Role of the midline thalamus in arousal, attention and cognition

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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.