Transplantation of glutamatergic neuronal precursor cells in the paraventricular thalamus and claustrum facilitates awakening with recovery of consciousness

Abstract

Background: Stem cells offer a promising therapeutic strategy for patients with disorders of consciousness (DOC) after severe traumatic brain injury (TBI), but the optimal transplantation sites and cells are not clear. Although the paraventricular thalamus (PVT) and claustrum (CLA) are associated with consciousness and are candidate transplantation targets, few studies have been designed to investigate this possibility. Methods: Controlled cortical injury (CCI) was performed to establish a mouse model of DOC. CCI-DOC paradigm was established to investigate the role of excitatory neurons of PVT and CLA in disorders of consciousness. The role of excitatory neuron transplantation in promoting arousal and recovery of consciousness was determined by optogenetics, chemogenetics, electrophysiology, Western blot, RT-PCR, double immunofluorescence labeling, and neurobehavioral experiments.Results: After CCI-DOC, neuronal apoptosis was found to be concentrated in the PVT and CLA. Prolonged awaking latency and cognitive decline were also seen after destruction of the PVT and CLA, suggesting that the PVT and CLA may be key nuclei in DOC. Awaking latency and cognitive performance could be altered by inhibiting or activating excitatory neurons, implying that excitatory neurons may play an important role in DOC. Furthermore, we found that the PVT and CLA function differently, with the PVT mainly involved in arousal maintenance while the CLA plays a role mainly in the generation of conscious content. Finally, we found that by transplanting excitatory neuron precursor cells in the PVT and CLA, respectively, we could facilitate

Disorders of nomenclature

“…entitled “Transplantation of glutamatergic neuronal precursor cells in the paraventricular thalamus and claustrum facilitates awakening with recovery of consciousness” contains concerning misinformation and dubious interpretation of the reported findings. 1 It centers around the claim that an injury‐associated 3‐min delay to the return of the vestibular righting reflex after anesthesia constitutes a preclinical model of traumatic Disorders of Consciousness (DoC) in mice. This claim is objectively false.…”

Paraventricular thalamus‐insular cortex circuit mediates colorectal visceral pain induced by neonatal colonic inflammation in mice

“…Among the upstream nuclei projecting to the IC, particular attention should be given to the paraventricular thalamus (PVT), as it serves as an important relay station for ascending peripheral signals. 15 PVT is involved in the regulation of animal wakefulness 16,17 and development of colorectal visceral pain induced by substance P in acute pancreatitis. 18 As such, we hypothesized that glutamatergic neurons in the PVT-IC circuit might be involved in the formation of colorectal visceral pain in IBS.…”