Paraventricular thalamic nucleus: Subcortical connections and innervation by serotonin, orexin, and corticotropin-releasing hormone in Macaque monkeys

The present study examines subcortical connections of paraventricular thalamic nucleus (Pa) following small anterograde and retrograde tracer injections in cynomolgus monkeys (Macaca fascicularis). An anterograde tracer injection into the dorsal midline thalamus revealed strong projections to the accumbens nucleus, basal amygdala, lateral septum, and hypothalamus. Retrograde tracer injections into these areas labeled neurons specifically in Pa. Following a retrograde tracer injection into Pa, labeled neurons were found in the hypothalamus, dorsal raphe, and periaqueductal gray. Pa contained a remarkably high density of axons and axonal varicosities immunoreactive for serotonin (5-HT) and orexin/ hypocretin (ORX), as well as a moderate density of fibers immunoreactive for corticotropin-releasing hormone (CRH). A retrograde tracer injection into Pa combined with immunohistochemistry demonstrated that ORX and 5-HT axons originate from neurons in the hypothalamus and midbrain. Pa-projecting neurons were localized in the same nuclei of the hypothalamus, amygdala, and midbrain as CRH neurons, although no double labeling was found. The connections of Pa and its innervation by 5-HT, ORX, and CRH suggest that it may relay stress signals between the midbrain and hypothalamus with the accumbens nucleus, basal amygdala, and subgenual cortex as part of a circuit that manages stress and possibly stress-related psychopathologies.