Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity.

Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity.
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DOI:
10.1038/nn.3004
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发表时间:
2011-12-18
影响因子:
25
通讯作者:
--
中科院分区:
医学1区
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--
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反复兴奋性回路在平衡有效性和稳定性方面面临着极大的挑战。我们记录了大鼠海马切片培养的CA3锥体神经元对,以表征长期不活动导致的复发突触的突触和回路水平的变化。慢性ttx治疗大大降低了连接的CA3-CA3神经元的百分比,但增强了剩余连接的强度;在量子大小不变的情况下,突触前释放概率急剧增加。突触功能沉默导致活动剥夺回路的连通性下降,而3D解剖分析显示脊柱或钮扣密度或总树突长度没有变化。这种沉默是由Cdk5活性增强引起的,可以通过罗斯科维汀急性抑制Cdk5来恢复。我们的研究结果表明,循环回路通过不均匀地重新分配突触前权重来适应慢性不活动,加强某些连接,同时沉默其他连接。这限制了突触的输出和输入,在保护网络稳定性的同时,在神经元集合的子集中保持信号的有效性。
Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic TTX-treatment greatly reduced the percentage of connected CA3-CA3 neurons but enhanced the strength of the remaining connections; presynaptic release probability sharply increased while quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas 3D anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while also protecting network stability.
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