Document Detail

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation.
MedLine Citation:
PMID:  23045697     Owner:  NLM     Status:  MEDLINE    
Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.
Amanda C Martyn; Xavier De Jaeger; Ana C Magalhães; Rohit Kesarwani; Daniela F Gonçalves; Sanda Raulic; Monica S Guzman; Michael F Jackson; Ivan Izquierdo; John F Macdonald; Marco A M Prado; Vania F Prado
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17651-6     Citation Subset:  IM    
Molecular Brain Research Group, Robarts Research Institute, and Department of Anatomy and Cell Biology and Physiology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada N6A 5K8.
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MeSH Terms
Behavior, Animal*
Blotting, Western
Fluorescent Antibody Technique
Long-Term Potentiation*
Mice, Knockout
Neuronal Plasticity
Polymerase Chain Reaction
Prosencephalon / metabolism*
Vesicular Acetylcholine Transport Proteins / metabolism*
Reg. No./Substance:
0/Vesicular Acetylcholine Transport Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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