Spatiotemporal characterization of large-scale brain activity upon generalized arousal transitions

Martínez de Paz, José María (2026): Spatiotemporal characterization of large-scale brain activity upon generalized arousal transitions. Dissertation, LMU München: Faculty of Biology

Abstract

Arousal state has a major impact on perceptual ability, task performance, and diverse aspects of physiology and behavior. During wakefulness, spontaneous fluctuations in arousal state strongly modulate neural activity in numerous brain regions in mice, but the lack of large-scale, deep imaging methods has prevented testing whether these fluctuations affect the entire brain uniformly. Moreover, it remains unclear whether spontaneous and sensory-evoked fluctuations in arousal state engage the same brain circuits or are fundamentally distinct processes. To address this gap, I used functional ultrasound imaging in awake, head-fixed mice to record whole-brain activity upon arousal transitions, measured through the pupil size. I identified a large-scale arousal ‘wave’ of activity from specific brain regions showing a distinct temporal dynamic, from caudal to rostral and from ventral to dorsal areas. This progression was very similar for both spontaneous and evoked arousal transitions, to the point that one condition was predictive of the other. I further performed several control analyses and experiments to ensure that the observed results were due to internal arousal state, and not motor or sensory confounders. Finally, I assessed how the arousal wave is affected by manipulations in the tonic levels of noradrenaline, a well-established regulator of arousal, using optogenetics and pharmacology. I found that the cortical component, but not the subcortical component, of the arousal pattern was sensitive to pharmacological loss of the noradrenergic tone. Bidirectional optogenetic manipulation of the locus coeruleus confirmed different susceptibility to noradrenaline between the cortical and the subcortical components of the wave. Altogether, this work recontextualizes the role of arousal as a global modulator of neural activity by identifying a specific brain network that responds to spontaneous and evoked fluctuations in arousal, and by characterizing its constitutive components across sustained arousal states.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Arousal, Internal states, Behavior, Brain-wide activity, Brain networks, Neuroimaging, fUSi
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 570 Life sciences
• Faculties: Faculty of Biology
• Language: English
• Date of oral examination: 16. April 2026
• 1. Referee: Macé, Emilie
• Signature of the printed copy: 0001/UMC 31931