Navegando por Autor "Lotta Borgius"

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Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons
(2011-07) Leão, Richardson Naves; Luis V. Colom; Lotta Borgius; Ole Kiehn; André Fisahn
Amyloid (A ) peptides play a central role in the pathophysiology of Alzheimer’s disease (AD). The cellular mechanisms underlying A toxicity, however, are poorly understood. Here we show that A 25-35 and A 1-40 acutely and differentially affect the characteristics of 3 classes of medial septum (MS) neurons in mice. In glutamatergic neurons A increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated A block mimic the A -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 increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta firing coherence. Our results demonstrate that A -induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer’s disease.

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