Modulation of Forebrain Electroencephalographic Activity in Halothane-Anesthetized Rat via Actions of Noradrenergic β-Receptors within the Medial Septal Region

Abstract

The locus coeruleus (LC)-noradrenergic system modulates forebrain electroencephalographic (EEG) activity in halothane-anesthetized rat. For example, unilateral enhancement of LC neuronal activity increases cortical EEG (ECoG) and hippocampal EEG (HEEG) indices of arousal bilaterally (Berridge and Foote, 1991). Conversely, bilateral suppression of LC discharge activity increases EEG measures of sedation (Berridge, et al., 1993b). The EEG-activating effects of LC stimulation appear to involve noradrenergic beta-receptors (Berridge and Foote, 1991). Two candidate sites at which LC efferents could influence ECoG and HEEG are the medial septum/vertical limb of the diagonal band of Broca (MS) and the substantia innominata/nucleus basalis of Meynert (SI). To determine whether norepinephrine mediates such actions within either of these regions, the EEG effects of small infusions of a beta-agonist or antagonist into MS or SI were examined in halothane-anesthetized rat. Unilateral infusions (150 nl) of the beta-agonist isoproterenol (ISO) (3.75 microg, 17 nmol) into MS, but not SI (150-450 nl), elicited robust bilateral activation of ECoG and HEEG. Infusions of glutamate (0.5 microg, 3.0 nmol) into either MS or SI elicited bilateral ECoG and HEEG activation. Neither vehicle infusions into MS nor infusions of ISO into regions adjacent to MS altered forebrain EEG activity. Bilateral, but not unilateral, MS infusions of the beta-antagonist timolol (3.75 microg, 8.7 nmol) decreased EEG indices of arousal in the lightly anesthetized preparation. Power spectral analyses provided quantitative confirmation of these qualitative observations. These results indicate that under these experimental conditions, noradrenergic efferents, presumably arising from LC, modulate forebrain EEG state via actions at beta-receptors located within MS. The results presented in the accompanying report extend these observations to the unanesthetized preparation and incorporate additional measures of behavioral state.

Different Subtypes of Striatal Neurons Are Selectively Modulated by Cortical Oscillations

“…In practical terms, halothane enabled a high level of stability that allowed us to record relatively stationary neuronal activity over long periods of time, aiding both spike sorting and data analysis. As with other anesthetics, the exact mechanism of action of halothane is unknown; however, the major frequencies observed are consistent with those previously described in the cortex of halothaneanesthetized rats (Berridge and Foote, 1991;Berridge et al, 1996;Imas et al, 2004). Halothane is also known to block gap junctions (Johnston et al, 1980), which simplifies the interpretation of the cross-correlation results (see below).…”

Organization of hypocretin/orexin efferents to locus coeruleus and basal forebrain arousal‐related structures

“…In the case of MS, MPOA, and SI, previous mapping studies indicate wake-promoting actions of HCRT and other neurotransmitters within these general regions of the basal forebrain (Kumar et al, 1986;Mallick and Alam, 1992;Berridge and Foote, 1996;Berridge et al, 1996Berridge et al, , 1999Berridge et al, , 2003Berridge and O'Neill, 2001;Thakkar et al, 2001;Españ a et al, 2001). As defined in previous studies, these regions are relatively large and anatomically complex.…”

Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation

“…The medial septum is a major hippocampal afferent and both structures are heavily innervated by NE fibers (Loy et al 1980). Activation of LC-NE neurons or increased NE neurotransmission within septum induces theta rhythmicity of the medial septal neurons and augments theta-oscillatory activity in hippocampus (Berridge and Foote 1991;Berridge et al 1996;Hajos et al 2003;Kitchigina et al 2003;Brown et al 2005). Thus, there appear antagonistic relationships between the septohippocampal and the ripple-generation networks.…”