Axon initial segment plasticity accompanies enhanced excitation of visual cortical neurons in aged rats.
Axon initial segment plasticity accompanies enhanced excitation of visual cortical neurons in aged rats.
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DOI：
10.1097/wnr.0000000000001145
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发表时间：
2018-12-12
期刊：
影响因子：
1.7
通讯作者：
Hua T
中科院分区：
文献类型：
--
作者：
Ding Y;Chen T;Wang Q;Yuan Y;Hua T
最近的研究表明，神经元的轴突起始段（AIS）的结构是高度可塑性的，以响应神经元活动的变化。视皮层神经元反应的年龄相关性增强是否与AIS的可塑性相结合尚不清楚。在此，我们比较了年轻成年和老年大鼠初级视皮层（V1）II/III层神经元AIS的长度和Nav1.6（动作电位（AP）起始的关键Na+离子通道）的分布，沿着AIS。在这项研究中，我们发现，老年大鼠的V1神经元比年轻大鼠的神经元表现出明显更高的自发活动和更强的视觉诱发反应。我们的研究结果表明，老年大鼠V1区Ⅱ/Ⅲ层神经元AIS的平均长度明显短于青年大鼠。此外，与年轻大鼠相比，老年大鼠中具有Nav1.6分布的AIS比例也显著降低，如AIS内平均Nav1.6免疫荧光光密度降低和AIS近端区域附近Nav1.6免疫荧光光密度的特异性降低所示。我们的研究结果表明，老化导致AIS缩短和Nav1.6 Na+离子通道分布沿着AIS减少，这伴随着神经元活性的增强。这种与年龄相关的形态可塑性可能通过减少AP启动期间的Na+离子进入来降低AP幅度，在膜电位恢复期间节省Na+离子泵消耗的ATP，从而平衡衰老过程中皮层神经元放电率增加所引起的能量消耗。
Recent studies have indicated that the structure of the axon initial segment (AIS) of neurons is highly plastic in response to changes in neuronal activity. Whether an age-related enhancement of neuronal responses in the visual cortex is coupled with plasticity of AISs is unknown. Here, we compare the AIS length and the distribution of Nav1.6, a key Na+ ion channel in action potential (AP) initiation, along the AIS of layer II/III neurons in the primary visual cortex (V1) of young adult and aged rats, which were examined previously in a single-unit recording study. In that study, we found that V1 neurons in aged rats showed a significantly higher spontaneous activity and stronger visually evoked responses than did neurons in young rats. Our present study shows that the mean AIS length of layer II/III neurons in the V1 area of aged rats was significantly shorter than that of young adult rats. Further, the proportion of AIS with the Nav1.6 distribution was also reduced significantly in aged rats relative to young rats, as indicated by a decrease in the mean Nav1.6 immunofluorescence optical density within AISs and a specific decrease in Nav1.6 immunofluorescence optical density near the proximal region of the AIS. Our results indicate that aging results in both shortening of AISs and reduction of Nav1.6 Na+ ion channel distribution along AISs, which accompanies enhanced neuronal activity. This age-related morphological plasticity may lower the AP amplitude by reducing Na+ ion entry during AP initiation, spare ATPs consumed by Na+ ion pumps during membrane potential restoration, and thus balance the energy expenditure caused by an increased firing rate of cortical neurons during the aging process.