Assistant Professor of NeurobiologyLab Homepage: http://mcb.berkeley.edu/labs2/bateup/
Neurons dynamically modulate their synaptic inputs in a variety of ways to facilitate learning and storage of new information. At the same time, specialized mechanisms are in place to maintain excitability and firing within a bounded range to preserve balanced activity in neural circuits. The careful integration of these processes allows neurons to maintain homeostasis in the face of constant change. Notably, alterations in this delicate balance are thought to contribute to the manifestations of neurological and psychiatric disease. The goal of my laboratory is to understand the molecular mechanisms by which neurons modulate synaptic, neuronal, and network excitability. In particular, we are interested in how mutations in genes associated with disorders such as epilepsy and autism lead to altered synapse and circuit function. To investigate this, we are taking a multi-disciplinary approach incorporating molecular, biochemical, imaging, electrophysiological, and behavioral analyses in mouse models and patient-derived human cells. Through this diversity of approaches we hope to understand how molecular events change cellular and network function to ultimately impact behavior.
Basal ganglia dysfunction in autism spectrum disorders
The basal ganglia are a group of sub-cortical brain structures responsible for integrating sensory and motivational information to select and learn appropriate actions. We are studying how dysfunciton of the basal ganglia contributes to the behavioral manifestations of autism spectrum disorder (ASD). To investigate this, we use slice electrophysiology and behavior tasks in genetic mouse models of ASD to determine the relevant circuits, cells and synapses that may be comprimised in autism.
Genetically defined human neuron models of neurodevelopmental disorders
Recent advances in cellular reprograming and genome editing have endabled the generation of genetically engineered human cells for in vitro disease modeling. We are leveraging these approaches to generate a human neuronal model for the neurodevelopmental disorder Tuberous Sclerosis Complex (TSC), caused by mutations in the mTOR regulators TSC1 and TSC2. Our goal is to determine how mutations in the TSC genes impact human neuronal development and function.
Unraveling the complexity of neuronal mTOR signaling
The mTOR pathway is a central signaling hub that integrates intra- and extracellular signals to control processes related to cell growth and metabolism. Mutations in components of the mTOR pathway lead to syndromic neurodevelopmental disroders including TSC, which are often associated with ASD, epilepsy, and intellectual disability. It is not well understood how deregulated mTOR activity leads to neurological and psychiatric dysfunction. To investigate this, we use molecular profiling and biochemical approaches in mouse and human neurons to define the up- and down-stream components of the mTOR pathway. In addition, we are using imaging and electrophysiology to determine the functional impact of mTOR signaling perturbations, and test approaches to restore balanced mTOR activity in the context of disease.
Blair, J.D., Bateup, H.S., and Hockemeyer, D.F. (2016) Establishment of Genome-edited Human Pluripotent Stem Cell Lines: From Targeting to Isolation. J Vis Exp, Feb 2;(108):e53583. doi: 10.3791/53583.
Bateup, H.S., Denefrio, C.L., Johnson, C.A., Saulnier, J.L., and Sabatini, B.L. (2013) Temporal dynamics of a homeostatic pathway controlling neural network activity. Frontiers in Molecular Neuroscience, 6(28). doi: 10.3389/fnmol.2013.00028.
Bateup, H.S., Johnson, C.A., Denefrio, C.L., Saulnier, J.L., Kornacker, K., and Sabatini, B.L. (2013) Excitatory/Inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of Tuberous Sclerosis. Neuron, 78(3), 510-22.
Bateup, H.S., Takasaki, K.T., Saulnier, J.L., Denefrio, C.L., and Sabatini, B.L. (2011) Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. Journal of Neuroscience, 31(24), 8862-9.
Bateup, H.S., Santini E., Shen, W., Birnbaum, S., Valjent, E., Surmeier, D.J., Fisone, G., Nestler, E.J., and Greengard, P. (2010) Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors. PNAS, 107(33), 14845-50.
Bateup, H.S., Svenningsson, P., Kuroiwa, M., Gong, S., Nishi, A., Heintz, N., and Greengard, P. (2008) Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs. Nature Neuroscience, 11(8), 932-9.
Photo credit: Mark Hanson at Mark Joseph Studios.
Last Updated 2016-06-28