The ventral midline thalamus: Participation in neurological and neuropsychiatric disorders

The ventral midline thalamus comprises the reuniens and rhomboid nuclei (ReRh). These nuclei are bidirectionally connected not only with two key brain structures relevant to cognition – the (medial) prefrontal cortex and the hippocampus – but also with over thirty other brain regions, often reciprocally. Over the past two decades, these nuclei have attracted increasing interest for their roles in various memory functions, including working memory and systems consolidation, as well as in behavioral flexibility, emotions such as fear, and the regulation of plasticity. Unsurprisingly, the Re nucleus, and occasionally its neighbor, the Rh nucleus, have been implicated in several neurological conditions and neuropsychiatric disorders. This review focuses on Alzheimer’s disease and epilepsy before addressing neuropsychiatric alterations such as anxiety, depression, chronic stress, schizophrenia, fetal alcohol syndrome, and fear encoding, generalization and extinction. When available, we first discuss clinical studies in humans, often very briefly, followed by experimental approaches using a wide range of animal models. The involvement of the ReRh nuclei in both memory processing and emotional regulation suggests that their dysregulation may represent a common pathological mechanism underlying the cognitive and affective symptoms shared across these disorders. Therefore, understanding the precise contributions of the ReRh nuclei to these diseases could reveal novel therapeutic targets for intervention.