One of the most remarkable things that develops during human childhood and teenage years is the perception, expression, and regulation of emotions. This is also a time when emotional disorders like anxiety and depression often emerge. Many brain regions work together to orchestrate emotional memories and responses, and these structures grow significantly in children. Determining the cellular basis for this development and processes that go awry in neuropsychiatric illness is the primary focus of our laboratory.
Neurons and other cells continue to develop throughout our whole lives, and some brain regions and types of neurons take much longer to develop than others. In the human brain there are multiple populations of late-developing neurons that grow and mature significantly during adolescence. The developmental factors that lead to a different timescale for the growth of these cells are not known, and a longer period of development may make these neurons particularly susceptible to environmental influences like stress or enrichment.
Our lab has two primary research aims: 1) to study human neurodevelopment in the temporal lobe, which includes structures like the amygdala (governing fear, anxiety, and social behaviors), the hippocampus (memory storage) and the entorhinal cortex (spatial memory). 2) to learn about developmental processes that direct neuron structural plasticity and growth in similar regions of the adolescent mouse brain.
Sorrells S.F., Paredes M.F., Zhang Z., Kang G., Pastor-Alonso O., Biagiotti S., Page C.E., Sandoval K., Knox A., Connolly A., Huang E.J., Garcia-Verdugo J.M., Oldham M.C., Yang Z., Alvarez-Buylla A. Positive controls in adults and children support that very few, if any, new neurons are born in the adult human hippocampus. J Neurosci. 2021 Mar 24;41(12):2554-2565. doi: 10.1523/JNEUROSCI.0676-20.2020.
Ellis J.K., Sorrells S.F., Mikhailova S., Chavali M., Chang S., Sabeur K., Mcquillen P., Rowitch D.H. Ferret brain possesses young interneuron collections equivalent to human postnatal migratory streams. J Comp Neurol. (2019) May 3. doi: 10.1002/cne.24711.
Sorrells S.F., Paredes M.F., Velmeshev D., Herranz-Pérez V., Sandoval K., Mayer S., Chang E.F., Insausti R., Kriegstein A.R., Rubenstein J.L., Manuel Garcia-Verdugo J., Huang E.J., Alvarez-Buylla A. Immature excitatory neurons develop during adolescence in the human amygdala. Nat Commun. 2019 Jun 21;10(1):2748. doi: 10.1038/s41467-019-10765-1.
Paredes M.F.*, Sorrells S.F.*, Cebrian-Silla A., Sandoval K., Qi D., Kelley K.W., James D., Mayer S., Chang J., Auguste K.I., Chang E.F., Gutierrez Martin A.J., Kriegstein A.R., Mathern G.W., Oldham M.C., Huang E.J., Garcia-Verdugo J.M., Yang Z., Alvarez-Buylla A. Does Adult Neurogenesis Persist in the Human Hippocampus? (2018) Cell Stem Cell. Dec 6;23(6):780-781.
Raju C.S., Spatazza J., Stanco A., Larimer P., Sorrells S.F., Kelley K.W., Nicholas C.R., Paredes M.F., Lui J.H., Hasenstaub A.R., Kriegstein A.R., Alvarez-Buylla A., Rubenstein J.L., Oldham M.C. Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity. Cereb Cortex. 2018. Jun 1;28(6):1946-1958.
Sorrells S.F.*, Paredes M.F.*, Cebrian-Silla A., Sandoval K., Qi D., Kelley K.W., James D., Mayer S., Chang J., Auguste K.I., Chang E.F., Gutierrez A.J., Kriegstein A.R., Mathern G.W., Oldham M.C., Huang E.J., Garcia-Verdugo J.M., Yang Z., Alvarez-Buylla A. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018. Mar 15;555(7696):377-381.
Paredes M.F.*, Sorrells, S.F.*, Garcia-Verdugo, J.M., Alvarez-Buylla, A. Brain size and limits to adult neurogenesis. J Comp Neurol. 524(3) 646-64. (2016).