Schmidt Laboratory

We study how human-specific genes (HSGs) modify brain development and function, and how HSGs play a role in disease by altering the phenotypic expression of neurodevelopmental disorders. Our goal is to advance our insight into the mechanisms that shape the unique biological features of the human brain, and how these features are disturbed in neurodevelopmental disease.

Research:
We have previously shown how SRGAP2C, an HSG that modifies synaptic development, changes the structural and functional organization of cortical circuits, and improves learning. These findings highlight how synaptic development provides a molecular and cellular substrate through which the large-scale organization of cortical circuits and their functional properties can be modified, and behavioral performance can be enhanced.

Synaptic development has also been critically implicated in a number of neurodevelopmental diseases, including Autism Spectrum Disorder (ASD). However, while our work has shown that changes in synaptic development can directly impact the brain-wide organization and function of neuronal circuits, we currently know little about how the large-scale structure and function of neuronal circuits is affected in ASD and other neurodevelopmental disorders.

Our lab uses a combination of in vivo microscopy approaches (including 2-photon and wide-field imaging), neuronal circuit mapping techniques, and behavioral mapping to investigate how HSGs modify brain development and function, how impaired synaptic development impacts the structure and function of neuronal circuits, and how HSGs alter the phenotypic expression of disease. Together, this work will help elucidate how neuronal circuit structure and function forms the foundation for learning and cognition and lay the groundwork for studying how neuronal connectivity is impaired in neurodevelopmental disorders.

Team:
Director
Ewoud Schmidt, Ph.D.
Assistant Professor

Staff and Students
Taylor Anderson, BSc
Research Technician

Teresa Zhao, Ph.D.
Postdoctoral Fellow

Kayla Green, BSc
Graduate Student

Schmidt Laboratory Recent Publications (2020-current):
Schmidt ERE and Polleux F. Genetic mechanisms underlying the evolution of connectivity in the human cortex. Frontiers in Neural Circuits.
doi: https://doi.org/10.3389/fncir.2021.787164

Liu J, Mosti F, Zhao HT, Sotelo-Fonseca JE, Escobar-Tomlienovich CF, Lollis D, Musso CM, Mao Y, Massri AJ, Doll HM, Sousa AM, Wray GA, Schmidt E, Silver DL. A human-specific enhancer fine-tunes radial glia potency and corticogenesis. https://www.biorxiv.org/content/10.1101/2024.04.10.588953v1

Schmidt ERE, Zhao HT, Park JM, Dipoppa M*, Monsalve-Mercado MM*, Dahan JB, Rodgers CC, Lejeune A, Hillman EMC, Miller KD, Bruno RM, Polleux F (*contributed equally). A human-specific modifier of cortical connectivity and circuit function
Nature 599, 640-644. doi: https://doi.org/10.1038/s41586-021-04039-4

Brignani S*, Raj DDA*, Schmidt ERE, Dudukcu Ö, Adolfs Y, De Ruiter AA, Rybiczka-Tesulov M, Verhagen MG, Van der Meer C, Broekhoeven M, Moreno-Bravo JA, Grossouw LM, Dumontier E, Cloutier J-F, Chédotal A, Pasterkamp RJ (*contributed equally). Remotely produced and axon-derived Netrin-1 instructs GABAergic neuron migration and dopaminergic substantia nigra development in the ventral midbrain.
Neuron 107, 684-702. doi: https://doi.org/10.1016/j.neuron.2020.05.037

For more information on the work we do in our lab, please visit https://www.schmidtlab-neuro.com