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Journal of Physiology, Paris Sep 2016The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular... (Review)
Review
The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure.
Topics: Animals; Haplorhini; Receptors, Cholinergic; Receptors, Muscarinic; Receptors, Nicotinic; Serotonergic Neurons; Visual Cortex; Visual Perception
PubMed: 27619519
DOI: 10.1016/j.jphysparis.2016.09.001 -
Allergology International : Official... Jan 2021Cholinergic urticaria (CholU) manifests small, itchy and/or painful wheals occurring upon perspiration and mechanically involving acetylcholine (Ach). Although a... (Review)
Review
Cholinergic urticaria (CholU) manifests small, itchy and/or painful wheals occurring upon perspiration and mechanically involving acetylcholine (Ach). Although a considerable number of studies have been conducted, the pathomechanisms underlying perspiration-associated release of histamine remain to be elucidated. We have proposed that CholU can be categorized into two major subtypes: Ach-indirectly induced, sweat allergic type and Ach-directly induced, depressed sweating type. In the former type, Ach evokes perspiration, and some sweat antigen(s) leaking from the sweat ducts to the dermis may stimulate mast cells to release histamine. In this scenario, the ducts might be damaged or obstructed for sweat leakage, and patients frequently exhibit positive autologous sweat skin test, representing "sweat allergy (hypersensitivity)". On the other hand, the latter Ach-mast cell directly interacting type, typically seen as "CholU with anhidrosis and/or hypohidrosis (CUAH)", eccrine sweat gland epithelial cells lack cholinergic receptor M3 expression. The expression of cholinergic receptors is completely absent in the anhidrotic areas and only slightly expressed in the hypohidrotic areas. In the hypohidrotic area, where pinpoint wheal occurs, it is hypothesized that released Ach cannot be completely trapped by cholinergic receptors of eccrine glands and overflows to the adjacent mast cells, leading to wheal formation. Thus, sweat allergy is not a requirement in this depressed sweating type. Although some additional complications, such as angioedema, anaphylaxis, and cold urticaria, have been documented, these two types represent the modes of action of Ach in this enigmatic urticaria.
Topics: Acetylcholine; Allergens; Biomarkers; Disease Susceptibility; Gene Expression Regulation; Histamine; Histamine Release; Humans; Immunoglobulin E; Mast Cells; Receptors, Cholinergic; Skin Tests; Sweat; Urticaria
PubMed: 32565175
DOI: 10.1016/j.alit.2020.05.006 -
Cell Reports Nov 2022Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of...
Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C. elegans ACC-4, a member of a family of acetylcholine receptors, is required in immune activation by defects in the defecation motor program or by pathogen infection. ACC-4 acts postsynaptically in non-cholinergic RIM neurons to regulate several immune genes and a Wnt-mediated host immune response. These findings uncover a gut-brain-microbial axis that uses neural cholinergic signaling and the Wnt pathway to control immune activation in response to alterations in intestinal homeostasis.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Receptors, Cholinergic; Wnt Signaling Pathway; Cholinergic Agents
PubMed: 36323254
DOI: 10.1016/j.celrep.2022.111575 -
The Journal of Investigative... Aug 1997Human epidermal keratinocytes possess cholinergic enzymes, which synthesize and degrade acetylcholine, and express both nicotinic and muscarinic classes of cholinergic... (Review)
Review
Human epidermal keratinocytes possess cholinergic enzymes, which synthesize and degrade acetylcholine, and express both nicotinic and muscarinic classes of cholinergic receptors on their cell surfaces. These receptors bind acetylcholine and initiate cellular response. The presence in keratinocytes of a functional cholinergic system suggests a role for acetylcholine in most, if not all, aspects of keratinocyte function. Autocrine and paracrine acetylcholine are required to sustain the viability of keratinocytes in vitro, and cholinergic drugs can alter keratinocyte proliferation, adhesion, migration, and differentiation. Acetylcholine employs calcium as a mediator for its effects on keratinocytes. In turn, changes in calcium concentration may affect expression and function of keratinocyte cholinergic enzymes and cholinergic receptors. At different stages of their differentiation, keratinocytes may demonstrate unique combinations of cholinergic enzymes and cholinergic receptor types. This would allow basal, prickle, and granular keratinocytes to respond to acetylcholine differently, in accordance with their functions at each stage of keratinocyte development in epidermis.
