【作者】 李相尧；

【导师】 孙心德；

【作者基本信息】 华东师范大学 ， 生理学， 2007， 博士

【摘要】 调频是人类语音和动物通讯声的重要因素,携带着听觉信息识别相关的时间-频谱信息,对于声信息的识别有重要意义。对调频信息的处理是中枢听觉神经系统的重要特性之一,对其神经机制的研究将有助于人类对听觉信息处理神经机制的深入认识。大鼠的发声中包含丰富的调频信息,行为学研究显示,大鼠可以识别调频声的调频方向和调频速率,大鼠右侧大脑半球更适合于处理调频速率相关的信息,这提示,大鼠的听觉神经系统存在着处理调频信息的相应的神经机制。目前以大鼠为实验动物进行的有关调频信息处理的研究主要在下丘和皮层进行,但对大鼠下丘的研究远不如皮层。一直以来,在大鼠下丘进行的有关调频音的实验都在神经元听反应阈上30 dB进行,而且仅描述了神经元对调频音反应的性质;最近对其它动物的实验结果显示,声音强度影响神经元对调频音反应的特性,不同声音强度下,神经元对调频方向和调频速率的偏好不同;但在大鼠上目前还没有类似的实验报道,大鼠下丘神经元对调频音敏感的相关神经机制的研究也少有报道。本论文在大鼠的下丘详细考察了不同声强度下神经元对调频音反应的特性,以探讨声强度对神经元调频音反应特性的影响;考察神经元对纯音时程的反应特性与神经元对不同带宽调频音反应特性的关系,以探讨产生神经元速率调谐的抑制性旁带、时程调谐机制;通过电刺激方法,激活声源同侧神经元,考察激活声源同侧神经元对对侧神经元听反应的效应,以探讨两侧下丘神经元在调频信息处理中的调制;本论文还以改良的水迷宫实验模式,考察单独听觉线索和具有空间差别的听/视组合线索引导大鼠对空间目标的朝向行为,以探讨听觉线索在大鼠空间定位中的作用,在行为水平上研究大鼠对听觉信息的处理。在28只大鼠上考察了声强度对神经元调频反应特性的影响。共记录88个对纯音和调频音反应的神经元,其中多数(78/88,94%)神经元对调频音的调频方向、调频速率或者同时对两者有偏好:随着声音强度的增加,对调频有偏好的神经元所占的比例降低。统计了38个神经元在MTFM到MTFM+30 dB声强度范围内对调频音的反应,发现有60.5%的神经元对MTFM+30 dB声强度的调频方向偏好在其他声强度下会发生改变;有84.2%的神经元在MTFM+30 dB声音强度下对调频速率偏好和其他声压水平下的反应特性不同。实验结果提示,声音强度可强烈影响神经元对调频信息的处理。统计了对调频音偏好的神经元在相对阈值声强度和实际声强度(相对于20 uPa)不同声强范围所占的比例,结果发现,在闽值强度对调频声偏好的神经元所占的比例明显高于阈上30 dB的比例;而在10-70 dBSPL范围内,对调频音偏好的神经元在各个声强度范围内呈均匀分布。这提示,在大鼠的下丘,单个神经元在相对于其阈值较低的声音强度下对调频信息敏感,同时,不同的神经元的阈值不同,从而保证了在较宽的声强范围内,都有对调频信息敏感的神经元,这可能是下丘调频信息和声强信息相匹配的一种方式。本实验在20只大鼠上考察了神经元对纯音时程反应特性与调频音反应特性的关系,实验使用的声音刺激包括纯音,窄带、宽带调频音,其中窄带调频音的频率范围位于神经元的兴奋性感受野之内,宽带调频音的频率范围位于神经元的兴奋性感受野之外。共记录了80个神经元的声反应,其中完整记录了54个神经元对纯音,窄带、宽带调频音的反应。在26个不表现出纯音时程选择的神经元中,有3个神经元,在调频音刺激时,不表现出对调频速率的偏好;有5个神经元,在窄带调频音刺激时无调频速率选择性,在宽带调频音刺激时有调频速率选择性,提示在大鼠下丘可能存在神经元对调频速率偏好抑制性旁带机制,抑制性旁带不对称分布于神经元兴奋性感受野的周围,如果它参与了神经元调频速率偏好的形成,那么,改变调频音的带宽,使其位于兴奋性感受野内,则神经元对调频速率的偏好将消失。在28个对纯音时程选择的神经元中,16个神经元在三种声音刺激下,对声音时程的反应类型一致,其中12个神经元对调频速率的偏好不受调频音带宽影响。它们对纯音反应的时程0.5,0.8切点可以较好的预测其调频速率反应的0.5,0.8切点,提示这一类神经元对调频速率的偏好可能是由时程调谐的机制产生的。在20只大鼠上,观察了两侧下丘神经元在调频信息处理中的调制,考察了在电刺激声源同侧下丘时,声音对侧下丘神经元的放电率-强度反应曲线,对调频音反应特性的改变情况。结果发现,多数神经元的放电数发生改变,其中多数为放电脉冲数减少,少量增加,这与已有的报道相一致。神经元放电率-强度反应曲线的30-70%动态范围,27.8%(5/18)不改变,27.8%(5/18)增加,33.3%(6/18)缩小,11.1%(2/18)大小不发生改变,但位置移动。92.8%(26/28)神经元对调频速率的偏好发生改变,46.4%的神经元对调频方向的偏好发生改变。实验结果提示,一侧下丘可以调控另一侧下丘神经元对听觉信息的处理。分别使用单独听觉线索和声/光组合线索研究大鼠的空间朝向行为。实验结果发现,单独听觉线索引导时动物的表现优于无线索引导时的表现,说明单独的听觉线索可以引导大鼠进行空间定位。给予具有不同空间差别的声/光组合线索,发现空间方位一致声-光组合信号引导时,动物的反应时间较单独光信号引导显著缩短,正确率提高,表现出明显的听-视整合效应。这种整合效应在光信号强度较弱时更为明显。实验结果提示,大鼠也具有较强的听/视整合能力,且大鼠对听/视信息的整合遵循空间和强度反比规则。更多还原

【Abstract】 Frequency modulation, the basic elements of the human speech and vocalizations of many species, convey the temporal-spectral cues for the recognizing of auditory information. The processing of the frequency modulated information is one most important characteristic of the central auditory nervous system, and the studies of the mechanisms of which will further the investigation the neural mechanisms for the auditory information processing.There are frequency modulated information in the vocalizations of rats, behavioral results had shown that rats can discriminate the modulation rate and direction of the frequency modulation sweeps and the right auditory cortex of rat’s brain was dominance in the discrimination of the direction of frequency modulation sweeps. These data suggested that the frequency modulation information processing mechanisms exist in the central