I recently finished my MD-PhD in neuroscience at Baylor College of Medicine, working in the Smirnakis lab in close collaboration with Huda Zoghbi’s lab. I am now finishing my projects as a post-doc in the Smirnakis lab. The main thrust of my thesis work has been to explorethe role of altered synaptic stability and plasticity in autism pathophysiology. Imaging in vivo learning-associated dendritic spine plasticity in motor cortex of the mouse model of MECP2-duplication syndrome, we showed that increased formation and stabilization of clusters of dendritic spines on corticospinal neurons correlated with mouse’s enhanced motor learning phenotype. Moreover, Ras-MAPK signaling, known to drive clusters synaptic plasticity, was increased specifically during learning in these mice, and normalizing Ras-MAPK signaling with a pharmacological inhibitor normalized both enhanced learning and increased clustered spine stabilization in these animals. In a follow-up study I found evidence that presynaptic boutons of L5 pyramidal neuron axons projecting to layer 1 of motor cortex had decreased plasticity in MECP2-duplication mice, revealing further evidence for increased synaptic stability in these animals. Our findings of altered synaptic stability in this mouse model suggests that the prominent behavioral inflexibility and at times savant-like ability seen in autism could arise from an abnormal imbalance in favor of synaptic stability. I am also using chronic in vivo calcium imaging with GCaMP6 to study neural ensemble activity in motor cortex, visual cortex, and hippocampus of mouse models of MeCP2 disorders, in close collaboration with Hui Lu, previously a post-doc in the Zoghbi lab, now a professor at George Washington university. I plan to pursue research track residency training in psychiatry, and in the future I’m interested in studying the neural mechanisms underlying “deautomatization” through mindfulness, the weakening and elimination of habits by mindfulness meditation.
Jose A. Fernandez Leon Fellenz
Dr. Fernandez Leon Fellenz received the B.S., MSc. and Ph.D. degrees in Systems Engineering/Computer Science from the National University of Central Buenos Aires, Argentina, and a D.Phil. (Ph.D.) in Cognitive Science/Computational Neuroscience from the University of Sussex, UK. Since 2011, he has been working as Research Fellow/Postdoc Associate in the Systems Neuroscience field at the University of Texas-Houston Medical School, and Baylor College of Medicine in Houston, Texas (USA). He became Research Fellow at the Brigham and W omen’s Hospital, and Harvard Medical School to do research in Dr. Smirnakis’ Lab. His current interest is to understand how neurons encode (visual) information through robust, yet adaptive mechanisms and how these mechanisms become less functional and disrupted in autism.
Dr. Francesca Fortenbaugh received her B.S. in Mathematics and Psychology from the University of San Francisco (2004) and her Ph.D. in Psychology from the University of California, Berkeley (2012). For the last three years, she has worked as a postdoctoral research fellow at the Department of Veterans Affairs, Boston Healthcare System and Department of Psychiatry, Harvard Medical School. She has recently joined the Smirnakis Lab as a Research Fellow. Dr. Fortenbaugh’s research interests are in studying space perception and visual attention utilizing psychophysical and fMRI, and understanding how these processes are disrupted in various clinical populations (e.g, visual fields loss, visual neglect, PTSD, TBI).
Dr. Yuan Gao received her B.Eng in Biomedical Engineering from Southeast University, China, and her Ph.D in Neuroscience from Case Western Reserve University. She had her postdoctoral training in the Cleveland Clinic Foundation and Boston University with a focus on studying the neural bases of sensory perception. As a research scientist in the Smirnakis Lab, Dr. Gao’s research goal is to understand the mechanism underlying motor learning at both cellular and system levels. In particular, her focus is to compare the functional connectivity in the primary motor cortex (M1) between wide type and MECP2-duplication syndrome mice.
Dr. Zhaozhe Hao received her B.S in Biological Science in Nankai University, Tianjin, China, and her Ph.D. degree in Cellular and Behavioral Neurobiology from the University of Oklahoma, Norman, OK, US. She joined the Smirnakis Lab as a postdoctoral fellow to study the neuronal mechanism of Epilepsy.
Dr. Sangkyun Lee earned his Ph. D. degree and post-doc training in the field of human fMRI from International Max-Planck Research School, University of Tuebingen, Germany. Since then, he moved to Smirnakis Lab to study visual information processing in mouse visual cortex by using two-photon calcium imaging. His recent interest is to understand how neural ensembles encode visual information robustly despite of large fluctuations of neuronal activity and how the stimulus information is transmitted through columnar structures.
Dr. Jochen Meyer’s primary research interests are centered around furthering our understanding of the underlying cortical cellular and network defects in diseases like epilepsy and autism. Currently I am studying generalized absence epilepsy as well as focal, injury-induced epilepsy using techniques such as two-photon imaging, in vivo patch-clamp recordings and EEG in mice. We use the stargazer mouse model to study absence epilepsy, a common childhood form of the disease (https://youtu.be/JiD5-0dJsy4). Open questions are what role the different cortical layers and cell types, especially inhibitory interneurons, play in the initiation and maintenance of seizures, and which elements of the cortical circuitry could be targeted for novel therapeutic interventions. This project is carried out in close collaboration with Dr. Atul Maheshwari and Dr. Jeff Noebels, Baylor College of Medicine. The focal epilepsy study is based on a toxin-induced brain injury model that generates epilepsy over time. In these animals we follow the same groups of neurons over several months using chronic cranial windows to correlate calcium activity from larger numbers of neurons with epileptogenesis on the
EEG. My broader interests, which are based in previous work, cover neuronal network function in the cortex in general, in particular in the visual system. Specifically, I am studying how the activity of single neurons in the visual cortex influences the activity of the local neighborhood (https://youtu.be/dTd6o8R7FGc). This study is carried out in collaboration with Dr. Peyman Golshani, UCLA.
My main interest is the input-output function of pyramidal neurons in neocortex. I adopted the idea from lesion and focal brain inactivation studies to test how a pyramidal neuron in primary visual cortex integrates different dendritic inputs to compute visual information such as orientation selectivity and receptive field property. This allows us to causally test the role of apical and basal dendrite inputs to the visual stimulus selectivity of V1 neurons.