PT  - JOURNAL ARTICLE
AU  - Jorge Golowasch
AU  - Amitabha Bose
AU  - Yinzheng Guan
AU  - Dalia Salloum
AU  - Andrea Roeser
AU  - Farzan Nadim
TI  - A balance of outward and linear inward ionic currents is required for the generation of slow wave oscillations
AID  - 10.1101/136887
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 136887
4099  - http://biorxiv.org/content/early/2017/05/11/136887.short
4100  - http://biorxiv.org/content/early/2017/05/11/136887.full
AB  - Regenerative inward currents help produce slow oscillations through a negative-slope conductance region of their current-voltage relationship that is well approximated by a linear negative conductance. We used dynamic clamp injections of a linear current with this conductance, INL, to explore why some neurons can generate intrinsic slow oscillations whereas others cannot. We addressed this question, in synaptically isolated neurons of the crab Cancer borealis, after blocking action potentials. The pyloric network consists of distinct pacemaker group and follower neurons, all of which express the same complement of ionic currents. When the pyloric dilator (PD) neuron, a member of the pacemaker group, was injected with INL using dynamic clamp, it consistently produced slow oscillations. In contrast, the lateral pyloric (LP) or ventral pyloric (VD) follower neurons, failed to oscillate with INL. To understand these distinct behaviors, we compared outward current levels of PD, LP and VD neurons. We found that LP and VD neurons had significantly larger high-threshold potassium currents (IHTK) than PD, and LP had lower transient potassium current, IA. Reducing IHTK pharmacologically enabled both LP and VD neurons to produce oscillations with INL, whereas modifying IA levels did not affect INL-induced oscillations. Using phase-plane and bifurcation analysis of a simplified model cell, we demonstrate that large levels of IHTK can block INL-induced oscillatory activity, whereas generation of oscillations is almost independent of IA levels. These results demonstrate the importance of a balance between inward pacemaking currents and high-threshold K+current levels in determining slow oscillatory activity.