Collicular influence on auditory thalamic neurons

描述(由申请人提供)：我们已经证明，下丘(IC)中的兴奋性(谷氨酸能)和抑制性(GABA能)细胞都投射到听觉丘脑(MGB)的细胞并在其上突触。我们的长期目标是了解这些兴奋性和抑制性IC输入在塑造MGB细胞反应中的作用。 感觉丘脑曾被认为是一个简单的中继中心，其细胞接收上升的感觉信息，并被动地将其发送到皮质。在过去的30年里，情况显然并非如此，丘脑细胞可以以两种不同的反应模式发挥作用，即依赖于电压敏感钙电导的激活或失活的“爆裂”和“紧张性”。根据细胞所处的模式，细胞对上升的兴奋性突触信息的尖峰反应会急剧改变，从而改变细胞对感觉刺激的输入(见Sherman，‘01)。此外，在爆发模式下，丘脑细胞群体的同步反应被认为是慢波睡眠和某些类型的全身性癫痫发作期间出现脑电振荡的原因(见McCormick和Bal，‘97)。最近主要来自我们实验室的证据表明，在听觉丘脑中发现了更高水平的复杂性。这里，1)与其他丘脑感觉核不同，上行突触信息以兴奋和抑制的形式存在。2)这种上行感觉输入可能正在影响不一定表现出两种不同反应模式的听觉性丘脑细胞，3)这种从IC向MGB内某些细胞的上行感觉输入可能表现出突触可塑性。因此，使用其他感觉系统创建的丘脑功能模型可能不适用于听觉丘脑。 为了更好地理解丘脑听觉处理感觉信息的相似性和/或差异性，重要的是要确定1)兴奋性和抑制性IC输入是如何以及何时被激活从而影响丘脑神经元，2)这些输入是否正在影响能够以一种或两种模式做出反应的细胞，以及3)刺激丘脑输入是否可以在某些MGB细胞中产生突触可塑性(LTP)，以及涉及什么增强机制。拟议的实验将有助于回答这些问题。

DESCRIPTION (provided by applicant): We have shown that both excitatory (glutamatergic) and inhibitory (GABAergic) cells in the inferior colliculus (IC) project to and synapse on cells in the auditory thalamus (MGB). Our long-term objective is to understand the role of these excitatory and inhibitory IC inputs in shaping the responses of cells in the MGB. The sensory thalamus was once considered to be a simple relay center whose cells received ascending sensory information and passively sent it on to the cortex. Over the past 3 decades it has become apparent that this is not the case and that thalamic cells can function in two different response modes, "burst" and "tonic" which depend on the activation or inactivation of a voltage sensitive calcium conductance. Depending upon which mode the cell is in drastically alters their spike response to ascending excitatory synaptic messages and thus changes their input to the cortex in response to sensory stimuli (see Sherman, '01). In addition, the synchronized response of populations of thalamic cells while in the burst mode are believed to be responsible for the EEG oscillations seen during slow wave sleep and during some types of generalized epileptic seizures (see McCormick and Bal, '97). Recent evidence primarily from our lab has indicated that an added level of complexity is found in the auditory thalamus. Here 1) in contrast to other sensory thalamic nuclei, the ascending synaptic information is in the form of both excitation and inhibition 2) this ascending sensory input may be influencing auditory thalamic cells that do not necessarily display the two different response modes and 3) this ascending sensory input from the IC to some cells in the MGB may show synaptic plasticity. Thus, models of thalamic function that have been created using other sensory systems may not be applicable to the auditory thalamus. In order to better understand the similarities and/or differences in auditory thalamic processing of sensory information it is important to determine 1) how and when the excitatory and inhibitory IC inputs are active and thus influencing thalamic neurons 2) whether these inputs are influencing cells that can respond either in one mode or two and 3) whether stimulation of the collicular inputs can generate synaptic plasticity (LTP) in certain MGB cells and what mechanism of potentiation is involved. The proposed experiments will help to answer these questions.