Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour

Abstract

The present study examined the role of the basal forebrain corticopetal cholinergic projection in the regulation of cortical electroencephalographic activity across sleep/wake states in rats. Selective lesions of this projection were effected by local intraparenchymal infusions of the immunotoxin 192 IgG-saporin. Lesions spared the septo-hippocampal cholinergic system, as well as p75-receptor-bearing noncholinergic neurons in the suprachiasmatic nucleus. Relative to sham-lesioned control animals, rats with lesions of basal forebrain cholinergic neurons displayed a significant reduction in high frequency EEG activity, characterized especially by a reduction in gamma EEG power. Lesions did not significantly alter the overall proportion of sleeping and waking states as defined behaviourally, but the attenuation of high frequency EEG activity was apparent across all stages, including REM-like periods. Results are consistent with the view that the basal forebrain corticopetal cholinergic system exerts a general activational effect on the cortical mantle. Although this system may not be essential for sleep/wake stage-switching, it does impact on the cortical states associated with those stages.

Effects of Ibotenate and 192IgG-Saporin Lesions of the Nucleus Basalis Magnocellularis/Substantia Innominata on Spontaneous Sleep and Wake States and on Recovery Sleep after Sleep Deprivation in Rats

“…The selective loss of cholinergic markers after 192IgG-SAP injections into the SI/NBM, reducing caudal BF cholinergic neurons by 69% and cortical AChE staining by 84%, is consistent with previous reports (Wenk et al, 1980;Heckers et al, 1994;Berntson et al, 2002). Eleven percent of PARV neurons were also lost compared with ACSF controls, probably because of nonspecific uptake of the immunotoxin, or unconjugated SAP contaminant, by neurons damaged during injection.…”

“…Nonselective BF lesions increased delta power in the EEG (Buzsaki et al, 1988;Riekkinen et al, 1990Riekkinen et al, , 1991Vanderwolf et al, 1993), whereas lesions highly selective to cholinergic neurons had relatively minor or no effect on spontaneous EEG or sleep-wake states (Bassant et al, 1995;Kapas et al, 1996;Berntson et al, 2002;Blanco-Centurion et al, 2006).…”

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

“…# P b 0.05, significant change in power before and after drug for a particular group; *P b 0.05, significant difference in power change between lesion and control groups. been previously reported (Wenk et al, 1994;Berntson et al, 2002;Kaur et al, 2008). In addition, Blanco-Centurion et al (2006) reported that NBM lesion by 192IgG-saporin resulted in no change in sleep drive or the daily amounts of sleep-wake activities.…”

“…Sham-lesion rats received bilateral saline infusion (0.5 μl/side) into SI. The volume (0.5 μl) used was identical (Berntson et al, 2002;Kaur et al, 2008), or similar (0.4-0.8 μl used by Heckers et al, 1994;Laalou et al, 2008), to that used in other intra-NBM lesion studies. Saline with or without 192IgG-saporin was delivered by an infusion pump (Harvard Apparatus, South Natick, MA) over 10 min, after which the cannula was kept in place for another 10 min to allow for diffusion before retraction.…”

Gamma band directional interactions between basal forebrain and visual cortex during wake and sleep states

“…Thus, lesions of the BF result in abnormalities of cortical EEG or LFP signals. Increases of delta (1-4 Hz) activity (Buzsaki et al, 1988;Kaur et al, 2008;Fuller et al, 2011) as well as reductions in gamma (30-90 Hz) activity (Berntson et al, 2002) have been reported following BF lesions. Since the cholinergic neurons of the BF are the major source of Acetylcholine to neocortex, much work has focused on the functional role of this projection system.…”