Maturation of GABAergic inhibition promotes strengthening of temporally coherent inputs among convergent pathways.
Maturation of GABAergic inhibition promotes strengthening of temporally coherent inputs among convergent pathways.
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DOI：
10.1371/journal.pcbi.1000797
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发表时间：
2010-06-03
影响因子：
4.3
通讯作者：
Huang ZJ
中科院分区：
文献类型：
--
作者：
Kuhlman SJ;Lu J;Lazarus MS;Huang ZJ
尖峰时间依赖可塑性（STDP）是赫布可塑性的一种形式，具有内在的稳定性。GABA能抑制是否以及如何影响STDP尚不清楚。使用由STDP可修改的收敛输入驱动的模型神经元，我们确定足够水平的抑制对于确保突触输入的时间相干性（突触前尖峰时间之间的相关性）而不是通路内的输入的初始强度或数量控制突触后尖峰定时至关重要。抑制通过优先降低突触功效，输入引起突触后动作电位的能力，不太连贯的输入发挥这种作用。在视觉皮层切片中，抑制有效地降低了突触的功效，在年龄期间，但不是之前的关键时期的眼优势（OD）可塑性。全细胞记录显示，在关键期内，从小白蛋白阳性（Pv+）中间神经元到锥体神经元的单一IPSC的振幅增加，而突触衰减时间常数减小。此外，Pv+中间神经元的内在特性成熟，导致瞬时放电率增加。我们的研究结果表明，成熟的抑制在视觉皮层，确保时间上连贯的输入（例如，那些从单眼剥夺期间睁开的眼睛）控制双眼神经元的突触后锋电位时间，一个先决条件的Hebbian机制，以诱导OD可塑性。有证据表明，抑制的成熟是需要可塑性的发展进行在视觉皮层。然而，增加抑制促进可塑性的机制尚不清楚。在这里，我们的特点是成熟的突触和内在的离子特性的小清蛋白阳性interneurons，一个突出的亚型抑制性神经元在皮层。我们使用一个简单的整合-激发模型来模拟抑制成熟对联想可塑性规则的影响。我们模拟了两条输入通路，它们汇聚到单个突触后神经元上。活动的时间模式的构建不同的两个途径：一个途径代表视觉驱动的活动，而另一个途径代表感官剥夺的活动。在成熟的神经回路中，突触后细胞可以选择感觉驱动的输入而不是剥夺的输入，即使在剥夺的输入在突触大小或数量上具有初始优势的情况下。我们证明，成熟的抑制需要突触后细胞适当地选择感觉驱动的活动模式时，挑战对手的途径更大的尺寸。这些结果概述了一种机制，通过这种机制，抑制的成熟可以促进年轻人的可塑性，这是一个以提高学习能力为特征的发展时期。
Spike-timing-dependent plasticity (STDP), a form of Hebbian plasticity, is inherently stabilizing. Whether and how GABAergic inhibition influences STDP is not well understood. Using a model neuron driven by converging inputs modifiable by STDP, we determined that a sufficient level of inhibition was critical to ensure that temporal coherence (correlation among presynaptic spike times) of synaptic inputs, rather than initial strength or number of inputs within a pathway, controlled postsynaptic spike timing. Inhibition exerted this effect by preferentially reducing synaptic efficacy, the ability of inputs to evoke postsynaptic action potentials, of the less coherent inputs. In visual cortical slices, inhibition potently reduced synaptic efficacy at ages during but not before the critical period of ocular dominance (OD) plasticity. Whole-cell recordings revealed that the amplitude of unitary IPSCs from parvalbumin positive (Pv+) interneurons to pyramidal neurons increased during the critical period, while the synaptic decay time-constant decreased. In addition, intrinsic properties of Pv+ interneurons matured, resulting in an increase in instantaneous firing rate. Our results suggest that maturation of inhibition in visual cortex ensures that the temporally coherent inputs (e.g. those from the open eye during monocular deprivation) control postsynaptic spike times of binocular neurons, a prerequisite for Hebbian mechanisms to induce OD plasticity. Evidence suggests that maturation of inhibition is required for the development of plasticity to proceed in the visual cortex. However, the mechanisms by which increased inhibition promotes plasticity are not clear. Here we characterized the maturation of synaptic and intrinsic ionic properties of parvalbumin-positive interneurons, a prominent subtype of inhibitory neuron in the cortex. We used a simple integrate-and-fire model to simulate the influence of maturation of inhibition on associative plasticity rules. We simulated two input pathways that converged onto a single postsynaptic neuron. The temporal pattern of activity was constructed differently for the two pathways: one pathway represented visually-driven activity, while the other pathway represented sensory-deprived activity. In mature circuits it is established that postsynaptic cells can select for sensory-driven inputs over deprived inputs, even in the case that deprived inputs have an initial advantage in synaptic size or number. We demonstrated that maturation of inhibition was required for postsynaptic cells to appropriately select sensory-driven patterns of activity when challenged with an opponent pathway of greater size. These results outline a mechanism by which maturation of inhibition can promote plasticity in the young, a period of development that is characterized by heightened learning.
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影响因子：
56.9
作者：
Fu, YX;Djupsund, K;Dan, Y
通讯作者：
Dan, Y
影响因子：
2.5
作者：
Aizenman, CD;Linden, DJ
通讯作者：
Linden, DJ
DOI：
10.1073/pnas.96.3.1083
发表时间：
1999-02-02
影响因子：
11.1
作者：
Blais, BS;Shouval, HZ;Cooper, LN
通讯作者：
Cooper, LN
影响因子：
9.8
作者：
通讯作者：
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影响因子：
16.2
作者：
Frenkel, MY;Bear, MF
通讯作者：
Bear, MF