Reassessment of the structural basis of the ascending arousal system

Abstract

The “ascending reticular activating system” theory proposed that neurons in the upper brainstem reticular formation projected to forebrain targets that promoted wakefulness. More recent formulations have emphasized that most neurons at the pontomesencepahlic junction that participate in these pathways are actually in monoaminergic and cholinergic cell groups. However, cell-specific lesions of these cell groups have never been able to reproduce the deep coma seen after acute paramedian midbrain lesions that transect ascending axons at the caudal midbrain level. To determine whether the cortical afferents from the thalamus or the basal forebrain were more important in maintaining arousal, we first place large cell-body specific lesions in these targets. Surprisingly, extensive thalamic lesions had little effect on EEG or behavioral measures of wakefulness or on c-Fos expression by cortical neurons during wakefulness. In contrast, animals with large basal forebrain lesions were behaviorally unresponsive, had a monotonous sub-1 Hz EEG, and little cortical c-Fos expression during continuous gentle handling. We then retrogradely labeled inputs to the basal forebrain from the upper brainstem, and found a substantial input from glutamatergic neurons in the parabrachial nucleus and adjacent pre-coeruleus area. Cell specific lesions of the parabrachial-precoeruleus complex produced behavioral unresponsiveness, a monotonous sub-1Hz cortical EEG, and loss of cortical c-Fos expression during gentle handling. These experiments indicate that in rats the reticulo-thalamo-cortical pathway may play a very limited role in behavioral or electrocortical arousal, while the projection from the parabrachial nucleus and precoeruleus region, relayed by the basal forebrain to the cerebral cortex, may be critical for this process.

Basal forebrain activation enhances between-trial reliability of low-frequency local field potentials (LFP) and spiking activity in tree shrew primary visual cortex (V1)

“…not significant population activity that may be the reason for the reduced amplitude of the low-frequency-evoked LFP responses in this condition. LFP power modulations have been previously linked to cortical state, such that the desynchronized state is associated with a reduction in low-frequency power in LFP and EEG signals (Bhattacharyya et al 2013;Buzsaki et al 1988;Chen et al 2015;Fuller et al 2011;McLin et al 2002;Metherate et al 1992;Pinto et al 2013). Low-frequency LFP power reduction has been linked to a general suppression in depth-negative waves, which are large-amplitude low-frequency LFP events that occur spontaneously during anesthesia or quiet wakefulness (Harris and Thiele 2011) in the synchronized state.…”

Brain circuitry mediating arousal from obstructive sleep apnea

“…These areas a) have widespread forebrain projections with axons traversing the lesion and stimulation region and b) promote waking or wake-associated phenomena [17]. However systematic studies placing lesions in these cell groups have identified only two subcortical regions that are critically required for maintaining a behaviorally responsive state: the basal forebrain and the parabrachial/precoeruleus region [18]. It is likely that one or more of the structures in the arousal network mediates OSA arousal.…”

Neuromodulation of Vegetative State through Spinal Cord Stimulation: Where Are We Now and Where Are We Going?

“…This model has directed and shaped research on cortical function and sleep-wake regulation, as well as clinical evaluation of patients with loss of consciousness [40]. The projections from the reticular formation to the central thalamus to the cerebral cortex may constitute a critical pathway for maintaining a waking cortical state [41].…”