Parallel regulation of a modulator-activated current via distinct dynamics underlies comodulation of motor circuit output.
Parallel regulation of a modulator-activated current via distinct dynamics underlies comodulation of motor circuit output.
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DOI：
10.1523/jneurosci.3079-09.2009
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发表时间：
2009-09-30
期刊：
影响因子：
--
通讯作者：
Nusbaum MP
中科院分区：
文献类型：
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作者：
DeLong ND;Kirby MS;Blitz DM;Nusbaum MP
在大多数系统中，神经元网络共调节的细胞机制尚未阐明。我们正在通过确定一种肽激素，甲壳类心脏活性肽（CCAP）调节螃蟹口胃神经节中由投射神经元MCN1驱动的双相（伸/收）胃磨（咀嚼）节律的机制来解决这个问题。MCN1分别通过缓慢的肽能（CabTRP Ia）和快速的gaba能激发相互抑制的中枢模式产生神经元LG（拉伸）和Int1（收缩）来激活这种节律。MCN1突触传递仅限于收缩期，因为LG在拉伸期间抑制MCN1。浸浴时使用的CCAP也会刺激LG和Int1，但会选择性地延长延长时间。在这里，我们使用计算建模和动态箝位操作来确定CCAP通过激活与mcn1释放的CabTRP Ia相同的调制器激活的LG内电流（IMI）来延长胃磨量角器（LG）相位并维持牵开器（Int1）相位持续时间。然而，ccap激活电流（IMI-CCAP）和mcn1激活电流（IMI-MCN1）在延长过程中表现出不同的时间过程。这种区别是由于IMI-CCAP仅受突触后电压调节，而IMI-MCN1也受MCN1的LG突触前抑制的调节。因此，在没有CCAP的情况下，LG中IMI-MCN1积累和反馈抑制介导的衰减的时间过程分别决定了收缩和拉伸的持续时间。随着IMI-CCAP的持续存在，反馈抑制的影响减弱，延长了牵伸，维持了牵伸持续时间。因此，节律性运动活动的共调制可以通过单个电压相关电流的不同动态产生收敛激活。
The cellular mechanisms underlying co-modulation of neuronal networks are not elucidated in most systems. We are addressing this issue by determining the mechanism by which a peptide hormone, crustacean cardioactive peptide (CCAP), modulates the biphasic (protraction/retraction) gastric mill (chewing) rhythm driven by the projection neuron MCN1 in the crab stomatogastric ganglion. MCN1 activates this rhythm by slow peptidergic (CabTRP Ia) and fast GABAergic excitation of the reciprocally inhibitory central pattern generator neurons LG (protraction) and Int1 (retraction), respectively. MCN1 synaptic transmission is limited to the retraction phase, because LG inhibits MCN1 during protraction. Bath-applied CCAP also excites both LG and Int1, but selectively prolongs protraction. Here, we use computational modeling and dynamic clamp manipulations to establish that CCAP prolongs the gastric mill protractor (LG) phase and maintains the retractor (Int1) phase duration by activating the same modulator-activated inward current (IMI) in LG as MCN1-released CabTRP Ia. However, the CCAP-activated current (IMI-CCAP) and MCN1-activated current (IMI-MCN1) exhibit distinct time courses in LG during protraction. This distinction results from IMI-CCAP being regulated only by postsynaptic voltage, whereas IMI-MCN1 is also regulated by LG presynaptic inhibition of MCN1. Hence, without CCAP, retraction and protraction duration are determined by the time course of IMI-MCN1 build-up and feedback inhibition-mediated decay, respectively, in LG. With IMI-CCAP continually present, the impact of the feedback inhibition is reduced, prolonging protraction and maintaining retraction duration. Thus, co-modulation of rhythmic motor activity can result from convergent activation, via distinct dynamics, of a single voltage-dependent current.