Abstract
Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention on one side, a wakeful state in the middle, and hypervigilance, panic, and psychosis on the other side. However, historically, the concepts of arousal and stress have been challenging to define as measurable experimental variables. Divergent efforts to study these subjects have given rise to several disciplines, including neurobiology, neuroendocrinology, and cognitive neuroscience. We discuss technological advancements that chronologically led to our current understanding of the arousal system, focusing on the multifaceted nucleus locus coeruleus. We share our contemporary perspective and the hypotheses of others in the context of our current technological capabilities and future developments that will be required to move forward in this area of research.
Highlights
The concept of arousal is one that is best defined on a spectrum
In mice null for the DBH gene and rats treated with the Locus Coeruleus (LC)-selective neurotoxin DSP4, we found decreased endogenous Aβ42 levels
The fascinating work of Dr Tsai has elucidated a non-invasive method of induced 40 Hz gamma-band stimulation for the improvement of memory impairment and neuronal loss in Alzheimer’s Disease (AD) by improving the clearance of Aβ42 plaques and hyperphosphorylated tau pathology in several mouse models of AD [260, 261]. While it remains unclear if the LC-NE system is involved in this gamma oscillation related mechanism, there appears to be a promising rationale for further investigation
Summary
The concept of arousal is one that is best defined on a spectrum. Through a clinical lens, behaviors relating to inattention or cognitive dysfunction associated with under-stimulation may reflect mild to moderate levels of an arousal deficiency, with excessive daytime sleepiness and sedation being symptoms of the most extreme cases. The subsequent observation that once a stress or anxiety response was provoked, mental resource allocation could be diverted away from the task at hand and toward task-irrelevant stimuli, resulting in performance deficits [128] This idea is still relevant today as cognitive psychologists continue to discuss theoretical mechanisms for selective attention and the ability of stress to both improve or weaken performance in a state-specific manner. This enabled researchers to hypothesize about the timedependent functional roles of specialized regions within a system that can dictate complex behavioral responses when brought together at a network level This conceptual line of inquiry, combined with continued methodological advancements, shifted our understanding of the neural basis for cognition. In support of this notion, a recent developmental genetic analysis study identified two subpopulations of LC neurons, a majority of which were derived from the alar plate, and a smaller portion, previously undescribed, is negative for a typical marker of alar-plate derived LC neurons [223]
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