scholarly journals Corelease of acetylcholine and GABA from cholinergic forebrain neurons

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Arpiar Saunders ◽  
Adam J Granger ◽  
Bernardo L Sabatini
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Cholinergic System ◽  
Acetylcholine Receptors ◽  
Cholinergic Neurons ◽  
Cortical Function ◽  
Nicotinic Acetylcholine ◽  
Full Extent ◽  
Anatomical Analysis ◽  
Forebrain Neurons

Neurotransmitter corelease is emerging as a common theme of central neuromodulatory systems. Though corelease of glutamate or GABA with acetylcholine has been reported within the cholinergic system, the full extent is unknown. To explore synaptic signaling of cholinergic forebrain neurons, we activated choline acetyltransferase expressing neurons using channelrhodopsin while recording post-synaptic currents (PSCs) in layer 1 interneurons. Surprisingly, we observed PSCs mediated by GABAA receptors in addition to nicotinic acetylcholine receptors. Based on PSC latency and pharmacological sensitivity, our results suggest monosynaptic release of both GABA and ACh. Anatomical analysis showed that forebrain cholinergic neurons express the GABA synthetic enzyme Gad2 and the vesicular GABA transporter (Slc32a1). We confirmed the direct release of GABA by knocking out Slc32a1 from cholinergic neurons. Our results identify GABA as an overlooked fast neurotransmitter utilized throughout the forebrain cholinergic system. GABA/ACh corelease may have major implications for modulation of cortical function by cholinergic neurons.

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.

Human Nicotinic Acetylcholine Receptors: Part II. Non-Neuronal Cholinergic System

2019 ◽  
Vol 45 (2) ◽  
pp. 66-75 ◽  
Author(s):  
M. A. Shulepko ◽  
D. S. Kulbatskii ◽  
M. L. Bychkov ◽  
E. N. Lyukmanova
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cholinergic System ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine

Ontogenesis of nicotinic acetylcholine receptors and presynaptic cholinergic neurons in mammalian brain

Life Sciences ◽  
1986 ◽  
Vol 38 (7) ◽  
pp. 637-644 ◽  
Author(s):  
Shizuo Yamada ◽  
Yoshiyuki Kagawa ◽  
Mitsutaka Isogai ◽  
Noriyasu Takayanagi ◽  
Eiichi Hayashi
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Cholinergic Neurons ◽  
Mammalian Brain ◽  
Nicotinic Acetylcholine

scholarly journals Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence

2019 ◽  
Vol 41 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Cheng Xiao ◽  
Chun-yi Zhou ◽  
Jin-hong Jiang ◽  
Cui Yin
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cholinergic System ◽  
Acetylcholine Receptors ◽  
Drug Targets ◽  
Clinical Investigation ◽  
Nicotinic Acetylcholine ◽  
Smoking Intervention ◽  
Cholinergic Regulation ◽  
Midbrain Dopaminergic Neurons ◽  
Activity Dependent

Abstract Midbrain dopaminergic (DA) neurons are governed by an endogenous cholinergic system, originated in the mesopontine nuclei. Nicotine hijacks nicotinic acetylcholine receptors (nAChRs) and interferes with physiological function of the cholinergic system. In this review, we describe the anatomical organization of the cholinergic system and the key nAChR subtypes mediating cholinergic regulation of DA transmission and nicotine reward and dependence, in an effort to identify potential targets for smoking intervention. Cholinergic modulation of midbrain DA systems relies on topographic organization of mesopontine cholinergic projections, and activation of nAChRs in midbrain DA neurons. Previous studies have revealed that α4, α6, and β2 subunit-containing nAChRs expressed in midbrain DA neurons and their terminals in the striatum regulate firings of midbrain DA neurons and activity-dependent dopamine release in the striatum. These nAChRs undergo modification upon chronic nicotine exposure. Clinical investigation has demonstrated that partial agonists of these receptors elevate the success rate of smoking cessation relative to placebo. However, further investigations are required to refine the drug targets to mitigate unpleasant side-effects.

scholarly journals Habenula cholinergic neurons regulate anxiety during nicotine withdrawal via nicotinic acetylcholine receptors

2016 ◽  
Vol 107 ◽  
pp. 294-304 ◽  
Author(s):  
Xueyan Pang ◽  
Liwang Liu ◽  
Jennifer Ngolab ◽  
Rubing Zhao-Shea ◽  
J. Michael McIntosh ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Cholinergic Neurons ◽  
Nicotine Withdrawal ◽  
Nicotinic Acetylcholine

Cholinoceptive neurons in the retina of the chick: an immunohistochemical study of the nicotinic acetylcholine receptors

