Mice Deficient for the Vesicular Acetylcholine Transporter Are Myasthenic and Have Deficits in Object and Social Recognition

• Published in: Neuron (Cambridge, Mass.) Mass.), 2006-09, Vol.51 (5), p.601-612
• Main Authors: Prado, Vania F., Martins-Silva, Cristina, de Castro, Braulio M., Lima, Ricardo F., Barros, Daniela M., Amaral, Ernani, Ramsey, Amy J., Sotnikova, Tatyana D., Ramirez, Maria R., Kim, Hyung-Gun, Rossato, Janine I., Koenen, Janaina, Quan, Hui, Cota, Vinicius R., Moraes, Marcio F.D., Gomez, Marcus V., Guatimosim, Cristina, Wetsel, William C., Kushmerick, Christopher, Pereira, Grace S., Gainetdinov, Raul R., Izquierdo, Ivan, Caron, Marc G., Prado, Marco A.M.
• Format: Article
• Language: English
• Subjects: Acetylcholine - analysis; Acetylcholine - secretion; Alzheimer's disease; Animal cognition; Animals; Behavior; Blotting, Northern; Blotting, Southern; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brain Chemistry; Chromatography, High Pressure Liquid; Experiments; Female; Gene expression; Grants; Kinases; Male; Membrane Potentials - physiology; Mice; Mice, Transgenic; Microdialysis; MOLNEURO; Motor Activity - physiology; Neuromuscular Junction - metabolism; Neuromuscular Junction - pathology; Neuromuscular Junction - physiopathology; Neuromuscular Junction Diseases - etiology; Neuromuscular Junction Diseases - pathology; Neuromuscular Junction Diseases - physiopathology; Polymerase Chain Reaction; Proteins; Recognition (Psychology) - physiology; RNA, Messenger - analysis; Rodents; Spinal cord; Synaptic Transmission - physiology; SYSNEURO; Vesicular Acetylcholine Transport Proteins - deficiency; Vesicular Acetylcholine Transport Proteins - genetics
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2006.08.005

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.