A Brain without Brakes: Reduced Inhibition Is Associated with Enhanced but Dysregulated Plasticity in the Aged Rat Auditory Cortex.
A Brain without Brakes: Reduced Inhibition Is Associated with Enhanced but Dysregulated Plasticity in the Aged Rat Auditory Cortex.
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DOI：
10.1523/eneuro.0051-18.2018
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发表时间：
2018-07
期刊：
影响因子：
3.4
通讯作者：
de Villers-Sidani E
中科院分区：
文献类型：
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作者：
Cisneros-Franco JM;Ouellet L;Kamal B;de Villers-Sidani E
在称为可塑性关键期（CP）的早期发育窗口期间，感觉输入的质量和数量的被动改变足以引起皮质感觉表征的深刻且持久的扭曲。随着 CP 的关闭，这些表征得以稳定，这一过程需要抑制网络的成熟并在皮质中维持足够的 GABA 能张力。然而，在人类和啮齿类动物中，皮质抑制随着年龄的增长而逐渐减弱，这增加了老年人可塑性调节可能发生改变的可能性。在这里，我们测试了这样的假设：衰老会导致大鼠初级听觉皮层感觉表征的不稳定和适应不良的可塑性失调（A1）。与这个想法一致，我们发现被动音暴露足以扭曲老年大鼠 A1 区的频率调谐，但不会扭曲年轻成年大鼠的频率调谐。然而，我们还发现这些被动扭曲迅速衰减，表明老化皮层中 A1 调谐的持续不稳定。这些变化与皮质中 GABA 神经递质浓度的降低以及小白蛋白和神经周围净表达的减少有关。最后，我们表明，人为地增加老化 A1 中的 GABA 色调足以恢复表征稳定性并提高学习保留率。
During early developmental windows known as critical periods (CPs) of plasticity, passive alterations in the quality and quantity of sensory inputs are sufficient to induce profound and long-lasting distortions in cortical sensory representations. With CP closure, those representations are stabilized, a process requiring the maturation of inhibitory networks and the maintenance of sufficient GABAergic tone in the cortex. In humans and rodents, however, cortical inhibition progressively decreases with advancing age, raising the possibility that the regulation of plasticity could be altered in older individuals. Here we tested the hypothesis that aging results in a destabilization of sensory representations and maladaptive dysregulated plasticity in the rat primary auditory cortex (A1). Consistent with this idea, we found that passive tone exposure is sufficient to distort frequency tuning in the A1 of older but not younger adult rats. However, we also found that these passive distortions decayed rapidly, indicating an ongoing instability of A1 tuning in the aging cortex. These changes were associated with a decrease in GABA neurotransmitter concentration and a reduction in parvalbumin and perineuronal net expression in the cortex. Finally, we show that artificially increasing GABA tone in the aging A1 is sufficient to restore representational stability and improve the retention of learning.