Synaptic Plasticity in the Inferior Colliculus

描述(由申请人提供)：我们的总体目标是了解活动如何改变下丘(IC)的听觉信号处理，IC是大脑中的一个关键听觉中枢。 中脑。作为听觉通路的中脑中枢，中央核团中的神经元整合了不同类型的上行听觉信息。IC还通过直接刺激和直接抑制内侧膝状体，将信息门控到听觉皮质。IC的独特位置使其成为最近脑深部刺激的目标。然而，对于诱发的活动，无论是声学还是电学，我们知之甚少。 改变IC神经元的信息传递。突触输入在形成中枢神经元对声音的反应中起着关键作用。在中枢神经系统中，众所周知，突触可以被修饰，例如，以依赖活动的方式增强或抑制。突触可塑性可能对学习记忆和神经回路的发育起重要作用。虽然长时程增强(LTP)和抑制(LTD)在IC中存在，但它们的作用尚不清楚。他们可能会根据成年人听觉通路的最新活动来塑造神经元对声音的反应。突触可塑性的一个关键因素是棘波活动前后的相对时间。峰时相关可塑性(STDP)是一种评估这种关系的正式方法，当使用不同的时间顺序时，经常在同一神经元中诱导LTP和LTD。我们的项目将阐明集成电路中STDP的特征。自.以来 声音加工和STDP现象在同一毫秒的时间范围内都有时间上的变化，STDP可能与声音的突触加工高度相关。此外，在突触可塑性的实验研究中使用STDP的一个明显优点是，可塑性的位置清楚，并且仅限于记录到的神经元在IC内突触前和/或突触后的位置。我们的主要目标是研究活体活动如何改变小鼠下丘的声诱发反应。为此，我们将录制声音唤起的 用细胞旁/细胞附着或整体细胞活体记录技术的神经反应。我们将使用STDP，通过将声音诱发的反应与单细胞电流注射(纳米刺激)诱发的动作电位相结合，来比较神经元经“训练”前后对声音的反应。单独的实验将研究STDP对声音的频谱(频率)调谐、与通信相关的声音的时间调制以及与声音定位相关的双耳刺激的反应的影响。在补充性实验中，我们将使用IC的脑切片制备来研究不同神经元类型的STDP是否相同。具体地说，我们将在GAD67-GFP转基因小鼠中测试GABA能神经元和谷氨酸能神经元，其中GABA能神经元被标记。一般来说，IC和较低的听觉中枢被认为没有听觉皮质那么“可塑性”。我们的项目可能会改变这一观点，并揭示IC中与生理相关的活动依赖性变化。这些知识对于理解正常的听力以及听力损失后的治疗、训练和康复可能是必不可少的。

DESCRIPTION (provided by applicant): Our overall goal is to understand how activity may alter auditory signal processing in the inferior colliculus (IC), a critical auditory center in the midbrain. As the midbrain hub of the auditory pathway, the neurons in the central nucleus of the IC integrate different types of ascending auditory information. The IC also gates the information reaching the auditory cortex through direct excitation and direct inhibition of the medial geniculate body. The unique position of IC has made it a recent target for deep brain stimulation. However, little is known about how evoked activity, either acoustic or electrical, may alter information transmission in IC neurons. Synaptic inputs are critical in shaping the responses of IC neurons to sound. In the central nervous system, it is well known that the synapses may be modified, e.g. potentiated or depressed in an activity dependent manner. Synaptic plasticity may play an important role for learning & memory and the development of neural circuits. Although long term potentiation (LTP) and depression (LTD) exist in the IC, their role is unclear. They might shape the neuronal responses to sound based on recent activity in the auditory pathway in adults. One critical factor in synaptic plasticity is the relative timing between the pre- and post- spike activity. Spike Timing Dependent Plasticity (STDP) is a formal way of evaluating that relationship often inducing both LTP and LTD in the same neuron when a different temporal order is used. Our project will elucidate the character of STDP in the IC. Since both sound processing and STDP phenomena vary temporally in the same millisecond time range, STDP may be highly relevant for the synaptic processing of sound. Moreover, a distinct advantage of using STDP in the experimental study of synaptic plasticity is that the location of the plasticity is clear and is restricted to the pre- and/or post synaptic sites of the recorded neuron in the IC. Our main goal is to investigate how activity may change the sound evoked responses in the inferior colliculus in mice in vivo. For this purpose, we will record sound-evoked neural responses with either juxtacellular/cell-attached or whole cell in vivo recording techniques. We will use STDP to compare the response to sound before and after the neuron is "trained" by combining the sound evoked response with action potentials evoked by single-cell current injection (nano-stimulation). Separate experiments will investigate the effects of STDP on spectral (frequency) tuning to sound, temporal modulation of sound relevant for communication, and responses to binaural stimuli relevant to sound localization. In complementary experiments, we will use a brains slice preparation of IC to investigate whether STDP is the same in different neuron types. Specifically, we will test GABAergic and glutamatergic neurons in GAD67-GFP transgenic mice where GABAergic neurons are labeled. Generally, the IC and lower auditory centers are considered less 'plastic' than auditory cortex. Our project may change this view and reveal physiologically relevant activity-dependent changes in IC. Such knowledge may be essential to understand normal hearing and for therapy, training, rehabilitation after hearing loss.