Role of the midline thalamus in arousal, attention and cognition

描述(申请人提供)：位于丘脑中线的核(中线核)接收来自大脑区域的传入信息，这些区域对行为和大脑皮层的电活动施加激活效应。反过来，中线核团向参与情绪和认知行为的前脑结构发送投射，这些结构共同构成边缘系统。丘脑中线团状核(RE)的两个重要分布部位是海马区和内侧前额叶皮质。这两种结构在记忆的各个方面都起着突出的作用。丘脑中线核团基于其不同的传入和对边缘前脑结构的选择性输出，似乎在情感和认知功能中发挥着重要作用，可能是通过调节觉醒/注意对认知行为的影响。在这方面，人们很好地认识到，破坏人类的中线丘脑会导致昏迷；它的部分破坏会导致一种称为最低限度意识状态(MCS)的情况--即患者有意识但通常没有意识，对周围环境没有反应。Schiff和他的同事证明了MCS患者的中线丘脑深部脑刺激(DBS)恢复了一系列长期处于休眠(或缺失)的运动和认知功能，这是一个引人注目的发现。令人惊讶的是，尽管它显然直接参与了许多与边缘相关的功能，但对RE/中线丘脑的研究相对较少。然而，最近的一些研究表明，大鼠统一核的损伤严重扰乱了学习和记忆。我们认为，RE/中线丘脑在边缘系统的“低”区和“高”区以及边缘前脑结构之间的通信中是一个关键节点。我们打算从不同的角度来研究丘脑中线，特别是联合核(RE)，目的是确定它对情感和认知功能的贡献。具体地说，通过三组实验，我们打算表征：(1)选择性RE损伤对学习和记忆的影响--或对海马或mPFC依赖的功能的影响；(2)RE的可逆失活对海马区位置细胞活动的影响，目的是确定RE对位置细胞稳定从而对空间记忆的贡献；(3)RE刺激对海马CA1区内嗅觉皮质诱发的长时程增强(LTP)和海马区MPFC的LTP的增强作用。总而言之，这些研究应该提供关于RE对边缘前脑在控制唤醒/注意、情绪方面的调制作用的关键信息 以及与意识障碍、精神分裂症和癫痫有直接关系的认知。

DESCRIPTION (provided by applicant): Nuclei lying on the midline of the thalamus (midline nuclei) receive afferent information from regions of the brain that exert activating effects on behavior and on the electrical activity of the cortex. The midline nuclei, in turn, send projection to structures of the forebrain that participate in emotional and cognitive behavior which collectively constitute the limbic system. Two prominent distribution sites of the nucleus reuniens (RE) of the midline thalamus are the hippocampus and medial prefrontal cortex. Both structures serve a prominent role in various aspects of memory. Based on its diverse set of afferents and selective output to structures of the limbic forebrain, the midline nuclei of thalamu appear to serve a prominent role in affective and cognitive functions, perhaps by mediating the effects of arousal/attention on cognitive behavior. In this regard, it is well recognized that destruction of the midline thalamus in humans produces coma; and its partial disruption gives rise to a condition termed the minimally conscious state (MCS) -- or one in which patients are conscious but generally unaware and unresponsive to their surroundings. Schiff and colleagues demonstrated the remarkable findings that deep brain stimulation (DBS) of the midline thalamus in MCS patients restored a range of motor and cognitive functions that had long been dormant (or absent). Surprisingly, despite its apparent direct involvement in a host of limbic-related functions, comparatively little research has been done on the RE/midline thalamus. A few recent studies have shown, however, that lesions of nucleus reuniens in rats severely disrupt learning and memory. We suggest that the RE/midline thalamus represent a critical node in communication between 'lower' and 'higher' regions of the limbic system and among structures of the limbic forebrain. We intend to examine the midline thalamus, and particularly nucleus reuniens (RE), from diverse perspectives with the objective of determining its contribution to affective and cognitive functions. Specifically, with three sets of experiments, we intend to characterize: (1) the effects of selective RE lesions on learning and memory - or on hippocampal- or mPFC-dependent functions; (2) the effects of reversible inactivation of RE on place cell activity in the hippocampus with the aim of determining the contribution of RE to place cell stability and hence to spatial memory; and (3) the potentiating effects of RE stimulation on entorhinal cortical-elicited long term potentiation (LTP) at CA1 of the hippocampus and on hippocampal-elicited LTP at the mPFC. In sum, these studies should provide critical information on the modulatory effects of RE on the limbic forebrain in the control of arousal/attention, affect and cognition with direct implications for disorders of consciousness, schizophrenia and epilepsy.