【作者】 罗凯；

【导师】 吴飞健； 陈其才；

【作者基本信息】 华中师范大学 ， 动物学， 2007， 硕士

【摘要】 声音的时相特征在声音的识别和分类中起关键作用，其中时程、脉冲重复率等是重要的参数。在各级听觉中枢的研究都表明，听觉相关的高级神经活动以及听觉神经元的反应特性与声刺激负载有重要相关性。声刺激呈现率(presentation rate，PR)即单位时间内的给声次数，是反映单位时间内听觉系统接受声刺激能量和信息量的重要指标之一。老年性听力障碍(presbycusis)是指因听觉系统老化而引起的听力下降，其病理改变主要在耳蜗及蜗后，临床表现为高频听力下降、言语识别率降低、脑干诱发电位的潜伏期延长等特征。而临床上presbycusis的主要表现之一就是患者对快速声信号处理能力不足。本研究在自由声场条件下，以所记录神经元的特征频率(characterizing frequency，CF)作为声刺激的频率，强度为最小阈值(minimal threshold，MT)以上10 dB SPL(MT+10 dB)，时程为10 ms、40 ms和120 ms的纯音短声作为刺激，并改变刺激PR(0.5，1，3.3，5，6.7，10，20 Hz)，记录了戊巴比妥钠(pentobarbital)麻醉昆明小鼠(Mus musculus．Km)的下丘(inferior colliculus，IC)神经元的反应，以初步探明衰老及PR对小鼠IC神经元反应的影响以及IC神经元的反应跟随声刺激呈现的能力受声刺激时程的影响。实验共用28只健康昆明小鼠，雌雄不拘，其中幼年鼠12只(3-4 w，体重10—15g)，成年鼠9只(3-4 m，体重30-35g)，老年鼠7只(＞12 m，体重50 g以上)，记录到IC神经元109个，有完整数据的神经元101个。结果发现：在短声强度为MT以上10 dB SPL、时程为40 ms时，随PR的增高，1)大多数的发放数随PR增大而单调递减，其中在幼年鼠中占82.9％，成年鼠占90.9％，老年鼠占81.8％。2)神经元的潜伏期也随PR增大发生剧烈改变，幼年鼠和成年鼠大部分神经元(分别为62.8％和66.7％)的潜伏期随PR增大而逐渐延长，而老年鼠潜伏期随PR单调递增的神经元只占33.3％，明显要低于幼年鼠和成年鼠，体现了年龄上的差异。此外，本研究发现，3组老鼠IC神经元对时程的偏好不同，幼鼠和成年鼠的神经元倾向于在刺激时程为10 ms时产生最大发放(分别占到68.6％和69.7％)，而老年鼠的神经元明显偏好于长时程刺激(在120 ms达最大发放的神经元比例为63.6％)。对3组小鼠IC神经元的发放模式分类显示，幼鼠、成年鼠、老年鼠的P型发放模式分别为：60％、84.8％、60.6％：PB型发放模式分别为：37.1％、12.1％、15.1％；T型发放模式分别为：2.9％、3％、24.2％。可见，老年鼠神经元的T型发放明显多于幼鼠和成年鼠。本研究的结果显示，相同时程下，随着PR增高潜伏期单调变化的比例(31.2％—69.7％)低于发放数随着PR增高而单调变化的比例(81.8％-90.9％)，反映出PR对潜伏期的影响比对发放数的影响要小。老年鼠在声负载增加时其IC神经元声反应潜伏期的波动性较之幼年鼠和成年鼠明显增大。本研究的初步结果揭示，人类衰老过程中出现的听功能下降很可能与听神经元在大声负载条件下的时间表征稳定性下降有关。另外老年鼠对长时程声音刺激的偏好为解释为什么随着衰老，人需要更长、更慢的声刺激环境提供了细胞水平的实验证据。老年鼠神经元的T型发放明显多于幼鼠和成年鼠，可能是由于衰老导致抑制性神经递质水平的下降从而影响神经元反应的类型。至于究竟何种神经回路以及何种神经递质介入了这一过程的发生，我们正在进一步研究之中。更多还原

【Abstract】 Presentation rate of sound stimulations (PR) is the parameter representing the energy and information received by animals in limited time. Presbycusis, literally elder hearing, is the general term applied to age-related hearing loss. The disorder is characterized by reduced hearing sensitivity and speech understanding in noisy environments, slowed central processing of acoustic information, and impaired localization of sound sources. In our experiment, to investigate the effect of PR and age on the sound response properties of mouse inferior collicular (IC) neurons and the relationship between the neurons’ ability to follow sound presentations and the duration as well as intensity of the sounds, the tones with different durations (10、40 and 120 ms), intensities (10 dB SPL above minimal threshold) at characteristic frequency(CF) of recorded neurons were presented to pentobarbital anesthetized mice (Mus musculus, Km) at different PR (0.5, 1, 3.3, 5, 6.7, 10 and 20 Hz) under free field stimulation conditions.28 healthy mice (male or female, 12 young, 9 adult and 7 old) with natural hearing were used for this study and a total of 109 IC neurons were recorded. The results were as follows: 1) When the intensity of the stimulations was 10 dB SPL above MT and the duration was 40 ms, with the PR increasing, the sound response properties of most recorded neurons were dramatically influenced by changing the PR even within low PR range (< 3.3 Hz). The firing rate of the majority of neurons (young 82.9%, adult 90.9%, and old 81.8%, respectively) monotonically decreased with the PR increasing, 2) In young mouse and adult mouse group, the latency of the majority neurons (62.8%, 22/35 and 66.7%, 22/33, respectively) monotonically prolonged with the PR increasing. On the contrary, in old mouse group, latency of most of the neurons (66.7%, 22/33) varied non-monotonically. 3) When the intensity of the stimulations was 10 dB SPL above MT, in young mouse and adult mouse group, the best duration for firing rate is 10 ms (68.6% and 69.7%, respectively), while for old mouse group, this duration is 120 ms (63.6%). 4) The percentage of phasic pattern in young, adult, and old mouse group is 60%, 84.8% and 60.6%, respectively. For phasic-burst pattern is 37.1%, 12.1% and 15.1%, respectively. And for the tonic pattern is 2.9%, 3% and 24.2%, respectively. Obviously, the tonic pattern in old mouse group is much more than in young and adult mouse group.The results indicated that the sound response properties of IC neurons were closely correlated with the PR of sound stimulation even in relatively low PR range.In the same duration, the number of neurons with monotonically changed latency (31.2%-69.7%) were fewer than the number of neurons with monotonically changed firing rate(81.8%-90.9% ) , suggesting the influence of PR on latency is less than on firing rate. The latency of old mouse group fluctuated much heavier than young and adult mouse group. Our preliminary data suggest that presbycusis in human might be related with stability decrease in spectral representation of central auditory neurons under stimulation condition of larger sound loads. The duration preference of old mouse group provides the proper explanation for the reason why the old people prefer longer and slower sound. We suggest that aging results in the inhibitory neurotransmitter reduction in the IC, and this reduction induced more tonic pattern in old mouse group than in young and adult mouse group. What neuronal circuit is involved in and which inhibitory neurotransmitter is responsive for these changes described above should be further explored.更多还原