Kalinchuk AV, Kim S, Mccarley RW, Basheer R (2012) Cholinergic basal forebrain neurons contribute to the biochemical and electrophysiological changes in the cortex during sleep deprivation. Neuroscience 2012 Abstracts 486.24. Society for Neuroscience, New Orleans, LA.
Summary: Short term sleep deprivation (SD) (2-3h) increases the levels of inducible nitric oxide (NO) synthase (iNOS)-mediated NO and adenosine (AD) in the basal forebrain (BF) (Basheer et al., 1999; Kalinchuk et al., 2006). We showed recently that the prolongation of SD for 5h triggers similar biochemical changes in the prefrontal/frontal cortex (PFC/FC), the area which receives projections from the BF (Kalinchuk et al., 2010). Lesion of the BF cholinergic cells using immunotoxin 192-IgG saporin attenuates SD-induced AD increase in the BF and recovery non-rapid eye movement (NREM) sleep response (Kalinchuk et al., 2008). However, it is not known whether the cholinergic cells play a role in SD-induced biochemical changes in the cortex. In the current study we lesioned BF cholinergic cells, and compared SD-induced biochemical changes simultaneously in the PFC and BF in the same animals before and after the lesion. We correlated the changes in the biochemical markers, NO and adenosine, with the changes in electrophysiological markers of homeostatic sleep pressure, encephalogram (EEG) theta power during SD and delta power during recovery NREM sleep after SD. Male rats were implanted with electrodes for EEG/electromyogram (EMG) recording and 2 guide cannulae for microdialysis probes targeting BF and PFC. Microdialysis samples were collected simultaneously from both areas every 30 min during 8h SD. Dialysates were analyzed for AD using high performance liquid chromatography (HPLC)/fluorescent detection and for NO metabolites nitrate and nitrite (NOx) using Fluorimetric Assay Kit (Cayman). The lesion of the BF cholinergic cells was performed using the local injections of 192-IgG saporin into the BF, and similar experiment was repeated 2 weeks after the injection. Histochemical analysis confirmed the localization of the probes in the BF and PFC and the quality of the lesion procedure. Before saporin injection, SD induced increases in the levels of NOx and AD, which became significant after 1h (NOx) and 2h (AD) of SD in the BF and after 4h (NOx) and 5h (AD) of SD in the FC. EEG recording detected increases in the intensity of theta power during SD and delta power during following recovery NREM sleep. 2 weeks after saporin injection, SD-induced changes in NOx and AD were significantly attenuated both in the BF and the PFC. Also the increases in theta and delta power were significantly attenuated. We conclude that cholinergic neurons of the BF, which provide strong activating input to the PFC, contribute to the generation of homeostatic sleep pressure during SD, including its biochemical and electrophysiological correlates.
Related Products: 192-IgG-SAP (Cat. #IT-01)