Pupillometry measures for tracking brain function in health and disease

The size of our pupils changes continuously in response to variations in ambient light levels to regulate the amount of light that reaches the retina for optimizing vision. However, even when exposed to isoluminant conditions, fluctuations in pupil size can be influenced by attention and cognitive processes. Pupillary dilation has been indeed documented for nonvisual factors such as fear or empathy, arousal and attention. Recently, pupillometry, the science of measuring pupil size and its dynamic variations, has raised attention for its capacity to assess directly and non-invasively the activity of the brain. The first part of this doctoral thesis focuses on a comprehensive exploration of pupillometry, seeking to elucidate its role as a pivotal tool in understanding diverse aspects of cognition, emotion, and health. In particular, it will be described the development of a cutting-edge deep learning tool, called MEYE, to perform real-time pupillometry in humans and mice via standard web browsers. MEYE has the potential to facilitate cost-effective assessments in clinical and pre-clinical settings. The thesis also explores pupillometry's potential as a biomarker, investigating pupillary abnormalities in a mouse model of Cdkl5 deficiency disorder, offering insights into attention and arousal implications. Pupillometry proves valuable for non-collaborative and preverbal subjects, enabling longitudinal evaluations in disease progression and therapeutic efficacy. Additionally, the research delves into pupillometry's application in assessing conditioned fear responses and neural plasticity, providing a comprehensive understanding of its utility in studying neuronal and behavioral responses. In the second part of the thesis, the focus shifts to exploring molecular and epigenetic mechanisms governing the dynamic regulation of fear memories. Previous work revealed a significant upregulation of the miR-29 family of microRNAs during postnatal development, particularly miR-29a-3p, which exhibited the most substantial age-dependent increase. MiR-29a targets are enriched in categories related to extracellular matrix, PNN composition, and transcriptional regulation. Moreover, miR-29a has been significantly associated with cognitive trajectory, with higher miR-29a levels correlating with accelerated cognitive decline in humans. The study investigates the influence of miR-29a on the persistence of fear memories, with a specific emphasis on its modulation of the epigenetic landscape.