| First Author | Heiss JE | Year | 2024 |
| Journal | Proc Natl Acad Sci U S A | Volume | 121 |
| Issue | 16 | Pages | e2316150121 |
| PubMed ID | 38593074 | Mgi Jnum | J:355023 |
| Mgi Id | MGI:7737628 | Doi | 10.1073/pnas.2316150121 |
| Citation | Heiss JE, et al. (2024) Distinct lateral hypothalamic CaMKIIalpha neuronal populations regulate wakefulness and locomotor activity. Proc Natl Acad Sci U S A 121(16):e2316150121 |
| abstractText | For nearly a century, evidence has accumulated indicating that the lateral hypothalamus (LH) contains neurons essential to sustain wakefulness. While lesion or inactivation of LH neurons produces a profound increase in sleep, stimulation of inhibitory LH neurons promotes wakefulness. To date, the primary wake-promoting cells that have been identified in the LH are the hypocretin/orexin (Hcrt) neurons, yet these neurons have little impact on total sleep or wake duration across the 24-h period. Recently, we and others have identified other LH populations that increase wakefulness. In the present study, we conducted microendoscopic calcium imaging in the LH concomitant with EEG and locomotor activity (LMA) recordings and found that a subset of LH neurons that express Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) are preferentially active during wakefulness. Chemogenetic activation of these neurons induced sustained wakefulness and greatly increased LMA even in the absence of Hcrt signaling. Few LH CaMKIIalpha-expressing neurons are hypocretinergic or histaminergic while a small but significant proportion are GABAergic. Ablation of LH inhibitory neurons followed by activation of the remaining LH CaMKIIalpha neurons induced similar levels of wakefulness but blunted the LMA increase. Ablated animals showed no significant changes in sleep architecture but both spontaneous LMA and high theta (8 to 10 Hz) power during wakefulness were reduced. Together, these findings indicate the existence of two subpopulations of LH CaMKIIalpha neurons: an inhibitory population that promotes locomotion without affecting sleep architecture and an excitatory population that promotes prolonged wakefulness even in the absence of Hcrt signaling. |
