Collicular influence on auditory thalamic neurons

描述（由申请人提供）：我们已经表明下丘（IC）中的兴奋性（多巴胺能）和抑制性（GABA能）细胞投射到听觉丘脑（MGB）中的细胞并与之形成突触。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。 感觉丘脑曾经被认为是一个简单的中继中心，其细胞接收向上的感觉信息并被动地将其发送到皮层。在过去的30年中，已经变得明显的是，情况并非如此，并且丘脑细胞可以以两种不同的响应模式起作用，“爆发”和“紧张”，这取决于电压敏感性钙电导的激活或失活。取决于细胞处于哪种模式，它们对上行兴奋性突触信息的尖峰反应会发生剧烈变化，从而改变它们对皮层的输入，以响应感觉刺激（见谢尔曼，'01）。此外，在爆发模式下丘脑细胞群的同步反应被认为是慢波睡眠期间和某些类型的全身性癫痫发作期间所见的EEG振荡的原因（参见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额外的复杂性。这里，1）与其他感觉丘脑核相比，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影响听觉丘脑细胞，这些细胞不一定显示两种不同的反应模式3）这种从IC到MGB中某些细胞的上行感觉输入可能显示突触可塑性。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。 为了更好地理解听觉丘脑处理感觉信息的相似性和/或差异，重要的是确定1）兴奋性和抑制性IC输入如何以及何时被激活并因此影响丘脑神经元2）这些输入是否影响可以以一种或两种模式响应的细胞3）刺激丘输入是否可以产生突触可塑性（LTP）。在某些MGB细胞中的作用以及其中涉及的增强机制。所提出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.