Role of the midline thalamus in arousal, attention and cognition

描述（由申请人提供）：位于丘脑中线的核（中线核）接收来自大脑区域的传入信息，这些区域对行为和皮层的电活动施加激活作用。中线核依次向前脑的结构发送投射，这些结构参与情感和认知行为，共同构成边缘系统。海马体和内侧前额叶皮层是丘脑中线的两个重要分布部位。这两种结构在记忆的各个方面都起着重要作用。基于其多样化的传入事件和对边缘前脑结构的选择性输出，丘脑中线核似乎在情感和认知功能中发挥着重要作用，可能是通过调节唤醒/注意对认知行为的影响。在这方面，众所周知，对人类丘脑中线的破坏会产生昏迷；它的部分中断导致了一种被称为“最低意识状态”（MCS）的情况，即患者有意识，但通常对周围环境没有意识和反应。希夫和他的同事们展示了一项显著的发现，即对MCS患者的丘脑中线进行深部脑刺激（DBS），恢复了长期休眠（或缺失）的一系列运动和认知功能。令人惊讶的是，尽管它明显直接参与了许多与边缘相关的功能，但相对而言，对RE/中线丘脑的研究却很少。然而，最近的一些研究表明，大鼠的重聚核损伤严重破坏了学习和记忆。我们认为，在边缘系统的“低级”和“高级”区域之间以及边缘前脑结构之间的交流中，丘脑的RE/中线代表了一个关键节点。我们打算从不同的角度研究丘脑中线，特别是团聚核（RE），目的是确定其对情感和认知功能的贡献。具体来说，通过三组实验，我们打算描述：(1)选择性RE损伤对学习和记忆或海马或mpfc依赖功能的影响；(2) RE可逆性失活对海马位置细胞活动的影响，目的是确定RE对位置细胞稳定性的贡献，从而对空间记忆的贡献；(3) RE刺激对海马CA1区内嗅皮质引发的长时程增强（LTP）和海马引发的mPFC区LTP的增强作用。综上所述，这些研究应该为RE对边缘前脑在觉醒/注意、情绪控制中的调节作用提供重要信息

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.