auditory system. Some experiments about the frequency modulation information processing have been conducted on rats’ inferior colliculus (IC) and auditory cortex (AC), while the progress on IC was not fast as that in AC. The experiments about the FM information processing on rat’s IC had always been done on the relative sound intensity, such as 30 dB above the neurons mini-thresholds (MT), while more recently, data from other species suggested that sound intensity will affect the preference of neurons to the FM sweeps, whether the preferred characteristics to the FM sweeps of neurons in rat’s IC are affected by the sound intensity or not is still a question, and the neural mechanisms for the processing of FM information on neurons in rat’s IC has been ignored for a long time. Based on this situation, we designed some experiments to investigate the neural mechanisms for the FM information processing of neurons in rat’s IC. For example, the response characteristics of rat inferior colliculus (IC) neurons to frequency modulated (FM) sounds were studied in a wide range of sound levels to investigate the effects of sound intensity on the preference to FM sweeps, the relationships between preference to duration of pure tone and the preference to modulation rate of FM sweep were studied to investigate the possible sideband inhibition mechanism and duration tuning mechanism for the modulation rate sensitivity. Electric stimulation method was used to change the exciting balance between the neurons of both side of IC to investigate the modulation between them. Modified morris water maze was used to study the orientation behavior induced by the auditory cue alone or audio-visual bimodal cue with spatial disparities to investigate the role of auditory cues to the space navigation.Total 88 neurons, which responded to both pure tone and FM sweeps, were isolated in 28 IC of rats, Nearly 90% of IC neurons exhibited preference to sweep direction and frequency modulation rate (FMR) of FM sweep; the proportions of FM sweep directional selective and FMR preferred neurons varied with sound level. The directional selectivity of nearly 60% of neurons and the FMR preference of 84.2% of neurons determined at 30dB above minimal threshold to FM sound were not consistent with that determined at lower sound levels. The results demonstrate that the intensity of FM sweeps affects the FM response characteristics of most IC neurons. The proportions of neurons exhibited FM preference at sound intensity relative to minimal threshold (MT) to FM were different from that at the intensity relative to the stander basic level-20 uPa, it was significant that the proportion at 0 dB relative to MT was higher than that at 30 dB relative to MT, while this significance disappeared at intensity relative to the stander basic level-20 uPa, this suggested that there maybe one mechanism to code the FM and intensity information at the same time.Twenty rats were used to study the relations between preference to duration of pure tone and the preference to modulation rate of FM sweep, pure tone and narrow band (located in the excited frequency area) FM sweep, broad band (overflow the excited frequency