Topics: Acetylcholine; Animals; Calcium; Cholinergic Agents; Epidermis; Humans; Keratinocytes; Receptors, Cholinergic; Receptors, Muscarinic; Receptors, Nicotinic
PubMed: 9487015
DOI: 10.1038/jidsymp.1997.10 -
Pharmacological Research Apr 2023Within the superfamily of pentameric ligand-gated ion channels, cholinergic nicotinic receptors (nAChRs) were classically identified to mediate synaptic transmission in... (Review)
Review
Within the superfamily of pentameric ligand-gated ion channels, cholinergic nicotinic receptors (nAChRs) were classically identified to mediate synaptic transmission in the nervous system and the neuromuscular junction. The α9 and α10 nAChR subunits were the last ones to be identified. Surprisingly, they do not fall into the dichotomic neuronal/muscle classification of nAChRs. They assemble into heteropentamers with a well-established function as canonical ion channels in inner ear hair cells, where they mediate central nervous system control of auditory and vestibular sensory processing. The present review includes expression, pharmacological, structure-function, molecular evolution and pathophysiological studies, that define receptors composed from α9 and α10 subunits as distant and distinct members within the nAChR family. Thus, although α9 and α10 were initially included within the neuronal subdivision of nAChR subunits, they form a distinct clade within the phylogeny of nAChRs. Following the classification of nAChR subunits based on their main synaptic site of action, α9 and α10 should receive a name in their own right.
Topics: Receptors, Nicotinic; Receptors, Cholinergic; Neurons; Synaptic Transmission
PubMed: 36931539
DOI: 10.1016/j.phrs.2023.106735 -
Mediators of Inflammation 2021The inflammatory storm in the early stage and immunosuppression in the late stage are responsible for the high mortality rates and multiple organ dysfunction in sepsis.... (Review)
Review
The inflammatory storm in the early stage and immunosuppression in the late stage are responsible for the high mortality rates and multiple organ dysfunction in sepsis. In recent years, studies have found that the body's cholinergic system can spontaneously and dynamically regulate inflammation and immunity in sepsis according to the needs of the body. Firstly, the vagus nerve senses and regulates local or systemic inflammation by means of the Cholinergic Anti-inflammatory Pathway (CAP) and activation of 7-nicotinic acetylcholine receptors (7nAChRs); thus, 7nAChRs play important roles for the central nervous system (CNS) to modulate peripheral inflammation; secondly, the activation of muscarinic acetylcholine receptors 1 (M1AChRs) in the forebrain can affect the neurons of the Medullary Visceral Zone (MVZ), the core of CAP, to regulate systemic inflammation and immunity. Based on the critical role of these two cholinergic receptor systems in sepsis, it is necessary to collect and analyze the related findings in recent years to provide ideas for further research studies and clinical applications. By consulting the related literature, we draw some conclusions: MVZ is the primary center for the nervous system to regulate inflammation and immunity. It coordinates not only the sympathetic system and vagus system but also the autonomic nervous system and neuroendocrine system to regulate inflammation and immunity; 7nAChRs are widely expressed in immune cells, neurons, and muscle cells; the activation of 7nAChRs can suppress local and systemic inflammation; the expression of 7nAChRs represents the acute or chronic inflammatory state to a certain extent; M1AChRs are mainly expressed in the advanced centers of the brain and regulate systemic inflammation; neuroinflammation of the MVZ, hypothalamus, and forebrain induced by sepsis not only leads to their dysfunctions but also underlies the regulatory dysfunction on systemic inflammation and immunity. Correcting the neuroinflammation of these regulatory centers and adjusting the function of 7nAChRs and M1AChRs may be two key strategies for the treatment of sepsis in the future.
Topics: Humans; Inflammation; Neuroimmunomodulation; Receptors, Muscarinic; Sepsis; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 34776789
DOI: 10.1155/2021/9059601 -
The Journal of General Physiology May 2018The muscle acetylcholine (ACh) receptor transduces a chemical into an electrical signal, but the efficiency of transduction, or efficacy, depends on the particular...
The muscle acetylcholine (ACh) receptor transduces a chemical into an electrical signal, but the efficiency of transduction, or efficacy, depends on the particular agonist. It is often presumed that full and partial agonists elicit the same structural changes after occupancy of their binding sites but with differing speed and efficiency. In this study, we tested the alternative hypothesis that full and partial agonists elicit distinct structural changes. To probe structural changes, we substituted cysteines for pairs of residues that are juxtaposed in the three-dimensional structure and recorded agonist-elicited single-channel currents before and after the addition of an oxidizing reagent. The results revealed multiple cysteine pairs for which agonist-elicited channel opening changes after oxidative cross-linking. Moreover, we found that the identity of the agonist determined whether cross-linking affects channel opening. For the αD97C/αY127C pair at the principal face of the subunit, cross-linking markedly suppressed channel opening by full but not partial agonists. Conversely, for the αD97C/αK125C pair, cross-linking impaired channel opening by the weak agonist choline but not other full or partial agonists. For the αT51C/αK125C pair, cross-linking enhanced channel opening by the full agonist ACh but not other full or partial agonists. At the complementary face of the subunit, cross-linking between pairs within the same β hairpin suppressed channel opening by ACh, whereas cross-linking between pairs from adjacent β hairpins was without effect for all agonists. In each case, the effects of cross-linking were reversed after addition of a reducing reagent, and receptors with single cysteine substitutions remained unaltered after addition of either oxidizing or reducing reagents. These findings show that, in the course of opening the receptor channel, different agonists elicit distinct structural changes.
