{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:29:09Z","timestamp":1791930549288,"version":"4.3.4"},"reference-count":104,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The central cholinergic system is an important player in the control of motor function, appetite, the reward system, attention, memory and learning. Its participation in neurological diseases (e.g., Alzheimer\u2019s and Parkinson\u2019s disease, epilepsy) and in psychiatric diseases (e.g., schizophrenia, depression) makes it a preferred study subject for drug development. The present review summarizes salient features of the central cholinergic synapses that will guide future studies. Cholinergic synapses are defined by the presence of choline acetyltransferase (ChAT), the vesicular ACh transporter (VAChT), the high-affinity choline transporter CHT-1 and the presence of PRiMA-coupled acetylcholinesterase (AChE). The firing frequency of cholinergic fibers is reflected in high-affinity choline uptake activity, which also responds to variations in ChAT, VAChT and AChE activities conferring considerable plasticity to cholinergic responses. The availability of glucose and choline can limit ACh synthesis and release under conditions of high ACh turnover. Future studies will focus on rapid methods to measure ACh release and a deeper understanding of cholinergic plasticity during development, aging and dementia.<\/jats:p>","DOI":"10.3390\/ijms26199670","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T14:18:28Z","timestamp":1759501108000},"page":"9670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Central Cholinergic Synapse: A Primer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6971-3381","authenticated-orcid":false,"given":"Jochen","family":"Klein","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, FB14, J. W. Goethe University of Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.neuron.2012.08.036","article-title":"Acetylcholine as a neuromodulator: Cholinergic signaling shapes nervous system function and behavior","volume":"76","author":"Picciotto","year":"2012","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41583-023-00677-x","article-title":"Basal forebrain cholinergic signaling: Development, connectivity and roles in cognition","volume":"24","author":"Ananth","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Karczmar, A.G. (2007). 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