Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.
摘要
老年性聋,即与年龄相关的听力损失,在我们这个老龄化社会中是一个日益严重的问题。它涉及听觉系统外周和中枢部分的变化。在衰老的Fischer 344(F344)大鼠中,已显示下丘(IC)存在与年龄相关的变化,包括γ-氨基丁酸(GABA)水平降低、谷氨酸脱羧酶水平降低、GABAB受体结合减少,以及轴突终末重排。在C57和CBA小鼠的下丘中也注意到了与年龄相关的生理变化。2. 鉴于抑制性神经递质系统存在与年龄相关的改变,我们推测衰老的F344大鼠的下丘神经元生理反应特性会因影响神经元放电的抑制和兴奋相对水平失衡而发生改变。3. 对297只氯胺酮/赛拉嗪麻醉的老年(24个月)F344大鼠的下丘神经元进行了体内细胞外单单位记录。根据电极轨迹标记和辣根过氧化物酶标记确定记录单位的位置。将结果与年轻成年(3个月)动物的结果进行比较。4. 平均阈值从年轻大鼠的25.4 dB SPL增加到老年大鼠的56.1 dB SPL。5. 尽管老年动物中记录到的处于频率范围两端的单位百分比有所降低,但两组之间的特征频率(CF)范围和平均值没有差异。6. 就整个下丘而言,在自发活动、首次放电潜伏期、动态范围、具有非单调对侧CF音调速率/强度函数(RIFs)的单位百分比或对CF音调呈现速率变化敏感的单位百分比方面未发现差异。7. 在老年大鼠中,较高百分比的单位对听觉刺激反应不佳。8. 在老年大鼠中,最大放电率降低了12%,在其时间反应模式中归类为起始型的单位百分比增加了12%,在高于阈值30 dB时等强度函数的宽度增加了18%。9. 下丘中央核(CIC)与年龄相关的变化通常不同于在下丘外部皮质(ECIC)中观察到的变化。在CIC中,归类为具有非单调对侧音调RIFs的单位百分比随年龄下降,但在ECIC中随年龄增加,并且在CIC中归类为在其时间反应模式中起始型的单位百分比随年龄增加,但在ECIC中不随年龄变化。10. 本研究结果支持这样的假设,即大多数CIC单位的工作范围内存在与年龄相关的向更高强度的转变,同时在抑制性处理方面存在小的、选择性的缺陷。当与其他研究人员进行的小鼠衰老研究以及对年轻和老年恒河猴视觉系统(外侧膝状体核)单个单位的类似研究结果相结合时,这些结果表明随着动物衰老,补偿机制在感觉系统中高度活跃。尽管存在导致下丘输入减少的缺陷以及影响神经递质水平的神经化学变化,但老年大鼠的下丘神经元能够以与年轻大鼠中观察到的非常相似的方式对大多数简单听觉刺激做出反应。