Unraveling Cognitive Mysteries: Dendritic Spine Morphology in Pitt-Hopkins Syndrome (PTHS) (2024)
Undergraduate: Dan Tsuma
Faculty Advisor: Alain Burette
Department: Cell Biology and Physiology
Pitt-Hopkins Syndrome (PTHS), a rare neurodevelopmental disorder
resulting from TCF4 gene haploinsufficiency, leads to profound cognitive
challenges, including intellectual disability and learning and memory
deficits. Understanding the neural basis of these cognitive impairments is
essential for advancing therapies. Dendritic spines, minute protrusions on
neurons, are key players in synaptic connections and memory formation,
making their morphology a vital focus. Changes in spine characteristics are
linked to various neurological disorders, including autism spectrum
disorder. This research explores how TCF4 haploinsufficiency in PTHS
may affect dendritic spine morphology, specifically in the hippocampus, but
also in the cortex, and its role in learning and memory deficits. By
comparing dendritic spine characteristics between a novel PTHS mouse
model, which exhibits TCF4 haploinsufficiency, and wildtype mice, we aim
to test the hypothesis that TCF4 haploinsufficiency leads to a reduction in
spine number and concurrent alterations in their size and shape. Through
Golgi staining, widefield microscopy, and future image analysis, this
investigation lays the groundwork to elucidate the intricate relationship
between dendritic spine structure and cognitive function in PTHS,
potentially paving the way for therapeutic advancements and improved
quality of life for affected individuals.