Parallel Arousal Pathways in the Lateral Hypothalamus
| Autor: | Thomas S. Kilduff, Jaime E. Heiss, Akihiro Yamanaka |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty Lateral hypothalamus Population Mice Transgenic Inhibitory postsynaptic potential Mice Internal medicine Acetamides medicine Animals Wakefulness education Clozapine Neurons Orexins education.field_of_study Chemistry General Neuroscience General Medicine Isoquinolines Orexin receptor Anti-Bacterial Agents Orexin Mice Inbred C57BL Endocrinology medicine.anatomical_structure nervous system Doxycycline Hypothalamic Area Lateral Female Orexin Receptor Antagonists Neuron Almorexant Arousal Sleep Antipsychotic Agents medicine.drug |
| Zdroj: | eneuro. 5:ENEURO.0228-18.2018 |
| ISSN: | 2373-2822 |
| DOI: | 10.1523/eneuro.0228-18.2018 |
| Popis: | Until recently, hypocretin (Hcrt) neurons were the only known wake-promoting neuronal population in the lateral hypothalamus (LH), but subpopulations of inhibitory neurons in this area and glutamatergic neurons in the nearby supramammillary nucleus (SuM) have recently been found that also promote wakefulness. We performed chemogenetic excitation of LH neurons in mice and observed increased wakefulness that lasted more than 4 h without unusual behavior or EEG anomalies. The increased wakefulness was similar in the presence or absence of the dual orexin receptor blocker almorexant (ALM). Analysis of hM3Dq transfection and c-FOS expression in LH inhibitory neurons and in the SuM failed to confirm that the increased wakefulness was due to these wake-promoting populations, although this possibility cannot be completely excluded. To evaluate the relationship to the Hcrt system, we repeated the study inOrexin-tTAmice in the presence or absence of dietary doxycycline (DOX), which enabled us to manipulate the percentage of Hcrt neurons that expressed hM3Dq. In DOX-fed mice, 18% of Hcrt neurons as well as many other LH neurons expressed hM3Dq; these mice showed a profound increase in wake after hM3Dq activation even in the presence of ALM. In mice switched to normal chow, 62% of Hcrt neurons expressed hM3Dq along with other LH cells; chemogenetic activation produced even more sustained arousal which could be reduced to previous levels by ALM treatment. Together, these results indicate an LH neuron population that promotes wakefulness through an Hcrt-independent pathway that can act synergistically with the Hcrt system to prolong arousal. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|