Stressing the other paraventricular nucleus

Fraser, Kurt M.; Janak, Patricia H.

doi:10.1038/s41593-018-0178-1

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Prior work has shown that pharmacological activation of the PVT in vivo induces dopaminergic neuron activity in the VTA, and that converging inputs of the hippocampus and PVT on the NAc regulate dopamine in the VTA (Li and Kirouac, 2008). However, recent work suggests dopaminergic fibers in the PVT originate from the hypothalamus and PAG or stress-induced dopamine modulation from the LC (Li et al, 2014;Beas et al, 2018;Fraser and Janak, 2018), and not from traditional dopaminergic centers such as the VTA. Although the current work does not measure reward-related activation of this circuit, the results demonstrate stationary correlations between these regions and the PVT at rest, consistent with the underlying circuitry.…”

Section: Brainstem and Midbrainmentioning

confidence: 99%

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Kark

Birnie

Baram

et al. 2021

Front. Integr. Neurosci.

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The paraventricular thalamic nucleus (PVT) is a small but highly connected nucleus of the dorsal midline thalamus. The PVT has garnered recent attention as a context-sensitive node within the thalamocortical arousal system that modulates state-dependent motivated behaviors. Once considered related to generalized arousal responses with non-specific impacts on behavior, accumulating evidence bolsters the contemporary view that discrete midline thalamic subnuclei belong to specialized corticolimbic and corticostriatal circuits related to attention, emotions, and cognition. However, the functional connectivity patterns of the human PVT have yet to be mapped. Here, we combined high-quality, high-resolution 7T and 3T resting state MRI data from 121 young adult participants from the Human Connectome Project (HCP) and thalamic subnuclei atlas masks to investigate resting state functional connectivity of the human PVT. The 7T results demonstrated extensive positive functional connectivity with the brainstem, midbrain, ventral and dorsal medial prefrontal cortex (mPFC), anterior and posterior cingulate, ventral striatum, hippocampus, and amygdala. These connections persist upon controlling for functional connectivity of the rest of the thalamus. Whole-brain contrasts provided further evidence that, compared to three nearby midline thalamic subnuclei, functional connectivity of the PVT is strong with the hippocampus, amygdala, ventral and dorsal mPFC, and middle temporal gyrus. These findings suggest that, even during rest, the human PVT is functionally coupled with many regions known to be structurally connected to rodent and non-human primate PVT. Further, cosine similarity analysis results suggested the PVT is integrated into the default mode network (DMN), an intrinsic connectivity network associated with episodic memory and self-referential thought. The current work provides a much-needed foundation for ongoing and future work examining the functional roles of the PVT in humans.

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Section: Brainstem and Midbrainmentioning

confidence: 99%

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Kark

Birnie

Baram

et al. 2021

Front. Integr. Neurosci.

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show abstract

“…These neurons release orexin neuropeptides, OXA and OXB, which bind to and activate two Gαq-protein-coupled receptors, OX 1 R and OX 2 R 16 , which, once activated, increase intracellular calcium concentrations 54,55 . Although orexins were originally discovered for their role in regulating sleep and wakefulness 14,22 , they have now been implicated in host of other behaviors, including avoidance behavior 56 , drug-seeking behavior 23,24 , and psychosis 25 . Of interest to the current project, is the ability of both OXA and OXB to dosedependently modulate PVT neuron activity and the ability of a DORA to reverse aberrant dopamine neuron activity when administered directly in the PVT 26,27 .…”

Section: Discussionmentioning

confidence: 99%

Orexin receptor antagonists reverse aberrant dopamine neuron activity and related behaviors in a rodent model of stress-induced psychosis

et al. 2021

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Post-traumatic stress disorder (PTSD) is a prevalent condition affecting approximately 8% of the United States population and 20% of United States combat veterans. In addition to core symptoms of the disorder, up to 64% of individuals diagnosed with PTSD experience comorbid psychosis. Previous research has demonstrated a positive correlation between symptoms of psychosis and increases in dopamine transmission. We have recently demonstrated projections from the paraventricular nucleus of the thalamus (PVT) to the nucleus accumbens (NAc) can regulate dopamine neuron activity in the ventral tegmental area (VTA). Specifically, inactivation of the PVT leads to a reversal of aberrant dopamine system function and psychosis-like behavior. The PVT receives dense innervation from orexin containing neurons, therefore, targeting orexin receptors may be a novel approach to restore dopamine neuron activity and alleviate PTSD-associated psychosis. In this study, we induced stress-related pathophysiology in male Sprague Dawley rats using an inescapable foot-shock procedure. We observed a significant increase in VTA dopamine neuron population activity, deficits in sensorimotor gating, and hyperresponsivity to psychomotor stimulants. Administration of selective orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) antagonists (SB334867 and EMPA, respectively) or the FDA-approved, dual-orexin receptor antagonist, Suvorexant, were found to reverse stress-induced increases in dopamine neuron population activity. However, only Suvorexant and SB334867 were able to reverse deficits in behavioral corelates of psychosis. These results suggest that the orexin system may be a novel pharmacological target for the treatment of comorbid psychosis related to PTSD.

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Stressing the other paraventricular nucleus

Cited by 2 publications

References 13 publications

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

Orexin receptor antagonists reverse aberrant dopamine neuron activity and related behaviors in a rodent model of stress-induced psychosis

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