Publication Date:
2008-09-20
Description:
The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Busche, Marc Aurel -- Eichhoff, Gerhard -- Adelsberger, Helmuth -- Abramowski, Dorothee -- Wiederhold, Karl-Heinz -- Haass, Christian -- Staufenbiel, Matthias -- Konnerth, Arthur -- Garaschuk, Olga -- New York, N.Y. -- Science. 2008 Sep 19;321(5896):1686-9. doi: 10.1126/science.1162844.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Neurowissenschaften, Technische Universitat Munchen (TUM), 80802 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18802001" target="_blank"〉PubMed〈/a〉
Keywords:
Alzheimer Disease/*pathology/*physiopathology
;
Amyloid beta-Peptides/metabolism
;
Animals
;
Calcium/metabolism
;
Calcium Signaling
;
Cerebral Cortex/pathology/*physiopathology
;
*Disease Models, Animal
;
Maze Learning
;
Memory
;
Mice
;
Mice, Transgenic
;
Nerve Net/physiopathology
;
Neurons/*physiology
;
Peptide Fragments/metabolism
;
Plaque, Amyloid/chemistry/*pathology
;
Synapses/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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