Blanco-Centurion CA, Shiromani PJ (2006) Hypocretin-1 stimulates wake and decreases sleep in the basal forebrain of rats with 192-IgG-sap induced lesion of the cholinergic neurons. Neuroscience 2006 Abstracts 458.7. Society for Neuroscience, Atlanta, GA.
Summary: Hypocretin (orexin) containing neurons are located in the lateral hypothalamus (LH) from where they project to major arousal centers in the brain including the basal forebrain (BF). Waking, in part, may be driven by the action of HCRT on BF neurons. However, the BF contains various phenotypes of neurons and to test whether HCRT stimulates wake via the cholinergic neurons we utilize 192-IgG-saporin (192-IgG-SAP) to lesion the BF cholinergic neurons and then determine the potency of HCRT-1 in stimulating wake. Sprague-Dawley rats were administered (under anesthesia) saline (n=5) or 192IgG-SAP (4-6 ug/6ul, n=7). Three weeks later microinjections of aCSF or HCRT (0.06, 0.125, 0.25 nmol/250ul) were administered to the BF via a cannula in a random order. Sleep was recorded for 6h. In lesioned rats 95% of the BF cholinergic neurons were destroyed. However, in these rats, HCRT-1 in a dose-dependent manner significantly increased the time to onset of NREM and REM sleep and this was not different compared to non-lesioned rats. Percent wake was also not different compared to non-lesioned rats. Four hours after microinjection, wake-sleep levels were back to normal. Two studies (Espana et al., 2001) (Thakkar et al., 2001) have infused HCRT-1 into the BF and monitored changes in sleep-wake. However, because the BF contains a heterogenous population of neurons, HCRT-1 is likely to act on all of the BF neurons that contain the HCRT receptor. Here, we found that in the absence of the BF cholinergic neurons HCRT-1 increased wake and decreased sleep to the same degree as in non-lesioned rats, suggesting that non-cholinergic BF neurons are able to mediate unabated HCRT’s arousal signal.
Related Products: 192-IgG-SAP (Cat. #IT-01)