Assessing Excitation-Transcription Coupling in SCN2A-Related Disorder Mouse Models
Awardee: Jennifer Kearney
Institution: Northwestern University
Grant Amount: $62,492
Funding Period: February 1, 2025 - January 31, 2026
Summary:
Excitation-transcription coupling is a process that facilitates learning and adaptation to new experiences/stimuli by connecting brain activity to changes in neuronal connections. Altered excitation-transcription coupling has been implicated in other neurodevelopmental disorders and may underlie disrupted sensory processing. SCN2A plays a critical role in backpropagation of action potentials, which is an important electrical signal for excitation-transcription coupling. This raises the possibility that excitation-transcription coupling may be altered in SCN2A-related disorders. Our project will investigate whether excitation-transcription coupling is affected in three SCN2A-related disorder mouse models carrying variants with loss-of-function, gain-of-function or mixed effects on channel function. First, we will examine excitation-transcription capability in isolated neurons. Next, we will evaluate excitation-transcription coupling in mice engaging in behavioral tasks that are dependent on touch. Implicating altered excitation-transcription coupling in SCN2A-related disorders would reveal a downstream point of convergence with other neurodevelopmental disorders and may suggest strategies for interventions focused on shared downstream targets.