci. 2001, 4: 1123-1130. 10.1038/nn745.View ArticlePubMedGoogle Scholar
- Hasselmo ME, Anderson BP, Bower JM: Cholinergic modulation of cortical associative memory function. J Neurophysiol. 1992, 67: 1230-1246.PubMedGoogle Scholar
- Bucci DJ, Holland PC, Gallagher M: Removal of cholinergic input to rat posterior parietal cortex disrupts incremental processing of conditioned stimuli. J Neurosci. 1998, 18: 8038-8046.PubMedGoogle Scholar
- Hohmann CF, Brooks AR, Coyle JT: Neonatal lesions of the basal forebrain cholinergic neurons result in abnormal cortical development. Brain research. 1988, 470: 253-264.View ArticlePubMedGoogle Scholar
- Hohmann CF, Coyle JT: Long-term effects of basal forebrain lesions on cholinergic, noradrenergic and serotonergic markers in mouse neocortex. Brain research bulletin. 1988, 21: 13-20. 10.1016/0361-9230(88)90113-X.View ArticlePubMedGoogle Scholar
- Hohmann CF, Ebner FF: Basal forebrain lesions facilitate adult host fiber ingrowth into neocortical transplants. Brain research. 1988, 448: 53-66. 10.1016/0006-8993(88)91101-8.View ArticlePubMedGoogle Scholar
- Lucas-Meunier E, Fossier P, Baux G, Amar M: Cholinergic modulation of the cortical neuronal network. Pflugers Arch. 2003, 446: 17-29.View ArticlePubMedGoogle Scholar
- Mulle C, Choquet D, Korn H, Changeux JP: Calcium influx through nicotinic receptor in rat central neurons: its relevance to cellular regulation. Neuron. 1992, 8: 135-143. 10.1016/0896-6273(92)90115-T.View ArticlePubMedGoogle Scholar
- Seguela P, Wadiche J, Dineley-Miller K, Dani JA, Patrick JW: Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium. J Neurosci. 1993, 13: 596-604.PubMedGoogle Scholar
- Wess J: Molecular biology of muscarinic acetylcholine receptors. Critical reviews in neurobiology. 1996, 10: 69-99.View ArticlePubMedGoogle Scholar
- Caulfield MP, Birdsall NJ: International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacological reviews. 1998, 50: 279-290.PubMedGoogle Scholar
- Clarke PB: Nicotinic modulation of thalamocortical neurotransmission. Prog Brain Res. 2004, 145: 253-260. full_text.View ArticlePubMedGoogle Scholar
- VanDeMark KL, Guizzetti M, Giordano G, Costa LG: The activation of M1 muscarinic receptor signaling induces neuronal differentiation in pyramidal hippocampal neurons. J Pharmacol Exp Ther. 2009, 329: 532-542. 10.1124/jpet.108.150128.PubMed CentralView ArticlePubMedGoogle Scholar
- Tobin AB, Budd DC: The anti-apoptotic response of the Gq/11-coupled muscarinic receptor family. Biochem Soc Trans. 2003, 31: 1182-1185. 10.1042/BST0311182.View ArticlePubMedGoogle Scholar
- Zhang Y, Dyck RH, Hamilton SE, Nathanson NM, Yan J: Disrupted tonotopy of the auditory cortex in mice lacking M1 muscarinic acetylcholine receptor. Hear Res. 2005, 201: 145-155. 10.1016/j.heares.2004.10.003.View ArticlePubMedGoogle Scholar
- Zhang Y, Hamilton SE, Nathanson NM, Yan J: Decreased input-specific plasticity of the auditory cortex in mice lacking M1 muscarinic acetylcholine receptors. Cereb Cortex. 2006, 16: 1258-1265. 10.1093/cercor/bhj067.View ArticlePubMedGoogle Scholar
- Ji W, Suga N: Development of reorganization of the auditory cortex caused by fear conditioning: effect of atropine. J Neurophysiol. 2003, 90: 1904-1909. 10.1152/jn.00363.2003.View ArticlePubMedGoogle Scholar
- Hohmann CF: A morphogenetic role for acetylcholine in mouse cerebral neocortex. Neurosci Biobehav Rev. 2003, 27: 351-363. 10.1016/S0149-7634(03)00066-6.View ArticlePubMedGoogle Scholar
- Hohmann CF, Potter ED, Levey AI: Development of muscarinic receptor subtypes in the forebrain of the mouse. J Comp Neurol. 1995, 358: 88-101. 10.1002/cne.903580106.View ArticlePubMedGoogle Scholar
