Ding Yanxia, Chen Ting, Wang Qin, Yuan Yingying, Hua Tianmiao
College of Life Sciences, Anhui Normal University.
Wannan Medical College, Wuhu, China.
Neuroreport. 2018 Dec 12;29(18):1537-1543. doi: 10.1097/WNR.0000000000001145.
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.
最近的研究表明，神经元轴突起始段（AIS）的结构会随着神经元活动的变化而具有高度可塑性。视觉皮层中与年龄相关的神经元反应增强是否与AIS的可塑性相关尚不清楚。在这里，我们比较了年轻成年大鼠和老年大鼠初级视觉皮层（V1）中II/III层神经元AIS的长度以及Nav1.6（动作电位（AP）起始中的关键钠离子通道）沿AIS的分布情况，这些大鼠先前已在一项单单位记录研究中进行过检测。在该研究中，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显著更高的自发活动和更强的视觉诱发反应。我们目前的研究表明，老年大鼠V1区II/III层神经元的平均AIS长度明显短于年轻成年大鼠。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，这表现为AIS内平均Nav1.6免疫荧光光密度降低以及AIS近端区域附近Nav1.6免疫荧光光密度的特异性降低。我们的结果表明，衰老导致AIS缩短以及沿AIS的Nav1.6钠离子通道分布减少，这伴随着神经元活动增强。这种与年龄相关的形态可塑性可能通过减少AP起始期间的钠离子内流来降低AP幅度，节省膜电位恢复期间钠离子泵消耗的ATP，从而平衡衰老过程中皮层神经元放电率增加所导致的能量消耗。
