title: Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition.
abstract: An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetically altered strain of mice with reduced expression of this transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65% decrease in VAChT protein expression, respectively. VAChT deficiency alters synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear normal in that respect and could be used for analysis of central cholinergic function. Behavioral analyses revealed that aversive learning and memory are not altered in mutant mice; however, performance in cognitive tasks involving object and social recognition is severely impaired. These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system.
authors.affiliation: Departamento de Bioquímica-Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.forename: Cristina
authors.initials: C
authors.lastname: Martins-Silva
authors.forename: Braulio M
authors.initials: BM
authors.lastname: de Castro
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Lima
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Barros
authors.forename: Ernani
authors.initials: E
authors.lastname: Amaral
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Ramsey
authors.forename: Tatyana D
authors.initials: TD
authors.lastname: Sotnikova
authors.forename: Maria R
authors.initials: MR
authors.lastname: Ramirez
authors.forename: Hyung-Gun
authors.initials: HG
authors.lastname: Kim
authors.forename: Janine I
authors.initials: JI
authors.lastname: Rossato
authors.forename: Janaina
authors.initials: J
authors.lastname: Koenen
authors.forename: Hui
authors.initials: H
authors.lastname: Quan
authors.forename: Vinicius R
authors.initials: VR
authors.lastname: Cota
authors.forename: Marcio F D
authors.initials: MF
authors.lastname: Moraes
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Gomez
authors.forename: Cristina
authors.initials: C
authors.lastname: Guatimosim
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.forename: Christopher
authors.initials: C
authors.lastname: Kushmerick
authors.forename: Grace S
authors.initials: GS
authors.lastname: Pereira
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
authors.forename: Ivan
authors.initials: I
authors.lastname: Izquierdo
authors.forename: Marc G
authors.initials: MG
authors.lastname: Caron
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
mesh_terms: D000109:Acetylcholine / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020511:Neuromuscular Junction Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D021641:Recognition, Psychology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D050494:Vesicular Acetylcholine Transport Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D050494:Vesicular Acetylcholine Transport Proteins; D000109:Acetylcholine