1988 ◽  
Vol 1 (4) ◽  
pp. 349-366 ◽  
Author(s):  
K.T. Keyser ◽  
T.E. Hughes ◽  
P.J. Whiting ◽  
J.M. Lindstrom ◽  
H.J. Karten
Keyword(s):  
Monoclonal Antibodies ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Ganglion Cells ◽  
Cholinergic Neurons ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Inner Plexiform Layer ◽  
Nicotinic Acetylcholine ◽  
Chick Retina

AbstractMonoclonal antibodies directed against nicotinic acetylcholine receptors (nAChRs) were used to identify and characterize cholinoceptive neurons in the chick retina. Two monoclonal antibodies (mAbs), mAb 210 and mAb 270, stained many neurons in both the inner nuclear layer (INL) and ganglion cell layer (GCL). A class of large labeled cells in the inner INL were positioned at the INL/IPL (inner plexiform layer) border and resembled displaced ganglion cells (DGCs). Their identity was confirmed with injections of rhodamine-labeled microspheres into the ventral tectum and nucleus of the basal optic root (nBOR). Four days after the injection, large nAChR-positive neurons in the inner INL were labeled with beads. The distribution of these cells matched that reported for DGCs in the chicken and pigeon (Reiner et al., 1979; Fite et al., 1981). Many smaller cells in the INL also exhibited nAChR immunoreactivity. These cells were not retrogradely labeled after bead injections into retinal recipient areas. Their processes entered the IPL where they arborized in a band comprised of the inner leaflet of lamina 1 and all of lamina 2. In some instances, a process continued inward to lamina 4. These neurons were tentatively identified as amacrine cells because of their position and branching pattern.Approximately 12–18% of the cells in the GCL exhibited nAChR immunoreactivity. Many of these cells could be classified as ganglion cells as their axons were also labeled following exposure to nAChR antibodies. Their distribution mirrored that of all ganglion cells with a higher density of cells in the central retina than in the periphery (Ehrlich, 1981). A “double label” technique was used to compare the distribution of nAChR-positive neurons with that of the choline acetyltransferase-positive (ChAT), cholinergic neurons in the chick retina. The two antigens were visualized with two different fluorophores: FITC and RITC. We were unable to find any cells in either the INL or GCL that exhibited both ChAT- and nAChR-like immunoreactivity. The nAChR-positive cells and the ChAT-positive cells both arborized in two bands within the IPL. The patterns were in perfect register in the inner IPL (lamina 4). But, in the outer IPL, the nAChR-positive dendrites were observed in the inner leaflet of lamina 1 and in all of lamina 2 while the ChAT-positive dendrites did not extend into the innermost portion of lamina 2.

Effects of Thiopental and Its Optical Isomers on Nicotinic Acetylcholine Receptors

2000 ◽  
Vol 93 (3) ◽  
pp. 774-783 ◽  
Author(s):  
David L. Downie ◽  
Nicholas P. Franks ◽  
William R. Lieb
Keyword(s):  
General Anesthesia ◽  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Acetylcholine Receptors ◽  
Optical Isomers ◽  
Nicotinic Acetylcholine ◽  
Peripheral Muscle ◽  
Low Concentrations ◽  
High Concentrations

Background With the exception of gamma-aminobutyric acidA (GABAA) receptors, the major molecular targets underlying the anesthetizing actions of thiopental have yet to be established. Neuronal nicotinic acetylcholine receptors (nAChRs) are closely related to GABAA receptors and hence might also be major targets. If so, they might be expected to be substantially inhibited by surgical concentrations (EC50 = 25 micrometer) of thiopental and to display the same stereoselectivity as does general anesthesia. Methods Neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs were expressed in Xenopus oocytes. Peak acetylcholine-activated currents were measured at -70 mV using the two-electrode voltage clamp technique. Racemic thiopental and its two optical isomers were applied with and without preincubation and at high and low concentrations of acetylcholine. Results Inhibition of all three nAChRs was enhanced by preincubation with thiopental, a protocol that mimics the pharmacologic situation in vivo. Using this protocol, inhibition was further enhanced by high concentrations of acetylcholine, with IC50 = 18 +/- 2, 34 +/- 4, and 20 +/- 2 micrometer (mean +/- SEM) thiopental for the neuronal alpha4beta2, neuronal alpha7 and muscle alphabetagammadelta nAChRs, respectively, with Hill coefficients near unity. Neither the neuronal alpha7 nor the muscle alphabetagammadelta nAChR differentiated between the optical isomers of thiopental. However, R(+)-thiopental was significantly more effective than the S(-) isomer at inhibiting the neuronal alpha4beta2 nAChR; interestingly, this is diametrically opposite to their stereoselectivity for general anesthesia. Conclusions Both central neuronal and peripheral muscle nAChRs can be substantially inhibited by thiopental at surgical EC50 concentrations but with either no stereoselectivity or one opposite to that for general anesthesia. Thus, nAChRs are probably not crucial targets for producing thiopental anesthesia, although nAChRs may play a part in the side effects produced by this agent.

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