A balance of outward and linear inward ionic currents is required for generation of slow-wave oscillations

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 such conductance, I_NL, 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 a distinct pacemaker 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 I_NL with dynamic clamp, it consistently produced slow oscillations. In contrast, all follower neurons failed to oscillate with I_NL. To understand these distinct behaviors, we compared outward current levels of PD with those of follower lateral pyloric (LP) and ventral pyloric (VD) neurons. We found that LP and VD neurons had significantly larger high-threshold potassium currents (I_HTK) than PD and LP had lower-transient potassium current (I_A). Reducing I_HTK pharmacologically enabled both LP and VD neurons to produce I_NL-induced oscillations, whereas modifying I_A levels did not affect I_NL-induced oscillations. Using phase-plane and bifurcation analysis of a simplified model cell, we demonstrate that large levels of I_HTK can block I_NL-induced oscillatory activity whereas generation of oscillations is almost independent of I_A levels. These results demonstrate the general importance of a balance between inward pacemaking currents and high-threshold K⁺ current levels in determining slow oscillatory activity.

NEW & NOTEWORTHY Pacemaker neuron-generated rhythmic activity requires the activation of at least one inward and one outward current. We have previously shown that the inward current can be a linear current (with negative conductance). Using this simple mechanism, here we demonstrate that the inward current conductance must be in relative balance with the outward current conductances to generate oscillatory activity. Surprisingly, an excess of outward conductances completely precludes the possibility of achieving such a balance.

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