Melisa Sencer: Identifying the Cellular Changes in Fragile X Syndrome

In the field of neuroscience, researching sensory systems is all the rage. This is due to the fascinating and crucial role our senses play in interacting with the world around us. Imagine the countless ways we use our auditory system daily. The auditory system not only allows us to hear sounds but also helps us to interpret emotional cues and understand the context of situations. However, for those with Fragile X Syndrome (FXS), everyday noise environments can be overstimulating and stressful. FXS is one of the leading known causes of inherited intellectual disability and is relatively common in individuals with Autism Spectrum Disorder (ASD). My name is Melisa Sencer, and I am thrilled to be the recipient of the IDEA Grant for the 2023 summer semester. My goal for this summer is to continue my research studying the cellular and molecular components of FXS.

Melisa Sencer, Junior, Cell and Molecular Neuroscience

This summer, I’ll spend a lot of time in Dr. Wang’s lab performing wet lab experiments. Specifically, I’ll be focusing on the Superior Olivary Complex (SOC), which is a crucial part of the auditory pathway responsible for integrating and processing sound from both ears. Within this complex lies the Medial Nucleus of the Trapezoid Body (MNTB), a small but mighty group of cells that sends inhibitory signals to other nuclei in the area. Dysfunction or damage to the MNTB nuclei has been linked to deficits in sound localization and auditory processing in mice models, which is particularly relevant for individuals with FXS who experience sensory overload in noisy environments.

Intracellular filling, is a technique sometimes used in the neuroscience field to study individual neurons. This neuroscience method involves using a very thin electrode that is made in our lab to find a neuron. Once a cell is found, you can use the electrode to inject a dye. The dye then fills the neuron and highlights its morphology, allowing researchers to study the structure and function of the neuron in detail. This technique can also be used to record electrical activity from the neuron which helps us to know we have located a cell. Single-cell filling is a valuable tool for understanding the organization and function of neural circuits. 

Microscopic device used for cell filling.

However, single-cell filling is no easy feat! It requires skill, patience, and specialized equipment to get accurate and reproducible results. During the past semesters, I began to learn the complex intracellular procedure. Since then, I have identified protocol improvements that will lead to a more successful and reproducible procedure. To characterize cells produced from brain slices, biocytin is used to fill them while simultaneously recording the tissue voltage using an electrode. The tissue is kept alive by maintaining it in a calcium and potassium solution with a stable oxygen flow. Antibody staining is then performed to study the cells’ morphology and neurochemistry. To achieve the best results, the tissue is sectioned to 100μm or less before antibody staining. By working on these promising procedure developments, we hope to understand and create a better procedure for cell filling and also deduce more information on the MNTB region.

Furthermore, I plan to experiment with new methods for preparing brain tissues and determining the best coordinates for locating neurons in the Medial Nucleus of the Trapezoid Body (MNTB). I will then collect data by performing cell filling and tissue processing, anticipating filling 3-5 cells per week for a sample size of 18-30 cells. Finally, I will use a software called Neurolucida to reconstruct the 3D connectivity of the cells and compare quantitative analyses between neurons of wildtype and Fmr1 KO mice.

My journey researching Fragile X syndrome has been transformative, providing me with a comprehensive understanding of the neurobiological mechanisms underlying the disorder. However, as a pre-med student with a passion for clinical practice, my goals extend beyond the lab. My goal is to one day bridge the gap between research and treatment by using proven data to develop innovative therapies and improve the quality of life for my future patients and those living with FXS. This project has deepened my understanding of neuroscience research and brain pathology. It has also ignited a passion for applying research to clinical settings. Overall, I am truly grateful for the opportunity this grant has given me to work alongside my exceptional research mentor Dr. Yuan Wang, continue my research, and contribute to the growing body of knowledge on Fragile X syndrome and the auditory pathway. I’m filled with anticipation and can’t wait for the exciting developments that lie ahead for my project and me over the summer!

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