Neural oscillations arising from a linear current with negative conductance
Creators: name: Guan, Yinzheng
Publisher: name: No Publisher Supplied
Year: 2015

description: Slow oscillations underlying neuronal bursting commonly involve a regenerative inward ionic current with a nonlinear inverted bell-shape IV curve. In the crab pyloric central pattern generator (CPGs), multiple peptidergic modulatory inputs activate the regenerative inward current IMI in several pyloric neurons, which is critical for the generation of neuronal oscillations. Our recent work suggests that the contribution of such regenerative currents to the production of oscillations is limited to the region of the IV curve in which the current exhibits a linear negative-slope conductance (INL). When INL is introduced with dynamic clamp in the pyloric pacemaker PD neurons, it can recover oscillations, even when the neuron is isolated by TTX(Bose, Golowasch, Guan, &amp; Nadim, 2014) . However, it is unknown whether other pyloric neurons can produce oscillations in the presence of INL and, if not, what factors determine the ability of INL to produce them.  We examined whether, in the presence of TTX, INL is sufficient for producing slow oscillations in synaptically-isolated pyloric neurons. We found that the pyloric dilator PD neuron can produce INL-induced oscillations in a range of gNL (40-300 nS) and ENL (-15 to +15 rel. to Erest) values. The oscillation cycle period and amplitude decline with |gNL| and ENL. In contrast to the pyloric dilator (PD) neuron, even when gNL and ENL were varied in a large range, none of the follower pyloric neuron types pyloric constrictor (PY) (0/6), lateral pyloric (LP) (1/8), inferior cardiac (IC) (0/3), ventral dilator (VD) (0/3), lateral posterior gastric (LPG) (0/3) could produce slow oscillations with INL. We explored what factors may oppose the expression of oscillations in LP neurons in the presence of INL. Our previous modeling work suggests that INL-induced oscillations depend on a balance between INL and the voltage-gated outward currents (Bose et al., 2014). We therefore compared the outward currents in the PD and LP, PD and VD neurons. We found that the LP and VD neurons has a significantly larger high-threshold K current (IHTK: delayed rectifier and Ca2+-dep. K+ currents) than PD (20% larger at 0 mV), and that PD has a larger IA than LP (45% larger at 0 mV).   We thus examined whether changing the levels of IHTK and IA would affect the ability of PD or LP and VD to oscillate with INL. We found that LP and VD can oscillate with INL by reducing IHTK using TEA (N=4). However, in the presence of the 4AP we find that IA does not contribute to PD oscillation in INL (N=3). We conclude that interaction of INL with a slow voltage-gated outward current, is potentially leading to the generation of neuronal oscillations: these neurons are tuned  to express their currents levels in a way that fit in such an oscillatory range if they have the oscillatory properties.    This study has very important scientific value because it: 1. Contribute to understanding the role that leak currents –INL play in the transition from non-oscillatory to oscillatory activity. 2. Allows us to assess and define the intrinsic properties of different pyloric neurons. 3. Helps us to understand how a linear leak current INL can mimic a nonlinear regenerative current IMI to recover oscillatory activity.