Project Summary / Abstract
Research project: The human brain is characterized by dense neuronal connectivity, protracted maturation, and
unique circuit architecture. These features are thought to be critical for our higher cognitive functions, but may
also uniquely contribute to the pathology of neuropsychiatric and neurodevelopmental disorders in humans.
However, how these human-specific traits of neuronal connectivity affect the function of neuronal circuits remains
unknown. Interestingly, the candidate’s rich preliminary work shows that the human-specific gene SRGAP2C
induces human-specific traits in neuronal circuit organization in mice. By studying SRGAP2C and building on
these findings, the candidate will leverage this unique opportunity to investigate the yet unknown impact of
human-specific gene expression on neuronal circuit function. The candidate will train to use wide-field optical
mapping, 2-photon microscopy, and optogenetics, to investigate in vivo how SRGAP2C affects circuit function
cortex-wide and at a cellular level. Finally, using a sensory-discrimination task, the candidate will test whether
SRGAP2C-mediated changes in circuit architecture affect behavior and learning.
Candidate and career goals: The candidate has a strong background in molecular and cellular neurobiology,
having spent his PhD studying the mechanisms underlying neuronal circuit formation. Dr. Schmidt has a deep
interest in understanding the mechanisms that shape neuronal circuit architecture. His long-term career goal is
to establish an independent laboratory focused on uncovering the relationship between neuronal circuit structure,
function, and behavior. He is particularly interested in determining the mechanisms underlying unique aspects
of human brain development and evolution. His unpublished work has already revealed remarkable effects of
the human-specific genetic modifier SRGAP2C on neuronal circuit organization. The goal of this proposal is to
uncover the role SRGAP2C plays in regulating cortical circuit function and behavioral performance.
Career development plan: The candidate will work with two internationally renowned mentors, Drs. Franck
Polleux and Rui Costa. Dr. Polleux is an expert in using genetic, molecular, cellular, and imaging techniques to
study cortical connectivity. Dr. Costa is an expert in combining in vivo microscopy and optogenetics with
behavioral approaches. In addition, the candidate has assembled a unique team of collaborators, consisting of
Drs. Elizabeth Hillman, Randy Bruno, and Darcy Peterka, who will be instrumental in training him in the use of
in vivo microscopy and setting up the sensory-discrimination task. The candidate’s excellent mentors and
collaborators will advise and guide him in both his research and his transition towards an independent career.
As part of the neuroscience community of Columbia University, Dr. Schmidt will work within an exceptional
research environment. He will benefit from excellent facilities and all needed equipment for the proposed
research. Moreover, he will work in a highly supportive training setting that offers extensive opportunities to
present and receive feedback on his research, and resources for transitioning to an independent research career.