Topics: Amino Acid Substitution; Cell Line; Cross-Linking Reagents; Cysteine; Dithiothreitol; Humans; Hydrogen Peroxide; Ion Channel Gating; Receptors, Cholinergic; Sulfhydryl Reagents
PubMed: 29680816
DOI: 10.1085/jgp.201711881 -
Cell Reports Dec 2017Although much progress has been made in understanding type II theta rhythm generation under urethane anesthesia, less is known about the mechanisms underlying type I...
Although much progress has been made in understanding type II theta rhythm generation under urethane anesthesia, less is known about the mechanisms underlying type I theta generation during active exploration. To better understand the contributions of cholinergic and NMDA receptor activation to type I theta generation, we recorded hippocampal theta oscillations from freely moving mice with local infusion of cholinergic or NMDA receptor antagonists to either the hippocampus or the entorhinal cortex (EC). We found that cholinergic receptors in the hippocampus, but not the EC, and NMDA receptors in the EC, but not the hippocampus, are critical for open-field theta generation and Y-maze performance. We further found that muscarinic M1 receptors located on pyramidal neurons, but not interneurons, are critical for cholinergic modulation of hippocampal synapses, theta generation, and Y-maze performance. These results suggest that hippocampus and EC neurons recruit cholinergic-dependent and NMDA-receptor-dependent mechanisms, respectively, to generate theta oscillations to support behavioral performance.
Topics: Animals; Entorhinal Cortex; Hippocampus; Interneurons; Mice; Mice, Inbred C57BL; Pyramidal Cells; Receptor, Muscarinic M1; Receptors, Cholinergic; Receptors, N-Methyl-D-Aspartate; Theta Rhythm
PubMed: 29262336
DOI: 10.1016/j.celrep.2017.11.080 -
Hearing Research Mar 2011The hair cells of the vertebrate inner ear posses active mechanical processes to amplify their inputs. The stereocilia bundle of various vertebrate animals can produce... (Comparative Study)
Comparative Study Review
The hair cells of the vertebrate inner ear posses active mechanical processes to amplify their inputs. The stereocilia bundle of various vertebrate animals can produce active movements. Though standard stereocilia-based mechanisms to promote amplification persist in mammals, an additional radically different mechanism evolved: the so-called somatic electromotility which refers to the elongation/contraction of the outer hair cells' (OHC) cylindrical cell body in response to membrane voltage changes. Somatic electromotility in OHCs, as the basis for cochlear amplification, is a mammalian novelty and it is largely dependent upon the properties of the unique motor protein prestin. We review recent literature which has demonstrated that although the gene encoding prestin is present in all vertebrate species, mammalian prestin has been under positive selective pressure to acquire motor properties, probably rendering it fit to serve somatic motility in outer hair cells. Moreover, we discuss data which indicates that a modified α10 nicotinic cholinergic receptor subunit has co-evolved in mammals, most likely to give the auditory feedback system the capability to control somatic electromotility.
Topics: Amino Acid Sequence; Animals; Biomechanical Phenomena; Hair Cells, Auditory, Outer; Hearing; Mammals; Molecular Motor Proteins; Molecular Sequence Data; Receptors, Cholinergic
PubMed: 20056140
DOI: 10.1016/j.heares.2009.12.028 -
American Journal of Obstetrics and... Jan 2023The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies... (Review)
Review
OBJECTIVE
The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes.
DATA SOURCES
We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021.
STUDY ELIGIBILITY CRITERIA
Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone.
METHODS
A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder.
RESULTS
A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes.
CONCLUSION
Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.
Topics: Humans; Urinary Bladder, Overactive; TRPV Cation Channels; Genetic Markers; Cholinergic Antagonists; Receptors, Cholinergic; Receptors, Purinergic; Receptor, Muscarinic M3
PubMed: 35932882
DOI: 10.1016/j.ajog.2022.07.044