LAUSR

The regulation of sleep/wake behavior and energy-homeostasis is maintained in part by the lateral-hypothalamic (LH) neuropeptide orexin-A (OXA, hypocretin). Reduction in OXA-signaling is associated with sleep disorders and obesity, whereas higher OXA-signaling promotes obesity resistance. Similarly, dysregulation of hypothalamic neural-networks is associated with onset of age related 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 measure of functional connectivity. Earlier studies show alterations in hypothalamic-synchronicity following behavioral perturbations, in embryonic-neurons obtained from obesity-resistant rats, and following application of OXA onto these cultures. Synchronicity 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 OXA on network-synchronization of these cultures. In addition, we studied wake-promoting effects of OXA in vivo when directly injected into the LH. Our results showed that the adult-hypothalamic-cultures are viable for nearly 3 months in vitro, good quality MEA recordings can be obtained from these cultures, and finally, that cultured adult hypothalamus is responsive to OXA. These results support that adult rat hypothalamic-cultures could be used as a model to study the mechanisms underlying obesity. In addition, LH administration of OXA enhanced wakefulness, indicating that OXA enhances wakefulness partly by promoting neural-synchrony in the hypothalamus.