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产生激活作用。中线核团反过来将投射发送到参与情绪和认知行为的前脑结构，这些结构共同构成边缘系统。丘脑中线的连合核（RE）的两个主要分布部位是海马和内侧前额叶皮质。这两种结构在记忆的各个方面都发挥着重要作用。基于其多样的传入和选择性输出到边缘前脑的结构，丘脑中线核似乎在情感和认知功能中起着重要作用，可能是通过介导唤醒/注意对认知行为的影响。在这方面，众所周知，人类中线丘脑的破坏会导致昏迷;其部分破坏会引起一种称为最低意识状态（MCS）的状况-或患者有意识但通常对周围环境无意识和无反应的状态。Schiff及其同事证明了一项显着的发现，即MCS患者中线丘脑的深部脑刺激（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，尽管其明显的直接参与了主机的边缘相关的功能，相对较少的研究已经做了RE/中线丘脑。然而，最近的一些研究表明，损伤大鼠的连合核会严重破坏学习和记忆。我们认为，RE/中线丘脑代表边缘系统的“低”和“高”区域之间的通信和边缘前脑的结构之间的一个关键节点。我们打算检查中线丘脑，特别是核reuniens（RE），从不同的角度与目标，以确定其对情感和认知功能的贡献。具体地说，我们打算用三组实验来表征：（1）选择性RE损伤对学习和记忆或对海马或mPFC依赖性功能的影响;（2）RE可逆失活对海马中位置细胞活性的影响，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刺激对内嗅皮层诱发的海马CA 1区长时程增强（LTP）和内嗅皮层诱发的mPFC区长时程增强（LTP）的增强作用。总之，这些研究应提供关键信息的调节作用，RE对边缘前脑的控制觉醒/注意，情感 和认知与意识障碍，精神分裂症和癫痫症的直接影响。

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.