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Biophysical conditions triggering depolarization block in excitatory neurons.
Tobiáš, Marek ; Berling, David Maximilian (advisor) ; Korvasová, Karolína (referee)
Optogenetics is an increasingly popular neuronal stimulation technique used for study- ing neural circuits and controlling brain activity. However, when applied without suffi- cient knowledge, it can cause unintentional silencing of the targeted neurons by inducing a state termed depolarization block (DpB), in which neurons cease to fire action poten- tials. The susceptibility to silencing is not consistent among neurons, and the relationship between their biophysical properties and their vulnerability to DpB remains poorly un- derstood. In this thesis, we investigate how the densities of voltage-gated sodium (Nav) and potassium (Kv) channels, which are known to govern DpB dynamics, influence the neuron's ability to resist this phenomenon. We also examine the impact of neuronal size on DpB susceptibility. Using a computational model of a layer V pyramidal neuron, which we simplify to a single compartment to represent the behavior of a generic excita- tory neuron, we introduce an automatic classifier consistently identifying DpB through voltage trace analysis. This allows us to systematically assess the influence of varying Nav or Kv channel densities in the neuron's membrane. We discover that increasing these densities enhances the neuron's resistance to DpB. Contrary to previous studies, neu- ronal size...
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