Linked Life Data

15537882

Source:http://linkedlifedata.com/resource/pubmed/id/15537882

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2004-11-11
pubmed:abstractText
Muscarinic acetylcholine receptors are known to play key roles in facilitating cognitive processes. However, the specific roles of the individual muscarinic receptor subtypes (M1-M5) in learning and memory are not well understood at present. In the present study, we used wild-type (M2+/+) and M2 receptor-deficient (M2-/-) mice to examine the potential role of M2 receptors in learning and memory and hippocampal synaptic plasticity. M2-/- mice showed significant deficits in behavioral flexibility and working memory in the Barnes circular maze and the T-maze delayed alternation tests, respectively. The behavioral deficits of M2-/- mice were associated with profound changes in neuronal plasticity studied at the Schaffer-CA1 synapse of hippocampal slices. Strikingly, short-term potentiation (STP) was abolished, and long-term potentiation (LTP) was drastically reduced after high-frequency stimulation of M2-/- hippocampi. Treatment of M2-/- hippocampal slices with the GABA(A) receptor antagonist, bicuculline, restored STP and significantly increased LTP. Whole-cell recordings from CA1 pyramidal cells demonstrated a much stronger disinhibition of GABAergic than glutamatergic transmission in M2-/- hippocampi, which was particularly prominent during stimulus trains. Increased strength of GABAergic inhibition is thus a likely mechanism underlying the impaired synaptic plasticity observed with M2-/- hippocampi. Moreover, the persistent enhancement of excitatory synaptic transmission in CA1 pyramidal cells induced by the transient application of a low concentration of a muscarinic agonist (referred to as LTP(m)) was totally abolished in M2-/- mice. Because impaired muscarinic cholinergic neurotransmission is associated with Alzheimer's disease and normal aging processes, these findings should be of considerable therapeutic relevance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10117-27
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15537882-Amnesia, pubmed-meshheading:15537882-Animals, pubmed-meshheading:15537882-Behavior, Animal, pubmed-meshheading:15537882-Bicuculline, pubmed-meshheading:15537882-Carbachol, pubmed-meshheading:15537882-Excitatory Postsynaptic Potentials, pubmed-meshheading:15537882-Gallamine Triethiodide, pubmed-meshheading:15537882-Hippocampus, pubmed-meshheading:15537882-Long-Term Potentiation, pubmed-meshheading:15537882-Male, pubmed-meshheading:15537882-Maze Learning, pubmed-meshheading:15537882-Memory, pubmed-meshheading:15537882-Mice, pubmed-meshheading:15537882-Mice, Knockout, pubmed-meshheading:15537882-Muscarinic Agonists, pubmed-meshheading:15537882-Neuronal Plasticity, pubmed-meshheading:15537882-Patch-Clamp Techniques, pubmed-meshheading:15537882-Pyramidal Cells, pubmed-meshheading:15537882-Receptor, Muscarinic M2, pubmed-meshheading:15537882-Receptors, GABA-A
pubmed:year
2004
pubmed:articleTitle
M2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity.
pubmed:affiliation
Department of Physiology, University of Munich, D-80336 Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't