Lateral Hypothalamic Area Glutamatergic Neurons and Their Pro

AAV-taCasp3 was used for pharmacogenetic ablation tests. AAV-hM3Dq and AAV-hM4Di were used for chemogenetics manipulation. AAV-ChR2 and AAV- NpHR were used for optogenetic manipulation. (All viruses were packaged by BrainVTA)

The viruses used in this article from BrainVTA are in the table below

Neuron Ablation	PT-0206 rAAV-Ef1a-DIO-taCasp3-TEVP
Chemogenetics	PT-0042 AAV-Ef1a-DIO-hM3Dq-mCherry PT-0043 AAV-Ef1a-DIO-hM4Di-mCherry
Optogenetic	PT-0002 rAAV-Ef1a-DIO-hChR2-mCherry PT-0007 rAAV-Ef1a-DIO-NpHR-mCherry
Control	PT-0013 rAAV- Ef1a-DIO-mCherry

Shiyi Zhao, Rui Li, Huiming Li, Sa Wang, Xinxin Zhang, Dan Wang, Juan Guo, Huihui Li, Ao Li, Tingting Tong, Haixing Zhong, Qianzi Yang, Hailong Dong
Pub Date: 2021-04-13, DOI: 10.1007/s12264-021-00674-z, Email: [email protected]
The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoﬂurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

Figure 1. Pharmacogenetic ablation of LHA glutamatergic neurons accelerates the induction and prolongs the emergence of anesthesia.

The study is aimed to explore the anesthesia-related effect of glutamatergic neurons in the LHA. Combining pharmacogenetic ablation techniques and optogenetics with ‘‘designer receptors exclusively activated by designer drugs’’ (DREADDs), the authors explored the function of LHA glutamatergic neurons and their projections to the LHb in isoﬂurane anesthesia. The results suggest a potential effect of LHA glutamatergic neurons in the regulation of both the induction and emergence of anesthesia.

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