Golowasch Jorge, Bose Amitabha, Guan Yinzheng, Salloum Dalia, Roeser Andrea, Nadim Farzan
Federated Department of Biological Sciences, New Jersey Institute of Technology and Rutgers University, Newark, New Jersey; and
Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey.
J Neurophysiol. 2017 Aug 1;118(2):1092-1104. doi: 10.1152/jn.00240.2017. Epub 2017 May 24.
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, , to explore why some neurons can generate intrinsic slow oscillations whereas others cannot. We addressed this question in synaptically isolated neurons of the crab 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 with dynamic clamp, it consistently produced slow oscillations. In contrast, all follower neurons failed to oscillate with 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 () than PD and LP had lower-transient potassium current (). Reducing pharmacologically enabled both LP and VD neurons to produce -induced oscillations, whereas modifying levels did not affect -induced oscillations. Using phase-plane and bifurcation analysis of a simplified model cell, we demonstrate that large levels of can block -induced oscillatory activity whereas generation of oscillations is almost independent of 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. 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.
再生内向电流通过其电流-电压关系的负斜率电导区域帮助产生缓慢振荡，该区域可通过线性负电导很好地近似。我们使用动态钳位注入具有这种电导的线性电流，以探究为什么一些神经元能够产生内在的缓慢振荡而其他神经元则不能。我们在阻断动作电位后，对螃蟹的突触隔离神经元解决了这个问题。幽门网络由不同的起搏器和跟随神经元组成，所有这些神经元都表达相同的离子电流组合。当使用动态钳位向起搏器组的成员幽门扩张器（PD）神经元注入时，它持续产生缓慢振荡。相比之下，所有跟随神经元在注入时都未能振荡。为了理解这些不同的行为，我们将PD的外向电流水平与跟随神经元外侧幽门（LP）和腹侧幽门（VD）神经元的外向电流水平进行了比较。我们发现LP和VD神经元具有比PD显著更大的高阈值钾电流，并且LP具有较低的瞬时钾电流。药理学上降低使LP和VD神经元都能产生诱导振荡，而改变水平并不影响诱导振荡。使用简化模型细胞的相平面和分岔分析，我们证明高水平的可以阻断诱导的振荡活动，而振荡的产生几乎与水平无关。这些结果证明了内向起搏电流和高阈值K电流水平之间的平衡在决定缓慢振荡活动中的普遍重要性。起搏器神经元产生的节律性活动需要至少一种内向电流和一种外向电流的激活。我们之前已经表明内向电流可以是线性电流（具有负电导）。使用这种简单机制，我们在此证明内向电流电导必须与外向电流电导相对平衡才能产生振荡活动。令人惊讶的是，过量的外向电导完全排除了实现这种平衡的可能性。