- Ballesteros-Yanez I, Benavides-Piccione R, Bourgeois JP, Changeux JP, DeFelipe J: Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors. Proc Natl Acad Sci USA. 2010, 107: 11567-11572. 10.1073/pnas.1006269107.PubMed CentralView ArticlePubMedGoogle Scholar
- Liang K, Poytress BS, Chen Y, Leslie FM, Weinberger NM, Metherate R: Neonatal nicotine exposure impairs nicotinic enhancement of central auditory processing and auditory learning in adult rats. Eur J Neurosci. 2006, 24: 857-866. 10.1111/j.1460-9568.2006.04945.x.View ArticlePubMedGoogle Scholar
- Domino EF, Kishimoto T: Tobacco smoking increases gating of irrelevant and enhances attention to relevant tones. Nicotine Tob Res. 2002, 4: 71-78. 10.1080/14622200110098400.View ArticlePubMedGoogle Scholar
- Liang K, Poytress BS, Weinberger NM, Metherate R: Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning. Neurobiol Learn Mem. 2008, 90: 138-146. 10.1016/j.nlm.2008.02.006.PubMed CentralView ArticlePubMedGoogle Scholar
- Dorje F, Levey AI, Brann MR: Immunological detection of muscarinic receptor subtype proteins (m1-m5) in rabbit peripheral tissues. Molecular pharmacology. 1991, 40: 459-462.PubMedGoogle Scholar
- Levey AI: Immunological localization of m1-m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci. 1993, 52: 441-448. 10.1016/0024-3205(93)90300-R.View ArticlePubMedGoogle Scholar
- Levey AI, Kitt CA, Simonds WF, Price DL, Brann MR: Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. J Neurosci. 1991, 11: 3218-3226.PubMedGoogle Scholar
- Forster E, Bock HH, Herz J, Chai X, Frotscher M, Zhao S: Emerging topics in Reelin function. Eur J Neurosci. 2010, 31: 1511-1518.PubMed CentralPubMedGoogle Scholar
- Cooper JA: A mechanism for inside-out lamination in the neocortex. Trends Neurosci. 2008, 31: 113-119. 10.1016/j.tins.2007.12.003.View ArticlePubMedGoogle Scholar
- Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K: Modulation of Reelin signaling by Cyclin-dependent kinase 5. Brain Res. 2007, 1140: 84-95. 10.1016/j.brainres.2006.01.121.View ArticlePubMedGoogle Scholar
- Andrews WD, Barber M, Parnavelas JG: Slit-Robo interactions during cortical development. J Anat. 2007, 211: 188-198. 10.1111/j.1469-7580.2007.00750.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Whitford KL, Marillat V, Stein E, Goodman CS, Tessier-Lavigne M, Chedotal A, Ghosh A: Regulation of cortical dendrite development by Slit-Robo interactions. Neuron. 2002, 33: 47-61. 10.1016/S0896-6273(01)00566-9.View ArticlePubMedGoogle Scholar
- Reichardt LF: Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006, 361: 1545-1564. 10.1098/rstb.2006.1894.PubMed CentralView ArticlePubMedGoogle Scholar
- da Penha Berzaghi M, Cooper J, Castren E, Zafra F, Sofroniew M, Thoenen H, Lindholm D: Cholinergic regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) but not neurotrophin-3 (NT-3) mRNA levels in the developing rat hippocampus. J Neurosci. 1993, 13: 3818-3826.PubMedGoogle Scholar
- von der Kammer H, Demiralay C, Andresen B, Albrecht C, Mayhaus M, Nitsch RM: Regulation of gene expression by muscarinic acetylcholine receptors. Biochem Soc Symp. 2001, 131-140.Google Scholar
- Betancourt AM, Burgess SC, Carr RL: Effect of developmental exposure to chlorpyrifos on the expression of neurotrophin growth factors and cell-specific markers in neonatal rat brain. Toxicol Sci. 2006, 92: 500-506. 10.1093/toxsci/kfl004.View ArticlePubMedGoogle Scholar
- Bignami F, Bevilacqua P, Biagioni S, De Jaco A, Casamenti F, Felsani A, Augusti-Tocco G: Cellular acetylcholine content and neuronal differentiation. J Neurochem. 1997, 69: 1374-1381. 10.1046/j.1471-4159.1997.69041374.x.View ArticlePubMedGoogle Scholar
