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

Abstract

The basal forebrain (BF) is known for its role in cortical and behavioral activation, and has been postulated to have a role in compensatory mechanisms after sleep loss. However, specific neuronal phenotypes responsible for these roles are unclear. We investigated the effects of ibotenate (IBO) and 192IgG-saporin (SAP) lesions of the caudal BF on spontaneous sleep-waking and electroencephalogram (EEG), and recovery sleep and EEG after 6 h of sleep deprivation (SD). Relative to artificial CSF (ACSF) controls, IBO injections decreased parvalbumin and cholinergic neurons in the caudal BF by 43 and 21%, respectively, and cortical acetylcholinesterase staining by 41%. SAP injections nonsignificantly decreased parvalbumin neurons by 11%, but significantly decreased cholinergic neurons by 69% and cortical acetylcholinesterase by 84%. IBO lesions had no effect on sleep-wake states but increased baseline delta power in all states [up to 62% increase during non-rapid eye movement (NREM) sleep]. SAP lesions transiently increased NREM sleep by 13%, predominantly during the dark phase, with no effect on EEG. During the first 12 h after SD, animals with IBO and SAP lesions showed lesser rebound NREM sleep (32 and 77% less, respectively) and delta power (78 and 53% less) relative to ACSF controls. These results suggest that noncholinergic BF neurons promote cortical activation by inhibiting delta waves, whereas cholinergic BF neurons play a nonexclusive role in promoting wake. Intriguingly, these results also suggest that both types of BF neurons play important roles, probably through different mechanisms, in increased NREM sleep and EEG delta power after sleep loss.

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

“…This compares well with a 69% loss of cholinergic neurons after infusion of 0.26 μg 192IgG-saporin in the NBM (Kaur et al, 2008). No significant change in the number of PARV-immunopositive neurons in the NBM was found in the present study, confirming the selectivity of 192IgG-saporin on cholinergic neurons (Heckers et al, 1994;Wenk et al, 1994;Kaur et al, 2008).…”

“…# 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.…”

“…However, BF contains cholinergic, glutamatergic and GABAergic corticopetal projection systems, and considerable effort has been made in attempting to link these specific projection systems to modulations of the cortical EEG. Evidence from lesion studies suggests that selective immunotoxic lesions of the cholinergic projection system are insufficient for causing changes in cortical EEG (Kaur et al, 2008;Fuller et al, 2011). However, more extensive lesions that affect also the GABAergic corticopetal systems have been linked to enhanced delta band EEG activity and very extensive lesions induce a coma-like state with almost exclusive delta wave EEG (Fuller et al, 2011).…”