Orexin enhances neuronal synchronization in adult rat hypothalamic culture: a model to study hypothalamic function

Research output: Contribution to journalArticlepeer-review

Abstract

The regulation of sleep/wake behavior and energy homeostasis is maintained in part by the hypothalamic neuropeptide orexin A (OXA, hypocretin). Reduction in orexin signaling is associated with sleep disorders and obesity, whereas higher lateral hypothalamic (LH) orexin signaling and sensitivity promotes obesity resistance. Similarly, dysregulation of hypothalamic neural networks is associated with onset of age-related diseases, including obesity and several neurological diseases. Despite the association of obesity and aging, and that adult populations are the target for the majority of pharmaceutical and obesity studies, conventional models for neuronal networks utilize embryonic neural cultures rather than adult neurons. Synchronous activity describes correlated changes in neuronal activity between neurons and is a feature of normal brain function, and is a measure of functional connectivity and final output from a given neural structure. Earlier studies show alterations in hypothalamic synchronicity following behavioral perturbations in embryonic neurons obtained from obesity-resistant rats and following application of orexin onto embryonic hypothalamic cultures. Synchronous network dynamics in adult hypothalamic neurons remain largely undescribed. To address this, we established an adult rat hypothalamic culture in multi-electrode-array (MEA) dishes and recorded the field potentials. Then we studied the effect of exogenous orexin on network synchronization of these adult hypothalamic cultures. In addition, we studied the wake promoting effects of orexin in vivo when directly injected into the lateral hypothalamus (LH). Our results showed that the adult hypothalamic cultures are viable for nearly 3 mo in vitro, good quality MEA recordings can be obtained from these cultures in vitro, and finally, that cultured adult hypothalamus is responsive to orexin. These results support that adult rat hypothalamic cultures could be used as a model to study the neural mechanisms underlying obesity. In addition, LH administration of OXA enhanced wakefulness in rats, indicating that OXA enhances wakefulness partly by promoting neural synchrony in the hypothalamus. NEW & NOTEWORTHY This study, for the first time, demonstrates that adult hypothalamic cultures are viable in vitro for a prolonged duration and are electrophysiologically active. In addition, the study shows that orexin enhances neural synchronization in adult hypothalamic cultures.

Original languageEnglish (US)
Pages (from-to)1221-1229
Number of pages9
JournalJournal of neurophysiology
Volume127
Issue number5
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
The authors thank Martha K. Grace, Dale V. Boeff, and Curtis D. Evans of Minneapolis VAHCS for technical help during the experiments, data collection, and analysis. This work was supported by the Department of Veterans Affairs Grants 5I01BX003004-01A2 and 1I01BX003687-02 (to C. M. Kotz); 5IO1CX001045-03 (to A. P. Georgopoulos), the National Institute of Health Grant 5R01DK100281-03 (to C. M. Kotz), Award Number T32DK083250 from the National Institute of Diabetes and Digestive and Kidney Diseases (to C. M. Kotz), the University of Minnesota McKnight Presidential Chair of Cognitive Neuroscience, the American Legion Brain Sciences Chair (to A. P. Georgopoulos), and the U.S. Department of Defense Award Number W81XWH-15-1-0520 (to A. P. Georgopoulos).

Funding Information:
This work was supported by the Department of Veterans Affairs Grants 5I01BX003004-01A2 and 1I01BX003687-02 (to C. M. Kotz); 5IO1CX001045-03 (to A. P. Georgopoulos), the National Institute of Health Grant 5R01DK100281-03 (to C. M. Kotz), Award Number T32DK083250 from the National Institute of Diabetes and Digestive and Kidney Diseases (to C. M. Kotz), the University of Minnesota McKnight Presidential Chair of Cognitive Neuroscience, the American Legion Brain Sciences Chair (to A. P. Georgopoulos), and the U.S. Department of Defense Award Number W81XWH-15-1-0520 (to A. P. Georgopoulos).

Publisher Copyright:
© 2022 American Physiological Society. All rights reserved.

Keywords

  • adult neuron
  • hypothalamus
  • orexin
  • sleep
  • synchronization

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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