- De Jaco A, Ajmone-Cat MA, Baldelli P, Carbone E, Augusti-Tocco G, Biagioni S: Modulation of acetylcholinesterase and voltage-gated Na(+) channels in choline acetyltransferase-transfected neuroblastoma clones. J Neurochem. 2000, 75: 1123-1131. 10.1046/j.1471-4159.2000.0751123.x.View ArticlePubMedGoogle Scholar
- Bogen IL, Jensen V, Hvalby O, Walaas SI: Synapsin-dependent development of glutamatergic synaptic vesicles and presynaptic plasticity in postnatal mouse brain. Neuroscience. 2009, 158 (1): 231-41. 10.1016/j.neuroscience.2008.05.055.View ArticlePubMedGoogle Scholar
- Chin LS, Li L, Ferreira A, Kosik KS, Greengard P: Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice. Proceedings of the National Academy of Sciences of the United States of America. 1995, 92: 9230-9234. 10.1073/pnas.92.20.9230.PubMed CentralView ArticlePubMedGoogle Scholar
- De Sarno P, Shestopal SA, King TD, Zmijewska A, Song L, Jope RS: Muscarinic receptor activation protects cells from apoptotic effects of DNA damage, oxidative stress, and mitochondrial inhibition. J Biol Chem. 2003, 278: 11086-11093. 10.1074/jbc.M212157200.PubMed CentralView ArticlePubMedGoogle Scholar
- Hamilton SE, Nathanson NM: The M1 receptor is required for muscarinic activation of mitogen-activated protein (MAP) kinase in murine cerebral cortical neurons. J Biol Chem. 2001, 276: 15850-15853. 10.1074/jbc.M011563200.View ArticlePubMedGoogle Scholar
- Gu Q: Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity. Neuroscience. 2002, 111: 815-835. 10.1016/S0306-4522(02)00026-X.View ArticlePubMedGoogle Scholar
- Hanganu IL, Okabe A, Lessmann V, Luhmann HJ: Cellular mechanisms of subplate-driven and cholinergic input-dependent network activity in the neonatal rat somatosensory cortex. Cereb Cortex. 2009, 19: 89-105. 10.1093/cercor/bhn061.View ArticlePubMedGoogle Scholar
- Ji W, Suga N: Tone-specific and nonspecific plasticity of inferior colliculus elicited by pseudo-conditioning: role of acetylcholine and auditory and somatosensory cortices. J Neurophysiol. 2009, 102: 941-952. 10.1152/jn.00222.2009.PubMed CentralView ArticlePubMedGoogle Scholar
- Ji W, Suga N, Gao E: Effects of agonists and antagonists of NMDA and ACh receptors on plasticity of bat auditory system elicited by fear conditioning. J Neurophysiol. 2005, 94: 1199-1211. 10.1152/jn.00112.2005.View ArticlePubMedGoogle Scholar
- Feiro O, Gould TJ: The interactive effects of nicotinic and muscarinic cholinergic receptor inhibition on fear conditioning in young and aged C57BL/6 mice. Pharmacol Biochem Behav. 2005, 80: 251-262. 10.1016/j.pbb.2004.11.005.View ArticlePubMedGoogle Scholar
- Bakin JS, Weinberger NM: Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis. Proc Natl Acad Sci USA. 1996, 93: 11219-11224. 10.1073/pnas.93.20.11219.PubMed CentralView ArticlePubMedGoogle Scholar
- Weinberger NM: Physiological memory in primary auditory cortex: characteristics and mechanisms. Neurobiol Learn Mem. 1998, 70: 226-251. 10.1006/nlme.1998.3850.View ArticlePubMedGoogle Scholar
- Weinberger NM: The nucleus basalis and memory codes: auditory cortical plasticity and the induction of specific, associative behavioral memory. Neurobiol Learn Mem. 2003, 80: 268-284. 10.1016/S1074-7427(03)00072-8.View ArticlePubMedGoogle Scholar
- Happel MF, Jeschke M, Ohl FW: Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input. J Neurosci. 2010, 30: 11114-11127. 10.1523/JNEUROSCI.0689-10.2010.View ArticlePubMedGoogle Scholar
- Aramakis VB, Bandrowski AE, Ashe JH: Activation of muscarinic receptors modulates NMDA receptor-mediated responses in auditory cortex. Exp Brain Res. 1997, 113: 484-496. 10.1007/PL00005601.View ArticlePubMedGoogle Scholar
- Aramakis VB, Bandrowski AE, Ashe JH: Role of muscarinic receptors, G-proteins, and intracellular messengers in muscarinic modulation of NMDA receptor-mediated synaptic transmission. Synapse. 1999, 32: 262-275. 10.1002/(SICI)1098-2396(19990615)32:4<262::AID-SYN3>3.0.CO;2-J.View ArticlePubMedGoogle Scholar
