Dr. Huber obtained her undergraduate degree in Biology and Psychology at Stephen F. Austin State University. In 1995, she earned a Ph.D. in Neurobiology from the University of Texas Health Science Center at Houston, where she worked in the laboratory of Dr. Paul Kelly studying biochemical mechanisms of synaptic plasticity. Dr. Huber continued her work on synaptic plasticity as a postdoc with Dr. Mark Bear at Brown University. She joined the faculty of UT Southwestern in 2001.
The brain is estimated to be made up of one hundred billion neurons which are connected by 100 trillion synapses. Synapses are the major way in which neurons communicate and therefore the biological basis for brain function and behavior. Synapses are dynamic and changes in their structure, function and number (collectively termed plasticity) occur during learning, mediate memories, and sculpt the development of our sensory experiences. Understanding how synaptic plasticity occurs and how stable synaptic properties maintain memories throughout a lifetime is an ultimate goal in neuroscience.
One major focus of the Huber lab is to understand the cellular and molecular mechanisms that mediate synaptic plasticity. A major mechanism by which synaptic plasticity occurs is through the localized and synaptic synthesis of new proteins. Much of our work is focused on studying a form of synaptic weakening or depression which relies on very rapid, protein synthesis at synapses. Long-term synaptic depression or LTD is induced by activation of Gq coupled receptors, such as the metabotropic glutamate receptors (mGluRs). By studying the mechanisms mGluR-dependent LTD, we can address major questions in the field such as: How does synaptic activity regulate rapid protein synthesis at synapses? What are the proteins which are synthesized in dendrites and how do they affect synapse function? What role does synaptic or dendritic protein synthesis play in the nervous system and how do alterations or dysfunction of the dendritic protein synthesis machinery contribute to neurological disease?
Altered synapse structure and dysfunction is thought to be the origin of many neurological diseases. Motivated by our basic research findings, we discovered altered synaptic plasticity and function in the mouse model of mental retardation and autism, Fragile X Syndrome. Therefore, another aim of the lab is to identify and understand how alterations in synaptic function and connectivity lead to mental retardation and autism. Specifically, we find that LTD is enhanced and abnormally regulated in a mouse model of human mental retardation, Fragile X Syndrome. Fragile X Syndrome is caused by loss of function mutations in an RNA binding protein called Fragile X Mental Retardation Protein (FMRP), which is an RNA binding protein and regulates protein synthesis at synapses. A third goal of the Huber lab is to determine how RNA binding proteins, such as FMRP, regulate dendritic protein synthesis and, in turn, synapse function. To address these research questions we use a multi-disciplined approach including electrophysiology, imaging, and biochemical methods in the hippocampus and neocortex, major brain structures implicated in human cognition. Work is our laboratory is supported by grants from the NIH-NINDS, the FRAXA Research and Autism Speaks Foundations.
Waung, M.W., Pfeiffer, B.E., Nosyreva, E.D., Ronesi, J.A. and Huber, K.M. (2008) Rapid translation of Arc/Arg3.1 selectively mediates mGluR dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron, 59(1):84-97.
Gibson, J.R., Bartley, A.F., Hays, S. and Huber, K.M. (2008) An imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of Fragile X Syndrome. Journal of Neurophysiology, 100(5):2615-26.
Ronesi, J.A. and Huber, K.M. (2008) Homer interactions are necessary for mGluR-induced long-term depression and translational activation. Journal of Neuroscience, 28(2):543-7.
Volk, L. J., Pfeiffer, B.E, Gibson, J.R. and Huber, K.M. (2007) Multiple Gq-coupled receptors converge upon a common protein synthesis- dependent LTD that is affected in Fragile X syndrome mental retardation. Journal of Neuroscience, 27(43):11624-34.
Pfeiffer, B.E. and Huber, K.M. (2007) Fragile X Mental Retardation Protein induces synapse loss through acute postsynaptic translational regulation. Journal of Neuroscience, 27(12):3120-30. Highlighted in Nature Reviews Neuroscience, May 2007.
Gibson, J.R., Bartley, A. and Huber, K.M. (2006) A Role for the Subthreshold Currents ILeak and IH in the Homeostatic Control of Excitability in Neocortical Somatostatin-Positive Inhibitory Neurons Journal of Neurophysiology, 96(1):420-32.
Nosyreva E. N. and Huber K.M. (2006) Metabotropic glutamate receptor dependent long-term depression persists in the absence of protein synthesis in the mouse model of Fragile X Syndrome Journal of Neurophysiology, 95(5): 3291-5.
Volk, L, Daly, C.A. and Huber K.M. (2006) Differential roles for group 1 mGluR subtypes in induction and expression of chemically-induced hippocampal long-term depression. Journal of Neurophysiology, 95(4): 2427-38.
Nosyreva, E.N. and Huber, K.M. (2005) Developmental switch in mechanisms of hippocampal metabotropic glutamate receptor dependent synaptic plasticity. Journal of Neuroscience, 25(11): 2992-3001.
Gallagher, S.M.. Daly, C.A., Bear, M.F. and Huber, K.M. (2004) Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor -dependent long-term depression in hippocampal area CA1. Journal of Neuroscience, 24(20):4859-64.
Huber, K.M., Gallagher, S., Warren, S.T. and Bear, M.F. (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci., 99(11): 7746-7750.
Huber, K.M., Kayser, M.S. and M.F. Bear. (2000) Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent LTD. Science, 288(5469):1254-1257.
Ronesi J.R. and Huber, K.M. (2008) Metabotropic Glutamate Receptors and Fragile X Mental Retardation Protein: Partners in translational regulation at the synapse. Science Signaling, 1(5):pe6.
Pfeiffer, B.E. and Huber, K.M. (2006) Current advances in local protein synthesis and synaptic plasticity. Journal of Neuroscience, 26 (27): 7147-50.
Bear, M.F., Huber, K.M. and Warren, S.T. (2004) The mGluR theory of fragile X mental retardation. Trends in Neuroscience, 27(7):370-7.