Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition.
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.
Prado
Vania F
VF
Departamento de Bioquímica-Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil.
Martins-Silva
Cristina
C
de Castro
Braulio M
BM
Lima
Ricardo F
RF
Barros
Daniela M
DM
Amaral
Ernani
E
Ramsey
Amy J
AJ
Sotnikova
Tatyana D
TD
Ramirez
Maria R
MR
Kim
Hyung-Gun
HG
Rossato
Janine I
JI
Koenen
Janaina
J
Quan
Hui
H
Cota
Vinicius R
VR
Moraes
Marcio F D
MF
Gomez
Marcus V
MV
Guatimosim
Cristina
C
Wetsel
William C
WC
Kushmerick
Christopher
C
Pereira
Grace S
GS
Gainetdinov
Raul R
RR
Izquierdo
Ivan
I
Caron
Marc G
MG
Prado
Marco A M
MA
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
D012333:RNA, Messenger; D050494:Vesicular Acetylcholine Transport Proteins; D000109:Acetylcholine