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Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation

Gelegen, Cigdem ; Miracca, Giulia ; Ran, Mingzi Z. ; Harding, Edward C. ; Ye, Zhiwen ; Yu, Xiao ; Tossell, Kyoko ; Houston, Catriona M. ; Yustos, Raquel ; Hawkins, Edwin D. ; Vyssotski, Alexei L. ; Dong, Hailong L. ; Wisden, William ; Franks, Nicholas P.

Current biology, 2018-02, Vol.28 (4), p.580-587.e5 [Periódico revisado por pares]

England: Elsevier Inc

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Título:
Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation
Autor: Gelegen, Cigdem ; Miracca, Giulia ; Ran, Mingzi Z. ; Harding, Edward C. ; Ye, Zhiwen ; Yu, Xiao ; Tossell, Kyoko ; Houston, Catriona M. ; Yustos, Raquel ; Hawkins, Edwin D. ; Vyssotski, Alexei L. ; Dong, Hailong L. ; Wisden, William ; Franks, Nicholas P.
Assuntos: anesthetic mechanisms ; Anesthetics, Intravenous - metabolism ; Animals ; Glutamic Acid - metabolism ; Habenula - drug effects ; Habenula - physiology ; HEK293 Cells ; Humans ; Hypnotics and Sedatives - pharmacology ; Male ; Mice ; Neural Pathways - drug effects ; Neural Pathways - physiology ; neuronal circuitry ; orexin ; Propofol - pharmacology ; sedative ; sleep architecture ; tetanus toxin
É parte de: Current biology, 2018-02, Vol.28 (4), p.580-587.e5
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These authors contributed equally
Descrição: The lateral habenula has been widely studied for its contribution in generating reward-related behaviors [1, 2]. We have found that this nucleus plays an unexpected role in the sedative actions of the general anesthetic propofol. The lateral habenula is a glutamatergic, excitatory hub that projects to multiple targets throughout the brain, including GABAergic and aminergic nuclei that control arousal [3–5]. When glutamate release from the lateral habenula in mice was genetically blocked, the ability of propofol to induce sedation was greatly diminished. In addition to this reduced sensitivity to propofol, blocking output from the lateral habenula caused natural non-rapid eye movement (NREM) sleep to become highly fragmented, especially during the rest (“lights on”) period. This fragmentation was largely reversed by the dual orexinergic antagonist almorexant. We conclude that the glutamatergic output from the lateral habenula is permissive for the sedative actions of propofol and is also necessary for the consolidation of natural sleep. •Blocking the output of the LHb greatly diminishes the sedative effects of propofol•Natural NREM sleep is also highly fragmented, particularly during “lights on”•Stimulating the lateral habenula suppresses motor activity Gelegen et al. show that the lateral habenula is a key hub whose excitation is permissive for the sedative effects of propofol. When the output from the lateral habenula is blocked, propofol’s sedative effects are greatly diminished, and NREM sleep is highly fragmented.
Editor: England: Elsevier Inc
Idioma: Inglês

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Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation

Gelegen, Cigdem ; Miracca, Giulia ; Ran, Mingzi Z. ; Harding, Edward C. ; Ye, Zhiwen ; Yu, Xiao ; Tossell, Kyoko ; Houston, Catriona M. ; Yustos, Raquel ; Hawkins, Edwin D. ; Vyssotski, Alexei L. ; Dong, Hailong L. ; Wisden, William ; Franks, Nicholas P.

England: Elsevier Inc

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