Cells, Circuits, & Systems

The Cells, Circuits and Systems Analysis Core provides essential services to the IDDRC community to foster research into the functional consequences of developmental disorders. The Core consists of two main components: 1) Neurophysiological Assessment and 2) Cellular and Organoid Modeling. 

The need for physiological assessments was generated by IDDRC faculty who required electrophysiological studies beyond collaborations. These electrophysiological assessments consist of experiments performed in brain slices, acutely isolated neurons, in cultures or in vivo, providing a functional analysis of changes in neurons, local circuits and microcircuits induced primarily by genetic alterations in cellular, mouse or rat models. The Core will continue to assist Investigators with functional analysis at the cellular, circuit, and systems level using state-of-the-art electrophysiology, optogenetic recording methods both in in vitro and in vivo preparations and miniscopes. 

Recent advances in both genomic and stem cell technologies, particularly human embryonic and induced pluripotent stem cells (hESC and hiPSC), have opened the door to new approaches in IDD research based on human cells.  A significant challenge remains to translate this promise into new discoveries about the basis of IDD and therapies. The second objective of this Core will be to facilitate this process by assisting IDDRC investigators to produce, propagate, and differentiate hESC and hiPSC, (collectively hPSC) into neural and glial cell types of interest as well as brain organoids to create in vitro models of IDD. Another function of the Core is to work with investigators and molecular screening resources available at UCLA to harness the potential of these in vitro models for drug discovery. 

The Core is directed by Dr. Kornblum who has over 40 years’ experience in the study of developmental neurobiology and is well known for his expertise in mammalian neural cell culture, including the culture of neural and pluripotent stem cells. As Core co-Director since 2015 and Director since 2016 Dr. Kornblum has overseen a great expansion in cell culture capacity, overseeing the building and refurbishing Core space in the Laurie and Steven C. Gordon Neuroscience Research Building (Gordon NRB), the primary home of the IDDRC. 

The Neurophysiological Assessment component is co-Directed by Dr. Levine, a Distinguished Professor of Psychiatry and Biobehavioral Sciences and a well-known international authority on electrophysiological assessment of developmental, neurodegenerative and neurological disorders and Dr. Carlos Cepeda who has worked with Dr. Levine for over 30 years. Dr. Cepeda is an Adjunct Professor and Research Physiologist with expertise in all aspects of recording from single cells and microcircuits in vitro, EEG recording in vivo, optogenetics, and most recently he has been instrumental in developing the miniscope technology (see Core D) in the lab. His experience working with genetically-engineered mice and in mouse models of developmental, neurodegenerative and psychiatric disorders has been instrumental to the success of the previous IDDRC Electrophysiology Cores. Drs. Levine and Cepeda meet with all prospective Neurophysiological Assessment Core users to design the experiments and Dr. Cepeda coordinates the day-to-day activities necessary to perform the experiments and/or provide instruction in methodology. 

The Cellular and Organoid Modeling component will be co-directed by Drs. Bennett Novitch and Harley Kornblum, longtime colleagues and collaborators. Dr. Novitch is a Professor in the Department of Neurobiology. He has over 22 years of experience in the field of neurodevelopmental research, focusing on the molecular mechanisms that direct the formation of different classes of neurons and glial cells in the developing spinal cord and brain using animal models and both mouse and hESC and hiPSC. Dr. Novitch is a leading authority in hPSC-based modeling including brain organoid technologies.