Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetically modified muscarinic acetylcholine receptors (mAChRs) that have minimal responsiveness to acetylcholine (ACh) but are potently and efficaciously activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). DREADDs have been used as tools for selectively modulating signal transduction pathways ...

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder. Since acetylcholine (ACh) is known to participate in the inflammatory response, we investigated the possible relationship between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis (RR-MS) patients. Levels of ACh and pro-inflammatory cytokines IL1-β a...

A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron micros...

Previous studies in our laboratory have found that muscle atonia could be triggered by two distinct areas of the medial medulla, a caudal region, corresponding to the nucleus paramedianus (NPM) and a rostral region, corresponding to the nucleus magnocellularis (NMC). The former region is responsive to acetylcholine (ACh) and the latter region is responsive to glutamate. In this study we have me...

Neonatal mice resist the lethal effect of Waglerin-1. Because Waglerin-1 blocks the nicotinic acetylcholine receptor of mature end-plates, the appearance of lethality may result from the epsilon- for gamma-subunit substitution. In support of this hypothesis, adult knockout (KO) mice lacking the gene coding for the epsilon-subunit resist the lethal effect of Waglerin-1. In contrast, heterozygous...

Nicotinic acetylcholine receptors (nAChR) of the TE671 cell line were investigated using whole-cell and membrane patch recording techniques. At negative holding potentials (VH), pulses of acetylcholine (ACh) elicited whole-cell inward currents that rapidly desensitized. The EC50 value for ACh at VH = -60 mV was 7.8 microM. The ACh-induced current reversed at approximately 0 mV. Desensitization ...

5-HT4 receptor (5-HT4R) activation induces pro-cognitive effects. This might be related to stimulation of hippocampal acetylcholine (ACh) release, which has been shown for 5-HT4R agonists in in vivo models. We investigated the influence of the 5-HT4R agonists prucalopride and BIMU-8 on ACh release in rat hippocampal brain slices. In contrast to the report by Siniscalchi et al. [1], no facilitat...

Acetylcholine (ACh)-receptor ion channels were investigated under the modulatory action of calcium and cyclic AMP in completely isolated Lymnaea stagnalis neurones using the noise analysis technique. Elevation of the intracellular Ca2+ concentration in dialyzed neurones produced a reduction in the amplitude of ACh induced current accompanied by slight decrease in the mean channel open time and ...

Acetylcholine (ACh) signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) by ACh alters the activation state of neurons, and neuronal circuits most likely process information differe...

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or fro...