Fast activation of feedforward inhibitory neurons from thalamic input and its relevance to the regulation of spike sequences in the barrel cortex
Fast activation of feedforward inhibitory neurons from thalamic input and its relevance to the regulation of spike sequences in the barrel cortex
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DOI：
10.1113/jphysiol.2010.188177
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发表时间：
2010-08-01
影响因子：
5.5
通讯作者：
Ohshima, Minoru
中科院分区：
文献类型：
--
作者：
Kimura, Fumitaka;Itami, Chiaki;Ohshima, Minoru
丘脑皮质传入同时支配兴奋性和抑制性细胞，后者反过来产生双突触前馈抑制，从而在皮层细胞中产生快速的兴奋-抑制序列。由于这种抑制是双突触的，兴奋-抑制序列的时延可能类似于2-3ms，而通常只短至略高于1ms；这种快速IPSP的机制和功能尚不完全清楚。在这里，我们表明丘脑抑制神经元的激活先于兴奋性神经元，这是由于支配抑制细胞的丘脑轴突的传导速度增加。在发育上，这种潜伏期差异只有在出生后第二周结束后才能看到，在丘脑皮质传入神经髓化完成之前。此外，破坏髓鞘并不能消除潜伏期的差异。相反，支配抑制性细胞的轴突的阈值一直较低，这表明它们的直径更大，这可能是差异传导速度的基础。由于来自丘脑的GABA能神经元的快速激活不仅可以抑制单突触的EPSP，而且可以使双突触的ISPS先于双突触的EPSP，这种抑制理论上使得丘脑驱动的单突触和双突触的EPSP能够在时间上分离，导致L4领先L2/3的棘波序列。通过同时记录L4和L2/3细胞，我们发现抑制IPSPs可以导致尖峰序列的恶化。因此，从出生后第二周开始，通过激活GABA能神经元而不是来自丘脑的兴奋性神经元，对突触后细胞的快速前馈双突触抑制可能在建立L4前导L2/3细胞的棘波序列中发挥作用。
Thalamocortical afferents innervate both excitatory and inhibitory cells, the latter in turn producing disynaptic feedforward inhibition, thus creating fast excitation-inhibition sequences in the cortical cells. Since this inhibition is disynaptic, the time lag of the excitation-inhibition sequence could be similar to 2-3 ms, while it is often as short as only slightly above 1 ms; the mechanism and function of such fast IPSPs are not fully understood. Here we show that thalamic activation of inhibitory neurons precedes that of excitatory neurons, due to increased conduction velocity of thalamic axons innervating inhibitory cells. Developmentally, such latency differences were seen only after the end of the second postnatal week, prior to the completion of myelination of the thalamocortical afferent. Furthermore, destroying myelination failed to extinguish the latency difference. Instead, axons innervating inhibitory cells had consistently lower threshold, indicating they had larger diameter, which is likely to underlie the differential conduction velocity. Since faster activation of GABAergic neurons from the thalamus can not only curtail monosynaptic EPSPs but also make disynaptic ISPSs precede disynaptic EPSPs, such suppression theoretically enables a temporal separation of thalamically driven mono- and disynaptic EPSPs, resulting in spike sequences of 'L4 leading L2/3'. By recording L4 and L2/3 cells simultaneously, we found that suppression of IPSPs could lead to deterioration of spike sequences. Thus, from the end of the second postnatal week, by activating GABAergic neurons prior to excitatory neurons from the thalamus, fast feedforward disynaptic suppression on postsynaptic cells may play a role in establishing the spike sequences of 'L4 leading L2/3 cells'.