Single-cell calcium imaging and machine learning in fear memory models

Research project description

PhD will investigate mechanisms of fear regulation combining behavioural studies and computational analysis in this multidisciplinary project 

Fear conditioning (FC) and extinction (FE) are key in behaviour and neuropsychiatric disorders. We seek new insights into the mechanisms of fear regulation combining behavioural studies and computational analysis in this multidisciplinary project. 

FC and FE in Tac2-cre mice will involve the Tac2 pathway – the Tac2 gene, Neurokinin B and its specific receptor Neurokinin 3 (Nk3R) – which are crucial for amygdala circuits and key in fear learning.  

Utilising Single-cell calcium imaging (SCCI, Miniscopes) in freely moving mice during FC and FE provides real-time insights into amygdala dynamics. This approach not only identifies neural circuits involved but also aims to unravel Tac2 contribution to FC and FE. 

Incorporating computational analysis of SCCI data, we aim to investigate neuronal activity patterns during fear processes. Beyond global fluorescence measures, spatial tuning analysis would enhance our understanding of the intricate relationship between neural activity and behaviour. 

Machine learning becomes crucial for comprehensive data interpretation in this dual-species analysis. Employing unsupervised machine learning algorithm aids in discerning patterns and uncovering associations within the complex datasets, potentially predicting fear-related responses. 

The strength of this multidisciplinary project lies in seamlessly integrating behavioural, SCCI, and potentially human response data. This comprehensive analysis will explore relationships between genetic variations, neural patterns, and behavioural outcomes, hopefully uncovering convergences and divergences in fear mechanisms between humans and rodents. Innovative and advanced computational methods are needed to investigate these complexities and identify translational relationships. 

Professor Andero will be the main director and responsible for the behavioral and calcium imaging analyses. Professor Schultebraucks will direct the Machine learning analyses in collaboration with the candidate and Professor Andero. 

Academic background / Skills

Candidates must hold a degree that allows admission to the official doctoral programme at UAB.  

Additional requirements for a stronger application are: 

We seek a candidate well-versed in molecular and cell biology, with hands-on experience in histological analysis and fundamental molecular biology laboratory techniques. We require a minimum of six months period spent in a neuroscience laboratory, with a preference for experience in stress or fear-related research. Experience with Miniscopes is also desired. 

We also emphasize the importance of computational modeling skills. The candidate should possess solid knowledge in the field, with the ability to read and code in Matlab and R. Basic knowledge of Python is also required. The candidate should not only be adept at using existing code but also capable of coding new solutions to address project-specific challenges. A foundational understanding of basic statistics is essential for the candidate, better if with a specific focus on its application in biological contexts.

It is recommended the candidate has an interview with Professor Andero before applying for this scholarship

Research group/s description

The laboratory applying for this scholarship is the Translational Mechanisms of Fear Memory lab, led by Prof ICREA Raul Andero, which belongs to the SGR “Neurobiologia de l’estrès i vulnerabilitat a la psicopatologia”. Professor Andero’s group is focused on behavioural and neural mechanisms of stress and memory in the brain. Specifically, the laboratory studies how stress changes molecular processes underlying fear memories in the brains of both animal models and humans. Additionally, they aim to further understand sex differences in these fear memory circuits which will help to find more effective treatments for patients suffering anxiety and fear-based disorders such as Posttraumatic stress disorder (PTSD), panic disorder or specific phobias.