Nonequilibrium Calcium Dynamics Regulate the Autonomous Firing Pattern of Rat Striatal Cholinergic Interneurons

Abstract

Striatal cholinergic interneurons discharge rhythmically in two patterns associated with different afterhyperpolarization timescales, each dictated by a different calcium-dependent potassium current. Single spiking depends on a medium-duration afterhyperpolarization (mAHP) generated by rapid SK currents that are associated with N-type calcium channels. Periodic bursting is driven by a delayed and slowly decaying afterhyperpolarization (sAHP) current associated with L-type channels. Using calcium imaging we show that the calcium transients underlying these currents exhibit two corresponding timescales throughout the somatodendritic tree. This result is not consistent with spatial compartmentalization of calcium entering through the two calcium channels and acting on the two potassium currents, or with differences in channel gating kinetics of the calcium dependent potassium currents. Instead, we show that nonequilibrium dynamics of calcium redistribution among cytoplasmic binding sites with different calcium binding kinetics can give rise to multiple timescales within the same cytoplasmic volume. The resulting independence of mAHP and sAHP currents allows cytoplasmic calcium to control two different and incompatible firing patterns (single spiking or bursting and pausing), depending on whether calcium influx is pulsatile or sustained. During irregular firing, calcium entry at both timescales can be detected, suggesting that an interaction between the medium and slow calcium-dependent afterhyperpolarizations may underlie this firing pattern.

Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing Dynamics in Gonadotropin-Releasing Hormone Neurons

“…In contrast, sI AHP-UCL had little or no effect upon burst structure but exerted a powerful restraining influence upon the timing of bursts. Recent studies have highlighted likely interactions between SK and sI AHP channels in the regulation of neuronal firing in the striatum and amygdala (Power and Sah, 2008;Goldberg et al, 2009). Although we find some evidence for interaction in terms of regulating IBI, burst dynamics are clearly dependent on only sI AHP-SK .…”

Biophysical basis of the phase response curve of subthalamic neurons with generalization to other cell types

“…Such a situation can arise if Ca 2ϩ entering the cell during an action potential cascades through a g is the maximal conductance, V H is the half-activation (or -inactivation) voltage for steady-state activation (inactivation), and V S is the slope factor specifying the steepness of the voltage dependence for Na ϩ , K ϩ delayed rectifier (KDR), persistent Na ϩ (NaP), Ca 2ϩ , small-conductance Ca 2ϩ -dependent K ϩ (SK), and leak conductances (see MATERIALS AND METHODS). series of Ca 2ϩ -binding molecules of varying Ca 2ϩ affinity and kinetics: Ca 2ϩ could initially interact with faster but lower affinity binding sites before being handed off to slower but higher affinity sites (Goldberg et al 2009). This suggests that a model that correctly accounts for Ca 2ϩ dynamics and SK activation in STN cells would be quite complicated.…”

The pathology roadmap in Parkinson disease

“…In contrast, most other relatively PD-resistant autonomous pacemakers in the brain express a high level of calcium binding proteins (e.g., ventral tegmental area neurons, Purkinje neurons, globus pallidus neurons, striatal cholinergic interneurons). 86,87 The expression of known calcium binding proteins in the autonomic nervous system and enteric nervous system varies from cell type to cell type. [88][89][90] In addition, SNc and locus coeruleus neurons allow significant amounts of calcium to enter during the period between spikes.…”