scholarly journals Nicotinic acetylcholine receptor-mediated responses in medial vestibular and prepositus hypoglossi nuclei neurons showing distinct neurotransmitter phenotypes

2016 ◽  
Vol 115 (5) ◽  
pp. 2649-2657 ◽  
Author(s):  
Yue Zhang ◽  
Yuchio Yanagawa ◽  
Yasuhiko Saito
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Vestibular Nucleus ◽  
Expression Patterns ◽  
Muscarinic Acetylcholine Receptors ◽  
Medial Vestibular Nucleus ◽  
Nicotinic Acetylcholine ◽  
Decay Times ◽  
Prepositus Hypoglossi ◽  
Α7 Nachrs

Cholinergic transmission in both the medial vestibular nucleus (MVN) and prepositus hypoglossi nucleus (PHN) plays an important role in horizontal eye movements. We previously demonstrated that the current responses mediated via nicotinic acetylcholine receptors (nAChRs) were larger than those mediated via muscarinic acetylcholine receptors (mAChRs) in cholinergic MVN and PHN neurons that project to the cerebellum. In this study, to clarify the predominant nAChR responses and the expression patterns of nAChRs in MVN and PHN neurons that exhibit distinct neurotransmitter phenotypes, we identified cholinergic, inhibitory, and glutamatergic neurons using specific transgenic rats and investigated current responses to the application of acetylcholine (ACh) using whole cell recordings in brain stem slices. ACh application induced larger nAChR-mediated currents than mAChR-mediated currents in every neuronal phenotype. In the presence of an mAChR antagonist, we found three types of nAChR-mediated currents that exhibited different rise and decay times and designated these as fast (F)-, slow (S)-, and fast and slow (FS)-type currents. F-type currents were the predominant response in inhibitory MVN neurons, whereas S-type currents were observed in the majority of glutamatergic MVN and PHN neurons. No dominant response type was observed in cholinergic neurons. Pharmacological analyses revealed that the F-, S-, and FS-type currents were mainly mediated by α7, non-α7, and both α7 and non-α7 nAChRs, respectively. These findings suggest that cholinergic responses in the major neuronal populations of the MVN and PHN are predominantly mediated by nAChRs and that the expression of α7 and non-α7 nAChRs differ among the neuronal phenotypes.

scholarly journals Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice

2021 ◽  
Vol 22 (14) ◽  
pp. 7251
Author(s):  
Petrilla Jayaprakash ◽  
Dmytro Isaev ◽  
Waheed Shabbir ◽  
Dietrich E. Lorke ◽  
Bassem Sadek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Pathological Condition ◽  
Repetitive Behaviors ◽  
Social Deficits ◽  
Nicotinic Acetylcholine ◽  
Oxidative Stress Status ◽  
Inward Currents ◽  
Α7 Nachrs

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.

scholarly journals Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 164
Author(s):  
Lina Son ◽  
Elena Kryukova ◽  
Rustam Ziganshin ◽  
Tatyana Andreeva ◽  
Denis Kudryavtsev ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Central Loop ◽  
Acetylcholine Binding Proteins ◽  
Α7 Nachrs

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

Nicotinic Acetylcholine Receptors Contribute to Learning-induced Metaplasticity in the Hippocampus

2013 ◽  
Vol 25 (7) ◽  
pp. 986-997 ◽  
Author(s):  
Benjamin Becker ◽  
Eva M. Klein ◽  
Nadine Striepens ◽  
Yoan Mihov ◽  
Thomas E. Schlaepfer ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Low Dose ◽  
Controlled Trial ◽  
Treated Group ◽  
Nicotinic Acetylcholine ◽  
Behavioral Learning ◽  
Subsequent Learning ◽  
Per Se ◽  
Α7 Nachrs

