RT Journal Article
SR Electronic
T1 Stochastic Calcium Mechanisms Cause Dendritic Calcium Spike Variability
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 15848
OP 15867
DO 10.1523/JNEUROSCI.1722-13.2013
VO 33
IS 40
A1 Anwar, Haroon
A1 Hepburn, Iain
A1 Nedelescu, Hermina
A1 Chen, Weiliang
A1 De Schutter, Erik
YR 2013
UL http://www.jneurosci.org/content/33/40/15848.abstract
AB Bursts of dendritic calcium spikes play an important role in excitability and synaptic plasticity in many types of neurons. In single Purkinje cells, spontaneous and synaptically evoked dendritic calcium bursts come in a variety of shapes with a variable number of spikes. The mechanisms causing this variability have never been investigated thoroughly. In this study, a detailed computational model using novel simulation routines is applied to identify the roles that stochastic ion channels, spatial arrangements of ion channels, and stochastic intracellular calcium have toward producing calcium burst variability. Consistent with experimental recordings from rats, strong variability in the burst shape is observed in simulations. This variability persists in large model sizes in contrast to models containing only voltage-gated channels, where variability reduces quickly with increase of system size. Phase plane analysis of Hodgkin-Huxley spikes and of calcium bursts identifies fluctuation in phase space around probabilistic phase boundaries as the mechanism determining the dependence of variability on model size. Stochastic calcium dynamics are the main cause of calcium burst fluctuations, specifically the calcium activation of mslo/BK-type and SK2 channels. Local variability of calcium concentration has a significant effect at larger model sizes. Simulations of both spontaneous and synaptically evoked calcium bursts in a reconstructed dendrite show, in addition, strong spatial and temporal variability of voltage and calcium, depending on morphological properties of the dendrite. Our findings suggest that stochastic intracellular calcium mechanisms play a crucial role in dendritic calcium spike generation and are therefore an essential consideration in studies of neuronal excitability and plasticity.