CAREER: Posttranslational signaling pathways that encode for flexible behaviors

The ability to adjust our behaviors to changes in our environment is critical for survival and independence. Behavioral adaptation engages specific cellular and molecular pathways in the brain that in turn instruct neural activity patterns. The goal of this project is to determine how the removal of proteins in a specific region of the brain known as the hippocampus instructs neural activity patterns to allow species to adapt to changes within their environment.

This knowledge will benefit society as it will determine how disruption of these critical pathways may blunt adaptive behaviors, which have been found to be defective in human neurological conditions that include neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. This project also integrates research on behavioral adaptability with education and outreach activities that target underrepresented STEM groups by creation of an intensive Course-Based Undergraduate Research Experience (CURE) summer program for engagement of skillsets such as experimental design, scientific rigor/reproducibility and data analysis, and through community outreach educational opportunities at regional and local science fairs.

Behavioral adaptation requires the engagement of molecular signaling pathways at individual synapses that subsequently shape neural ensembles. However, the signaling pathways that can promote adaptive learning and memory processes in organisms and why a breakdown of these pathways leads to deadly consequences (e.g., an inability to identify the location of a new food source or escape from predators) is still poorly understood.

The goal of this proposal is to elucidate how posttranslational-dependent protein removal drives changes in synaptic plasticity that update neural representations of a changing spatial behavior. This project uses Mus musculus as a model system to examine the role of protein ubiquitination on the disengagement of a learned behavior and the formation of new ensemble patterns in hippocampus.

It also addresses how altering synaptic protein half-lives modulate long-term potentiation thresholds with changing spatial contingencies. This project addresses key limitations of capturing neural ensembles for molecular and synaptic characterization during select phases of behaviors and uses multi-disciplinary techniques that include modern molecular biology approaches, Genetically Encoded Calcium Indicators, imaging of neural ensembles with a microendoscope, electrophysiology, and advanced analytical skillsets.

Findings from our work will advance our understanding on the posttranslational protein removal mechanisms that drive decision making processes and bring us a step closer to resolving how brain representations remodel in response to sensory experiences in changing environments.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.