Hippocampal learning is thought to induce metaplasticity, which can facilitate subsequent learning. Administered at single low doses, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine predominantly blocks α7 nicotinic acetylcholine receptors (α7 nAChRs). Placebo-controlled administration of a single low dose of memantine in a pharmaco-fMRI experiment may thus help characterize the role of α7 nAChRs in hippocampal metaplasticity. We hypothesized that if α7 nAChRs contribute to learning-induced metaplasticity in the hippocampus, blockade of these receptors with low-dose memantine would selectively interfere with a facilitation of subsequent learning without impairing hippocampal learning per se. To specifically test this hypothesis, we devised a randomized controlled trial in which healthy volunteers were administered a 20-mg single oral dose of memantine or placebo and scanned on three subsequent runs of a hippocampal learning task. Our results indicate no discrepancies in behavioral learning between low-dose memantine- and placebo-treated participants in the first and second run of this task. In the third run, however, only the placebo-treated group showed facilitated behavioral learning, an effect paralleled by decreased neural responses in the hippocampal cornu ammonis region. Our findings suggest that blockade of α7 nAChRs selectively interfered with a learning-induced facilitation of subsequent learning while leaving unimpaired hippocampal learning per se. Taken together, our results provide support for a relevant contribution of α7 nAChRs to learning-associated metaplasticity in the hippocampus.

scholarly journals Nicotinic acetylcholine receptor partial antagonist polyamides from tunicates and their predatory sea slugs

2021 ◽  
Author(s):  
Noemi D. Paguigan ◽  
Jortan O. Tun ◽  
Lee S. Leavitt ◽  
Zhenjian Lin ◽  
Kevin Chase ◽  
...  
Keyword(s):  
Nervous System ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Partial Agonist ◽  
Muscarinic Acetylcholine Receptors ◽  
New Drugs ◽  
Calcium Flux ◽  
Nicotinic Acetylcholine ◽  
Chemical Structures ◽  
Α7 Nachr

In our efforts to discover new drugs to treat pain, we identified molleamines A-E (1-5) as major neuroactive components of the sea slug, Pleurobranchus forskalii and their prey, Didemnum molle tunicates. The chemical structures of molleamines were elucidated by spectroscopy and confirmed by the total synthesis of molleamines A (1) and C (3). Synthetic 3 completely blocked acetylcholine-induced calcium flux in peptidergic nociceptors (PNs) in the somatosensory nervous system. Compound 3 affected neither the α7 nAChR nor the muscarinic acetylcholine receptors in calcium flux assays. In addition to nociceptors, 3 partially blocked the acetylcholine-induced calcium flux in the sympathetic nervous system, including neurons from the superior cervical ganglion. Electrophysiology revealed a block of α3β4 (mouse) and α6/α3β4 (rat) nicotinic acetylcholine receptors (nAChRs), with IC50 values of 1.4 and 3.1 μM, respectively. Molleamine C (3) is a partial antagonist, reaching a maximum block of 76-82% of the acetylcholine signal and showing no partial agonist response. Molleamine C (3) may thus provide a lead compound for the development of neuroactive compounds with unique biological properties.

Imidacloprid actions on insect neuronal acetylcholine receptors

1997 ◽  
Vol 200 (21) ◽  
pp. 2685-2692 ◽  
Author(s):  
S Buckingham ◽  
B Lapied ◽  
H Corronc ◽  
F Sattelle
Keyword(s):  
Nervous System ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Periplaneta Americana ◽  
Muscarinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Neonicotinoid Insecticide ◽  
Dose Dependent ◽  
Dorsal Unpaired Median ◽  
Giant Interneurone

The neonicotinoid insecticide Imidacloprid acts at three pharmacologically distinct acetylcholine receptor (AChR) subtypes in the cockroach (Periplaneta americana) nervous system, but is ineffective on muscarinic receptors. Imidacloprid (3-100µmoll-1) induced dose-dependent depolarizations at cockroach cercal afferent/giant interneurone synapses. These responses were insensitive to 20µmoll-1 atropine but were completely blocked by the nicotinic antagonist mecamylamine (50µmoll-1). Similarly, Imidacloprid-induced depolarizations of cultured cockroach dorsal unpaired median (DUM) neurones dissociated from the same (terminal abdominal) ganglion were also completely blocked by 100µmoll-1 mecamylamine. However, two components of the response could be distinguished on the basis of their differential sensitivities to 0.1µmoll-1-bungarotoxin (-BTX), which selectively blocks AChRs with 'mixed' nicotinic/muscarinic pharmacology in this preparation. This indicates that Imidacloprid affects both AChRs sensitive to -BTX and -BTX-insensitive nicotinic acetylcholine receptors (nAChRs). Thus, in the cockroach, Imidacloprid activates -BTX-sensitive synaptic nAChRs in giant interneurones, -BTX-insensitive extrasynaptic nAChRs in DUM neurones, and a recently characterized DUM neurone 'mixed' AChR that is sensitive to both nicotinic and muscarinic ligands. Imidacloprid does not act on muscarinic acetylcholine receptors (mAChRs) present on DUM neurone cell bodies and at the cercal afferent/giant interneurone synapses. This study shows that Imidacloprid can act on pharmacologically diverse nAChR subtypes.

