Parvalbumin, but not calretinin, neurons express high levels of α1-containing GABAA receptors, α7-containing nicotinic acetylcholine receptors and D2-dopamine receptors in the basolateral amygdala of the rat

2017 ◽  
Vol 86 ◽  
pp. 41-51 ◽  
Author(s):  
Maciej Równiak ◽  
Małgorzata Kolenkiewicz ◽  
Anna Kozłowska
Keyword(s):  
Dopamine Receptors ◽  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Acetylcholine Receptors ◽  
Basolateral Amygdala ◽  
D2 Dopamine Receptors ◽  
Nicotinic Acetylcholine

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.

scholarly journals Activation of Nicotinic Acetylcholine Receptors Increases the Frequency of Spontaneous GABAergic IPSCs in Rat Basolateral Amygdala Neurons

2005 ◽  
Vol 94 (5) ◽  
pp. 3081-3091 ◽  
Author(s):  
Ping Jun Zhu ◽  
Randall R. Stewart ◽  
J. Michael McIntosh ◽  
Forrest F. Weight
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Basolateral Amygdala ◽  
Bathing Solution ◽  
Patch Clamp Recording ◽  
Nicotinic Acetylcholine ◽  
Whole Cell Patch Clamp ◽  
Agonist And Antagonist ◽  
Subunit Combination ◽  
Conditioned Responses

The basolateral amygdala (BLA) is a critical component of the amygdaloid circuit, which is thought to be involved in fear conditioned responses. Using whole cell patch-clamp recording, we found that activation of nicotinic acetylcholine receptors (nAChRs) leads to an action potential-dependent increase in the frequency of spontaneous GABAergic currents in principal neurons in the BLA. These spontaneous GABAergic currents were abolished by a low-Ca2+/high-Mg2+ bathing solution, suggesting that they are spontaneous inhibitory postsynaptic currents (sIPSCs). Blockade of ionotropic glutamate receptors did not prevent this increased frequency of sIPSCs nor did blockade of α7 nAChRs. Among the nAChR agonists tested, cystisine was more effective at increasing the frequency of the sIPSCs than nicotine or 1,1-dimethyl-4-phenyl piperazinium iodide, consistent with a major contribution of β4 nAChR subunits. The nicotinic antagonist, dihydro-β-erythroidine, was less effective than d-tubocurarine in blocking the increased sIPSC frequency induced by ACh, suggesting that α4-containing nAChR subunits do not play a major role in the ACh-induced increased sIPSC frequency. Although α2/3/4/7 and β2/4 nAChR subunits were found in the BLA by RT-PCR, the agonist and antagonist profiles suggest that the ACh-induced increase in sIPSC frequency involves predominantly α3β4-containing nAChR subunits. Consistent with this, α-conotoxin-AuIB, a nAChR antagonist selective for the α3β4 subunit combination, inhibited the ACh-induced increase in the frequency of sIPSCs. The observations suggest that nicotinic activation increases the frequency of sIPSCs in the BLA by acting mainly on α3β4-containing nicotinic receptors on GABAergic neurons and may play an important role in the modulation of synaptic transmission in the amygdala.

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 α7-Containing nicotinic acetylcholine receptors on interneurons of the basolateral amygdala and their role in the regulation of the network excitability

2013 ◽  
Vol 110 (10) ◽  
pp. 2358-2369 ◽  
Author(s):  
Volodymyr I. Pidoplichko ◽  
Eric M. Prager ◽  
Vassiliki Aroniadou-Anderjaska ◽  
Maria F. M. Braga
Keyword(s):  
Emotional Disorders ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Basolateral Amygdala ◽  
Emotional Behavior ◽  
Mental Illnesses ◽  
Nicotinic Acetylcholine ◽  
Normal Functions ◽  
Whole Cell Recordings

The basolateral amygdala (BLA) plays a key role in fear-related learning and memory, in the modulation of cognitive functions, and in the overall regulation of emotional behavior. Pathophysiological alterations involving hyperexcitability in this brain region underlie anxiety and other emotional disorders as well as some forms of epilepsy. GABAergic interneurons exert a tight inhibitory control over the BLA network; understanding the mechanisms that regulate their activity is necessary for understanding physiological and disordered BLA functions. The BLA receives dense cholinergic input from the basal forebrain, affecting both normal functions and dysfunctions of the amygdala, but the mechanisms involved in the cholinergic regulation of inhibitory activity in the BLA are unclear. Using whole cell recordings in rat amygdala slices, here we demonstrate that the α7-containing nicotinic acetylcholine receptors (α7-nAChRs) are present on somatic or somatodendritic regions of BLA interneurons. These receptors are active in the basal state enhancing GABAergic inhibition, and their further, exogenous activation produces a transient but dramatic increase of spontaneous inhibitory postsynaptic currents in principal BLA neurons. In the absence of AMPA/kainate receptor antagonists, activation of α7-nAChRs in the BLA network increases both GABAergic and glutamatergic spontaneous currents in BLA principal cells, but the inhibitory currents are enhanced significantly more than the excitatory currents, reducing overall excitability. The anxiolytic effects of nicotine as well as the role of the α7-nAChRs in seizure activity involving the amygdala and in mental illnesses, such as schizophrenia and Alzheimer's disease, may be better understood in light of the present findings.

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.

scholarly journals Activation of Alpha7 Nicotinic Acetylcholine Receptors Reduce Chronic Pain-Induced Depression-Like Behaviors Via WNT/β-Catenin Pathway

2021 ◽  
Author(s):  
Yongmei Chen ◽  
Xingrui Gong ◽  
Wen Wen ◽  
Meihua Cai ◽  
Mazhong Zhang
Keyword(s):  
Chronic Pain ◽  
Inflammatory Response ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Basolateral Amygdala ◽  
Brain Inflammation ◽  
Common Mechanism ◽  
Nicotinic Acetylcholine ◽  
Male Wistar Rats ◽  
Anti Inflammatory

Abstract Chronic pain frequently leads to depression and microglia-related inflammation is the common mechanism for chronic pain and depression. Activation of alpha 7 nicotinic acetylcholine (α7 nAch) receptor suppresses microglia-related inflammation. Thus, we evaluated the activation of α7 nAch receptors on chronic pain-induced depression-like behaviors and explored the potential mechanisms.Methods: Male Wistar rats that received spared nerve injury (SNI) and complete Freund’s adjuvant (CFA) into the unilateral ankle articular cavity received Open field, sucrose preference, and pain behavior tests. The effect of intracerebroventricular (ICV) injection of α7 nAch receptor agonist PHA and α7 nAch receptor antagonist on depression-like behaviors and cytokines expression was examined. Cytokines were measured in the brain using Enzyme-linked immune absorbent assay.Results: SNI surgery and CFA injection induced depression-like behaviors, and ICV injection of PHA reduced that depression-like behaviors. SNI surgery and CFA injection skewed the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus to a pro-inflammatory response and ICV injection of PHA shift brain from pro-inflammatory to anti-inflammatory response in that sites. The anti-depressive effect and anti-inflammatory effect of PHA were reversed by WNT/β-catenin inhibitor. Conclusions: Activation of alpha7 nicotinic acetylcholine receptors reduce chronic pain-induced depression-like behaviors, the mechanisms may be attributed to the activation of WNT/β-catenin pathway and suppression of brain inflammation.

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