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Abstract
Neuronal activity is mediated through changes in the probability of stochastic transitions between open and closed states of ion channels. While differences in morphology define neuronal cell types and may underlie neurological disorders, very little is known about influences of stochastic ion channel gating in neurons with complex morphology. We introduce and validate new computational tools that enable efficient generation and simulation of models containing stochastic ion channels distributed across dendritic and axonal membranes. Comparison of five morphologically distinct neuronal cell types reveals that when all simulated neurons contain identical densities of stochastic ion channels, the amplitude of stochastic membrane potential fluctuations differs between cell types and depends on sub-cellular location. For typical neurons, the amplitude of membrane potential fluctuations depends on channel kinetics as well as open probability. Using a detailed model of a hippocampal CA1 pyramidal neuron, we show that when intrinsic ion channels gate stochastically, the probability of initiation of dendritic or somatic spikes by dendritic synaptic input varies continuously between zero and one, whereas when ion channels gate deterministically, the probability is either zero or one. At physiological firing rates, stochastic gating of dendritic ion channels almost completely accounts for probabilistic somatic and dendritic spikes generated by the fully stochastic model. These results suggest that the consequences of stochastic ion channel gating differ globally between neuronal cell-types and locally between neuronal compartments. Whereas dendritic neurons are often assumed to behave deterministically, our simulations suggest that a direct consequence of stochastic gating of intrinsic ion channels is that spike output may instead be a probabilistic function of patterns of synaptic input to dendrites.
Highlights
The appropriate level of physical detail required to understand how complex processes such as cognition and behavior emerge from more simple biological structures is unclear [1,2]
While cable theory suggests that fluctuations of this kind might be important in fine structures such as axons and dendrites [21], we know very little about how neuronal morphology and stochastic gating of ion channels interact to determine how neurons respond to synaptic input
We show that the functional impact of stochastic ion channel gating depends on neuronal morphology and as a result differs between neuronal cell types
Summary
The appropriate level of physical detail required to understand how complex processes such as cognition and behavior emerge from more simple biological structures is unclear [1,2]. While the assumption that transitions between open and closed states of ion channels can be treated as a deterministic process may be sufficient for some purposes, recent evidence suggests that stochastic transitions between the states of individual ion channels could influence computations carried out by neurons [10,11,12,13,14,15,16,17]. While cable theory suggests that fluctuations of this kind might be important in fine structures such as axons and dendrites [21], we know very little about how neuronal morphology and stochastic gating of ion channels interact to determine how neurons respond to synaptic input. Given the difficulty of reducing detailed morphological models to simple analytical forms that could incorporate stochastic gating of individual ion channels [22], experimentally constrained numerical simulations will be important to enable these issues to be explored systematically
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