scholarly journals Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

2008 ◽  
Vol 181 (3) ◽  
pp. 511-521 ◽  
Author(s):  
Melissa L. Hancock ◽  
Sarah E. Canetta ◽  
Lorna W. Role ◽  
David A. Talmage
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Surface Expression ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Phosphatidylinositol 3 Kinase ◽  
Nicotinic Acetylcholine ◽  
Type Iii ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Erbb Signaling ◽  
Α7 Nachrs

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

scholarly journals Characterization of nAChRs in Nematostella vectensis supports neuronal and non-neuronal roles in the cnidarian–bilaterian common ancestor

EvoDevo ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Dylan Z. Faltine-Gonzalez ◽  
Michael J. Layden
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Common Ancestor ◽  
Expression Patterns ◽  
Muscarinic Acetylcholine Receptors ◽  
Phylogenetic Position ◽  
Neuronal Function ◽  
Spatiotemporal Expression ◽  
Chemical Synapses ◽  
Neuronal Functions

Abstract Background Nicotinic and muscarinic acetylcholine receptors likely evolved in the cnidarian–bilaterian common ancestor. Both receptor families are best known for their role at chemical synapses in bilaterian animals, but they also have described roles as non-neuronal signaling receptors within the bilaterians. It is not clear when either of the functions for nicotinic or muscarinic receptors evolved. Previous studies in cnidarians suggest that acetylcholine’s neuronal role existed prior to the cnidarian–bilaterian divergence, but did not address potential non-neuronal functions. To determine the origins of neuronal and non-neuronal functions of nicotinic acetylcholine receptors, we investigated the phylogenetic position of cnidarian acetylcholine receptors, characterized the spatiotemporal expression patterns of nicotinic receptors in N. vectensis, and compared pharmacological studies in N. vectensis to the previous work in other cnidarians. Results Consistent with described activity in other cnidarians, treatment with acetylcholine-induced tentacular contractions in the cnidarian sea anemone N. vectensis. Phylogenetic analysis suggests that the N. vectensis genome encodes 26 nicotinic (nAChRs) and no muscarinic (mAChRs) acetylcholine receptors and that nAChRs independently radiated in cnidarian and bilaterian linages. The namesake nAChR agonist, nicotine, induced tentacular contractions similar to those observed with acetylcholine, and the nAChR antagonist mecamylamine suppressed tentacular contractions induced by both acetylcholine and nicotine. This indicated that tentacle contractions are in fact mediated by nAChRs. Nicotine also induced the contraction of radial muscles, which contract as part of the peristaltic waves that propagate along the oral–aboral axis of the trunk. Radial contractions and peristaltic waves were suppressed by mecamylamine. The ability of nicotine to mimic acetylcholine responses, and of mecamylamine to suppress acetylcholine and nicotine-induced contractions, supports a neuronal function for acetylcholine in cnidarians. Examination of the spatiotemporal expression of N. vectensis nAChRs (NvnAChRs) during development and in juvenile polyps identified that NvnAChRs are expressed in neurons, muscles, gonads, and large domains known to be consistent with a role in developmental patterning. These patterns are consistent with nAChRs functioning in both a neuronal and non-neuronal capacity in N. vectensis. Conclusion Our data suggest that nAChR receptors functioned at chemical synapses in N. vectensis to regulate tentacle contraction. Similar responses to acetylcholine are well documented in cnidarians, suggesting that the neuronal function represents an ancestral role for nAChRs. Expression patterns of nAChRs are consistent with both neuronal and non-neuronal roles for acetylcholine in cnidarians. Together, these observations suggest that both neuronal and non-neuronal functions for the ancestral nAChRs were present in the cnidarian–bilaterian common ancestor. Thus, both roles described in bilaterian species likely arose at or near the base of nAChR evolution.

