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Medial septal dysfunction by A beta-induced KCNQ channel-block in glutamatergic neurons
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
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2012 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 9, 2046-2061 p.Article in journal (Refereed) Published
Abstract [en]

Amyloid beta (A beta) peptides play a central role in the pathophysiology of Alzheimer's disease (AD). The cellular mechanisms underlying A beta toxicity, however, are poorly understood. Here we show that A beta 25-35 and A beta 1-40 acutely and differentially affect the characteristics of 3 classes of medial septum (MS) neurons in mice. In glutamatergic neurons A beta increases firing frequency and blocks the A-and the M-current (I-A and I-M, respectively). While the I-A block is similar in other MS neuron classes, the block of I-M is specific to glutamatergic neurons. I-M block and a simulated A beta block mimic the A beta-induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. A beta increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta firing coherence. Our results demonstrate that A beta-induced dysfunction of glutamatergic neurons via I-M decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer's disease.

Place, publisher, year, edition, pages
2012. Vol. 33, no 9, 2046-2061 p.
Keyword [en]
Amyloid beta peptide, Medial septum, Theta oscillations, Glutamatergic neurons, Cholinergic neurons, GABAergic neurons, M-current, A-current
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-181397DOI: 10.1016/j.neurobiolaging.2011.07.013ISI: 000306994600018OAI: oai:DiVA.org:uu-181397DiVA: diva2:557688
Available from: 2012-09-28 Created: 2012-09-24 Last updated: 2012-09-28Bibliographically approved

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Leão, Richardson N.
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