Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice

Abstract

Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma–aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR–PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+–PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+–PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+–PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

Hippocampus Insulin Receptors Regulate Episodic and Spatial Memory Through Excitatory/Inhibitory Balance

“…After deep anesthesia induced by pentobarbital sodium (40 mg/kg), mice of either gender for C57BL/6, InsR fl/fl mice, InsR fl/fl , GAD2 Cre ::InsR fl/fl , Vglut2 Cre ::InsR fl/fl mice and GAD2-Cre::Ai9 mice at an age from 8 to 12 weeks ( n = 3) were perfused as described in detail in our previous report ( Wu et al, 2023 ).…”

“…Elevated Plus Maze Test. As described in our previous report (Wu et al, 2023), the elevated plus maze test (EPM) was made of a white Plexiglas apparatus consisting of two opposing open arms (30 × 5 cm), two opposing closed arms (30 × 5 cm), and a central area (5 × 5 cm). The platform was placed 50 cm above the floor.…”