area) were used as sound stimulation to investigate the possible sideband inhibition mechanism and duration tuning mechanism for the modulation rate sensitivity. The side band inhibition was always located beside the excited frequency area, if it is existing and contributed to the modulation rate preference, the preference to modulation rate will be eliminated with the changing of the band range of FM sweep to in the excited frequency area. Total 80 neurons were isolated and the response characteristics to pure tone, narrow band FM sweep and broad band FM sweep of 54 neurons were recorded detailly. Among the 26 neurons, which were not sensitive to the duration of pure tone, 5 neurons keep this no-sensitive characteristic when stimulated with narrow band FM sweeps but show preference to the broad band FM sweep, this suggested that the inhibition side band may contributed to the modulation rate preference to neurons in IC of rats. Total 28 neurons show duration tuning to pure tone, only 16 of them have the same duration response functions under the stimulation of pure tone and FM sweeps, the modulation rate preferences of 12 neurons were not affected by the bandwidth of FM sweeps. The duration 0.5, 0.8 cut-off points of these 12 neurons can predicate the modulation rate 0.5, 0.8 cut-off points perfectly, this suggested that the preference to modulation rate may be created by the mechanism which contributed to the duration tuning of neurons.Total 20 rats were used to study the modulation between the neurons in the bilateral IC. the rate-intensity functions and preference to FM sweeps of neurons in con-sound source IC were recorded before, during and after the electric stimulation of the neurons in the ipsi-sound source IC. Results show that the response of most sampled neurons were changed, and the response pulses of most decreased and little increased, this was similar to the previous report which showed that when the activity of neurons in ipsi-sound source IC decreased the activity of con-IC neurons increased. The 30-70% dynamic ranges of rate-intensity functions of 27.8% (5/18) of neurons were extended and 33.3% were contracted, 11.1% of neurons were not changed but the location of 30% and 70% cut-off point changed. Electric stimulation changed the preference to modulation rate at 92.8% (26/28) of sampled neurons and preference to directions of FM sweeps at 46.4% of sampled neurons. These data suggested that there is modulation between the neurons in bilateral IC of rats.The auditory cue alone and audio-visual cue were used to induce the orientation behavior of rats, respectively. The results showed that rat will orientated better when auditory cue were used alone than random, this suggested that alone auditory beacon can be used to induced the navigation of rats. Under the inducing of the auditory-visual combined cue presented with the spatial and temporal coincidence, the reaction time decreased and the success rate increased than the visual cue induced alone. This suggested that the rat can integrate the information from different modal and have the multi-modal integration ability, and this kind integration will follow the rules generally.更多还原