Nicotinic cholinergic intercellular communication: Implications for the developing auditory system

Morley, Barbara J.

doi:10.1016/j.heares.2005.02.012

Cited by 22 publications

(19 citation statements)

References 212 publications

(223 reference statements)

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“…Moreover, additional studies are required to assess whether sensory and/or cognitive mechanisms of auditory deviance detection are impacted by cholinergic stimulation. As nAChRs are found throughout midbrain and brainstem tracts of the auditory pathway (Habbicht and Vater 1996;Happe and Morley 1998;Happe and Morley 2004;Morley 2005), both regions being shown to display deviance detection properties (Escera et al 2013), the use of early latency ERPs components (<100 ms) may be important in mapping the extent to which α7 receptor modulation affects deviance processing along the auditory hierarchy.…”

Section: Limitationsmentioning

confidence: 99%

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

Knott

Impey

Choueiry

et al. 2015

Neuropsychiatr Electrophysiol

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Background: Alpha 7 nicotinic acetylcholine receptors (α7 nAChR) are prioritized molecular targets for the development of new pharmacological treatments for impaired cognition in schizophrenia. The use of schizophrenia-associated biomarkers both as endpoints and for segmentation of homogeneous populations for early detection of cognitive enhancing agents has been advanced to enhance the drug discovery process. Methods: In this study, the mismatch negativity (MMN) event-related brain potential (ERP), considered one of the few fully developed biomarkers in schizophrenia, was employed: a) to stratify 24 healthy volunteers into subgroups exhibiting low, medium, or high auditory sensory discrimination based on pre-attentive detection of deviant auditory features, and b) to assess their acute response to a low (500 mg) and moderate dose (1000 mg) of CDP-choline, a dietary supplement with selective agonist actions at α7 nAChRs.

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Section: Limitationsmentioning

confidence: 99%

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

Knott

Impey

Choueiry

et al. 2015

Neuropsychiatr Electrophysiol

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“…Most of the auditory pathways within the brain stem are mediated by cholinergic neurotransmission and the predominant nAChR expressed in the lower auditory brainstem nuclei is the α7 subtype, while α3β4 nAChR also plays a role but rather in the development of the auditory brainstem system [200].…”

Section: +mentioning

confidence: 99%

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

Quednow

Brzózka

Rossner

2014

Cell. Mol. Life Sci.

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Schizophrenia is a genetically complex disease considered to have a neurodevelopmental pathogenesis and defined by a broad spectrum of positive and negative symptoms as well as cognitive deficits. Recently, large genome-wide association studies have identified common alleles slightly increasing the risk for schizophrenia. Among the few schizophrenia-risk genes that have been consistently replicated is the basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4). Haploinsufficiency of the TCF4 (formatting follows IUPAC nomenclature: TCF4 protein/protein function, Tcf4 rodent gene cDNA mRNA, TCF4 human gene cDNA mRNA) gene causes the Pitt-Hopkins syndrome-a neurodevelopmental disease characterized by severe mental retardation. Accordingly, Tcf4 null-mutant mice display developmental brain defects. TCF4-associated risk alleles are located in putative coding and non-coding regions of the gene. Hence, subtle changes at the level of gene expression might be relevant for the etiopathology of schizophrenia. Behavioural phenotypes obtained with a mouse model of slightly increased gene dosage and electrophysiological investigations with human risk-allele carriers revealed an overlapping spectrum of schizophrenia-relevant endophenotypes. Most prominently, early information processing and higher cognitive functions appear to be associated with TCF4 risk genotypes. Moreover, a recent human study unravelled gene × environment interactions between TCF4 risk alleles and smoking behaviour that were specifically associated with disrupted early information processing. Taken together, TCF4 is considered as an integrator ('hub') of several bHLH networks controlling critical steps of various developmental, and, possibly, plasticity-related transcriptional programs in the CNS and changes of TCF4 expression also appear to affect brain networks important for information processing. Consequently, these findings support the neurodevelopmental hypothesis of schizophrenia and provide a basis for identifying the underlying molecular mechanisms. AbstractSchizophrenia is a genetically complex disease considered to have a neurodevelopmental pathogenesis and defined by a broad spectrum of positive and negative symptoms as well as cognitive deficits.Recently, large genome-wide association studies have identified common alleles slightly increasing the risk for schizophrenia. Among the few schizophrenia-risk genes that have been consistently replicated is the basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4 behaviour that were specifically associated with disrupted early information processing. Taken together, TCF4 is considered as an integrator ('hub') of several bHLH networks controlling critical steps of various developmental and possibly also plasticity related transcriptional programs in the CNS and changes of TCF4 expression appear to affect brain networks important for information processing.Consequently, these findings support the neurodevelopmental hypothesis of schizophrenia and provide a basis to identify the und...

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“…, ; Morley and Happe ; Katz et al. ; Morley ). This functional diversity is in part accomplished through strict spatiotemporal control of different nAChR subunit expression, as has been extensively described for the nAChRs composed of either homomeric (α9) or heteromeric (α9 + α10) subunits (Elgoyhen et al.…”

Section: Introductionmentioning

confidence: 99%

“…Members of the nAChR family contribute to essentially all aspects of the auditory sensory system function and development (Morley and Happe ; Morley ). This includes widespread changes in expression during embryogenesis that optimizes their contribution to signal transduction, fine‐tuning of sensory hair cells, and modulating central auditory circuit neurotransmission (Elgoyhen et al.…”

Section: Introductionmentioning

confidence: 99%

The expression of nicotinic receptor alpha7 during cochlear development

2012

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Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively. The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers. This pattern diminishes after E16.5 in a basal to apex progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP expression. At birth and thereafter alpha7GFP also identifies a subset of spiral ganglion cells whose processes terminate on inner hair cells. Efferent fibers identified by peripherin or calcitonin gene-related protein do not coexpress alpha7GFP. In addition to cochlear structures, there is strong expression of alpha7GFP by cells of the central auditory pathways including the ventral posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and the medial geniculate nucleus. Our findings suggest that alpha7 expression by both neuronal and non-neuronal cells has the potential to impact multiple auditory functions through mechanisms that are not traditionally attributed to this receptor.

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Nicotinic cholinergic intercellular communication: Implications for the developing auditory system

Cited by 22 publications

References 212 publications

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective

The expression of nicotinic receptor alpha7 during cochlear development

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