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ANC Seminar: Erik Fransén (KTH, Stockholm)

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What
  • ANC/DTC Seminar
When Jul 26, 2016
from 11:00 AM to 12:00 PM
Where IF 4.31/4.33
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A-type potassium currents in dendritic integration of high frequency input. Role in learning and in epilepsy.

 

Sharp-waves and gamma bouts are patterns of activity discussed in relation to learning and memory. Furthermore, patterns of even higher frequency, fast ripples/high frequency oscillations, are described in epileptic seizures with an hypersynchronous onset. In this presentation, we will discuss the potential role of A-type potassium currents (KA) originating from activation of Kv4.2 heteromeric channels in selective suppression of synaptic input of high frequency. In computational modeling of CA1 pyramidal neurons, we find that the selective suppression of KA increases when synaptic inputs are placed on oblique dendrites further out from the soma as well as radially further out. We further find that excitatory input from entorhinal cortex to the apikal tuft provides a modulatory influence reducing the capacity of KA to suppress synchronized activity. Conversely, inhibitory tuft input increases the suppression by KA. Moreover, using computational modeling
and optimization, we aimed at reversing the pathological characteristics of reduced KA current or altered channel gating observed in animal models of epilepsy and human patients respectively and restoring normal neural function by altering KA ion channel properties. We find that distinct subtype compositions of the auxiliary proteins Kv channel interacting proteins 1 (KChIP1) and dipeptidyl aminopeptidase-like protein 6 (DPP6) were able to restore KA conductance changes. Moreover, particular combinations of protein kinase C, calmodulin dependent protein kinase II, and arachidonic acid were also able to restore these changes as well as the channel pathology found in a patient with temporal lobe epilepsy.