Here we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice and in vivo preparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all animals. IntroductionAcetylcholine (ACh) is a critical neurotransmitter in all animals. Among invertebrates, it is the most prevalent excitatory transmitter in the brain, sensory ganglia, and frequently the neuromuscular junction (NMJ). Among vertebrates, only a minority of neurons release ACh, but these signals play varying key roles. For instance, ACh signals at the NMJ, in the autonomic nervous system, and in subsets of the central nervous system, particularly projections arising from the brainstem and basal forebrain. Other cholinergic neuron populations in the brain include striatal interneurons, the stria vascularis-medial habenula-interpeduncular nucleus pathway, and sparse, incompletely characterized cell types such as intrinsic cholinergic interneurons in cortex 1 and hippocampus 2 . ACh helps to regulate attention 3 and wakefulness 4 , and participates in memory formation and consolidation 5 . ACh is also an important transmitter in glia, and between the nervous and immune systems 6 .Acetylcholine is synthesized pre-synaptically from choline and acetyl-CoA by choline acetyltransferase (ChAT), then packaged into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). A key, partially understood aspect of cholinergic signaling is co-release with other neurotransmitters, including GABA, ATP, and glutamate 7,8 . To understand the role of co-release, one must measure ACh release alongside emerging measurements of other neurotransmitters.Acetylcholine receptors are among the most diverse neurotransmitter receptor families. Humans possess five muscarinic G protein-coupled receptors (GPCRs) for ACh (mAChRs) with diverse expression in the brain and smooth, cardiac, and skeletal muscle. Vertebrate nicotinic ACh receptors (nAChRs) are pentameric ligand-gated cation channels. Humans have a total of 17 nAChR subunit genes, in five classes: 10 a, 4 b, and one each of g, d, and e. nAChRs occur with many subunit combinations 9 , and others may be undiscovered. Invertebrates also have AChgated chloride channels. On neurons, receptors can be localized pre-, post-, and extrasynaptically, often with different isoforms in each place 10
A 58-year-old male presented to the Outpatients Department for a painless swelling of great toe of right foot, of six months duration. Physical examination revealed a well-defined, firm, fixed, swelling of 2x2 cms on the distal phalanx of great toe of right foot. X-ray of the mass showed a dense soft tissue mass, with no bone involvement. The same was excised and sent for a histopathological examination.Gross examination revealed a well-defined mass of 2x2 cms. Cut section showed a firm, whitish tumour with gelatinous and chalky white areas of calcification, which were covered by a piece of skin on one side [Table/ Fig-1].Microscopic examination showed structure of skin with a tumour in the dermis, which was arranged in lobules which were separated by fibrous septa [Table/ Fig-2,3]. There were islands of mature hyaline cartilage, myxoid areas and foci of granular calcification. Some of the chondrocytes showed atypical nuclei 4]. A histopathological diagnosis of an extraskeletal chondroma was made. DisCussionESC-Soft tissue chondroma is a rare benign cartilaginous tumour and nearly 80% of ESCs are found in the fingers and the rest is seen in hands, feet, toes and trunk [1][2][3][4][5]. Few cases are reported at rare sites like dura, larynx, pharynx, oral cavity, skin, fallopian tube and parotid gland [6][7][8][9][10][11][12]. Pathology Section aBstRaCtExtraskeletal Chondroma (ESC) is uncommon which occurs predominantly in hands and feet. It has a variable histology, with two thirds of the ESCs showing mature hyaline cartilage which is arranged in distinct lobules with fibrosis, or ossification, or myxoid areas and few showing immature patterns, with chondroblasts mimicking extraskeletal myxoid chondrosarcomas (ESMCSs). ESCs can recur but they never metastasize, whereas ESMCSs can metastasize, which require aggressive treatment.We are reporting a case of ESC which was located in the distal phalanx of right foot great toe in a 58-year-old male patient. The histopathology in our case showed features of ESC, with some foci showing myxoid stroma and few chondroblasts with atypical pleomorphic nuclei mimicking ESMCS. Hence, the case had to be carefully evaluated to exclude ESMCS and to make the diagnosis of ESC. The treatment was limited to simple excision of the tumour and extensive surgery and post operative radiotherapy were avoided.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.