We have all had various experiences that have had a significant effect on who we are and how we act. Whether it was the childhood memory we will never forget, or the friendships we formed throughout school, our experiences definitely shape us. In a similar fashion, the neural connections within our brain change in response to experience. Just like when someone makes an impression in clay, our brains’ circuitry changes in response to new experiences.
This idea is referred to as “synaptic plasticity” and is a major focus of the Calakos lab, where I am working this summer. The lab focuses on how experience influences behavior, but also how in neurological conditions, the mechanisms of synaptic plasticity can go awry. More specifically, I am focusing on the condition of dystonia, which is a movement disorder in which muscles may contract uncontrollably and is the third most common movement disorder.
Past research within the lab has shown that there is a specific protein pathway known as eIF2alpha which is associated with synaptic plasticity and may be correlated with dystonia. Think of this protein pathway like a set of instructions that helps regulate our cells. This pathway typically responds when cells are experiencing high stress. It has been hypothesized that in dystonia, this pathway becomes dysregulated early on in development.
However, it remains uncertain whether and when targeting eIF2α signaling can improve dystonia. It is also important to determine exactly where in the brain selective vulnerability to altered eIF2α signaling occurs. Therefore, for my research project, I will be using western blot to determine if there is a dysregulation in eIF2alpha in a mouse model of dystonia compared to their littermate controls. I will analyze the brain tissue from mice for expression of eIF2alpha at various time-points throughout development including the day of birth, 5 days after birth, 14 days after birth, and 21 days after birth to determine if there is a period of susceptibility in which pathway dysregulation occurs. I will be analyzing four main brain regions: midbrain, striatum, cerebellum and cortex, regions previously implicated in dystonia, to determine if there is a specific brain region in which the pathway’s dysregulation is most predominant. I feel that my experiences working in this lab on this project will definitely shape my future decisions and maybe even change a few of my neural connections along the way.