The role of lateral hypothalamic GABAergic and glutamatergic neurons in thermoregulation and thermal nociception

Authors

• H Kim
• A Garcia
• Y Aponte

Abstract

The lateral hypothalamus (LH) receives inputs from the ventral lateral periaqueductal gray (vlPAG), which plays an important role in modulating nociception and thermoregulation. However, little is known about the LH cell types that control these survival behaviors. Here, we investigate the effects of LH excitatory (LH-VGLUT2) and inhibitory (LH-VGAT) neuron types on thermoregulation and thermal nociception using chemogenetic manipulations. Our results revealed that chemogenetic activation of LH-VGAT neurons increases both the sensitivity to painful thermal stimuli and temperature preferences toward colder noxious zones. Interestingly, chemogenetic LH-VGLUT2 activation and inhibition decreased and increased thermal nociception, respectively. Moreover, activation of LH-VGLUT2 shifted thermal preference towards warmer temperature zones suggesting that their activation induces analgesia. To determine whether our behavioral results were related to changes in core body temperature (CBT), telemeters were implanted to monitor CBT and locomotion during chemogenetic manipulations. Surprisingly, activation of LH-VGAT and LH-VGLUT2 neurons increased CBT and locomotor activity relative to baseline and saline injection. Together, our results suggest that the increase in CBT triggered by LH VGAT activation facilitates both thermal pain and preference for cold zones. However, further research is needed to evaluate the mechanism underlying thermoregulation by LH VGLUT2 neurons. In future experiments, we will examine whether both cell types play a role in regulating other types of pain. In addition, we will evaluate the functional role of the vlPAG – LH pathway in modulating nociception and thermoregulation.

Scientific Focus Area: Neuroscience

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