Grant: Master's Award: Canada Graduate Scholarships

This project investigates sensory processing dysfunction in a mouse model of Rett Syndrome (RTT). RTT is a neurodevelopmental disorder with complex symptoms that culminate in requiring full-time care. RTT is caused by mutations to a gene called MECP2 that is pivotal for wiring up and maintaining the highways of communication between neurons in the brain. Without MECP2, these highways – called neural networks – become inefficient, leading to deficits in learning and memory, though how this happens remains a mystery. This project seeks to help answer this question. The MECP2 gene is found on the X chromosome, and the RTT mutations occur almost exclusively in male sperm. Since father’s do not pass an X chromosome to male offspring, RTT predominantly affects females. In females, all cells – including neurons – have two X chromosomes, but only 1 of the chromosomes is active. The other X chromosome gets silenced in a process called X inactivation. Due to this process, female RTT patients (and mice) have a mixture of cells that either have the mutated X chromosome active or the non-mutated X chromosome active. This means that the neural networks of RTT patients and mice are made of a mixture of mutated and non-mutated neurons. This project will use state of the art two-photon calcium imaging to compare how these two different neuron types are functioning in a neural network that processes touch sensations from the hindlimb. The neural networks of mice that don’t have the mutation remember past touch sensations for an hour or more, while RTT model mice forget within 15 minutes. We seek to understand if all neurons within this network forget, or if it’s just the mutated neurons. This is important because future therapies need to be compatible in the mixed neuron environment.