- Metherate R, Weinberger NM: Cholinergic modulation of responses to single tones produces tone-specific receptive field alterations in cat auditory cortex. Synapse. 1990, 6: 133-145. 10.1002/syn.890060204.View ArticlePubMedGoogle Scholar
- Rajan I, Cline HT: Glutamate receptor activity is required for normal development of tectal cell dendrites in vivo. J Neurosci. 1998, 18: 7836-7846.PubMedGoogle Scholar
- Anagnostaras SG, Murphy GG, Hamilton SE, Mitchell SL, Rahnama NP, Nathanson NM, Silva AJ: Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat Neurosci. 2003, 6: 51-58. 10.1038/nn992.View ArticlePubMedGoogle Scholar
- Miyakawa T, Yamada M, Duttaroy A, Wess J: Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor. J Neurosci. 2001, 21: 5239-5250.PubMedGoogle Scholar
- Raedler TJ, Bymaster FP, Tandon R, Copolov D, Dean B: Towards a muscarinic hypothesis of schizophrenia. Mol Psychiatry. 2007, 12: 232-246.PubMedGoogle Scholar
- Raedler TJ, Knable MB, Jones DW, Urbina RA, Gorey JG, Lee KS, Egan MF, Coppola R, Weinberger DR: In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry. 2003, 160: 118-127. 10.1176/appi.ajp.160.1.118.View ArticlePubMedGoogle Scholar
- Scarr E, Dean B: Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia?. J Neurochem. 2008, 107: 1188-1195. 10.1111/j.1471-4159.2008.05711.x.View ArticlePubMedGoogle Scholar
- Scarr E, Cowie TF, Kanellakis S, Sundram S, Pantelis C, Dean B: Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia. Mol Psychiatry. 2009, 14: 1017-1023. 10.1038/mp.2008.28.View ArticlePubMedGoogle Scholar
- Deng C, Huang XF: Decreased density of muscarinic receptors in the superior temporal gyrusin schizophrenia. J Neurosci Res. 2005, 81: 883-890. 10.1002/jnr.20600.View ArticlePubMedGoogle Scholar
- Bodick NC, Offen WW, Levey AI, Cutler NR, Gauthier SG, Satlin A, Shannon HE, Tollefson GD, Rasmussen K, Bymaster FP, et al: Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol. 1997, 54: 465-473.View ArticlePubMedGoogle Scholar
- Koch HJ, Haas S, Jurgens T: On the physiological relevance of muscarinic acetylcholine receptors in Alzheimer's disease. Curr Med Chem. 2005, 12: 2915-2921. 10.2174/092986705774454742.View ArticlePubMedGoogle Scholar
- Piggott MA, Owens J, O'Brien J, Colloby S, Fenwick J, Wyper D, Jaros E, Johnson M, Perry RH, Perry EK: Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease. J Chem Neuroanat. 2003, 25: 161-173. 10.1016/S0891-0618(03)00002-4.View ArticlePubMedGoogle Scholar
- Nordberg A, Alafuzoff I, Winblad B: Nicotinic and muscarinic subtypes in the human brain: changes with aging and dementia. J Neurosci Res. 1992, 31: 103-111. 10.1002/jnr.490310115.View ArticlePubMedGoogle Scholar
- Perry EK, Lee ML, Martin-Ruiz CM, Court JA, Volsen SG, Merrit J, Folly E, Iversen PE, Bauman ML, Perry RH, Wenk GL: Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psychiatry. 2001, 158: 1058-1066. 10.1176/appi.ajp.158.7.1058.View ArticlePubMedGoogle Scholar
- Wess J: Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications. Annu Rev Pharmacol Toxicol. 2004, 44: 423-450. 10.1146/annurev.pharmtox.44.101802.121622.View ArticlePubMedGoogle Scholar
- Hohmann CF, Ebner FF: Development of cholinergic markers in mouse forebrain. I. Choline acetyltransferase enzyme activity and acetylcholinesterase histochemistry. Brain Res. 1985, 355: 225-241.View ArticlePubMedGoogle Scholar
- Wall SJ, Yasuda RP, Li M, Ciesla W, Wolfe BB: The ontogeny of m1-m5 muscarinic receptor subtypes in rat forebrain. Brain Res Dev Brain Res. 1992, 66: 181-185. 10.1016/0165-3806(92)90078-B.View ArticlePubMedGoogle Scholar
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