Actions of the insecticide 2 (nitromethylene) tetrahydro-1, 3-thiazine on insect and vertebrate nicotinic acetylcholine receptors

1989 ◽  
Vol 237 (1289) ◽  
pp. 501-514 ◽  
Keyword(s):  
Rat Brain ◽  
Glutamate Receptors ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Reversal Potential ◽  
Muscarinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Agonist Action

The nitromethylene heterocyclic compound 2(nitromethylene)tetrahydro) 1, 3-thiazine (NMTHT) inhibits the binding of [ 125 I) α -bungarotoxin to membranes prepared from cockroach ( Periplaneta americana ) nerve cord and fish ( Torpedo californica ) electric organ. Electrophysiological studies on the cockroach fast coxal depressor motorneuron (D f ) reveal a dose-dependent depolarization in response to bath-applied NMTHT. Responses to ionophoretic application of NMTHT on to the cell-body membrane of motorneuron D f are suppressed by bath-applied mecamylamine (1.0 x 10 -4 M) and α -bungarotoxin (1.0 x 10 -7 M). These findings, together with the detection of a reversal potential close to that estimated for acetylcholine, provide evidence for an agonist action of this nitromethylene on an insect neuronal nicotinic acetylcholine receptor. The binding of [ 3 H]H 12 -histrionicotoxin to Torpedo membranes was enhanced in the presence of NMTHT indicating an agonist action at this vertebrate peripheral nicotinic acetylcholine receptor. NMTHT is ineffective in radioligand binding assays for rat brain GABA A receptors, rat brain L-glutamate receptors and insect ( Musca domestica ) L-glutamate receptors. Partial block of rat brain muscarinic acetylcholine receptors is detected at millimolar concentrations of NMTHT. Thus nitromethylenes appear to exhibit selectivity for acetylcholine receptors and exhibitan agonist action at nicotinic acetylcholine receptors.

scholarly journals Distinct evolutionary trajectories of neuronal and hair cell nicotinic acetylcholine receptors

2019 ◽  
Author(s):  
Irina Marcovich ◽  
Marcelo J. Moglie ◽  
Agustín E. Carpaneto Freixas ◽  
Anabella P. Trigila ◽  
Lucia F. Franchini ◽  
...  
Keyword(s):  
Hair Cell ◽  
Functional Properties ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Expression Patterns ◽  
Nicotinic Acetylcholine ◽  
Coding Sequences ◽  
The Family ◽  
Evolutionary Trajectories ◽  
Cell Expression

ABSTRACTThe expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Remarkably, with a highly conserved vertebrate complement, nicotinic acetylcholine receptors (nAChRs) are unique among ligand-gated ion channels in that members of the family have distinct roles in synaptic transmission in non-overlapping domains, either in the nervous system, the inner ear hair cells or the neuromuscular junction. Here, we performed a comprehensive analysis of vertebrate nAChRs sequences, single cell expression patterns and comparative functional properties of receptors from three representative tetrapod species. We show that hair cell nAChRs underwent a distinct evolutionary trajectory to that of neuronal receptors. These were most likely shaped by different co-expression patterns and co-assembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater co-expression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell α9α10 nAChRs exhibited greater sequence divergence, narrow co-expression pattern and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission.Significance statementOur work exploits several peculiarities of the family of vertebrate nicotinic acetylcholine receptors (nAChRs) to explore the evolutionary trajectories of a ligand-gated ion channel family. By performing a comprehensive comparative analysis of nAChR subunits coding sequences, single cell expression patterns and functional properties we found a contrasting evolutionary history between nAChRs with widespread expression in the nervous system compared to those with isolated expression in the inner ear. Evolutionary changes were focused on differences in co-expression and co-assembly patterns for the former and coding sequences in the latter. This multidisciplinary approach provides further insight into the evolutionary processes that shaped the nervous and sensory systems of extant animals.

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