Kristen Harris
- Professor
- Neuroscience
Contact Information
Research
Knowing the dimensions and connectivity of synapses is fundamental to understanding function. In the brain, more than 90% of synapses occur on dendritic spines. These tiny protrusions from the surface of dendrites measure about 1 micrometer in length. Dendritic spine structure is clearly important for normal brain function because when brain function is impaired, such as in conditions of mental retardation, epilepsy, and stroke, the dendritic spines are either gone, or have highly distorted shapes and sizes.
Our goal is to elucidate structural components involved in the cell biology of learning and memory. We study long-term potentiation (LTP) and its complement, long-term depression (LTD), in the developing and mature hippocampus because these phenomena have many of the physiological characteristics that are expected for learning and memory in the brain. Our working hypothesis is synaptic plasticity that serves to modify synapses in the creation of new memories competes with homeostatic mechanisms that serve to prevent saturation of synaptic strength and neuropathology. Our focus has been on dendritic spines because they are the major postsynaptic targets of excitatory axons throughout the brain and because their structure and composition serve both synaptic plasticity and stabilizing homeostatic mechanisms.
Research Areas
- Neuroscience
- Learning and Memory
Fields of Interest
- Electrophys, Optogenetics & Chemogenetics
- Cellular/Molecular/Structure
- Learning/Memory/Plasticity
Publications
2016 Smith HL, Bourne JN, Cao G, Chirillo MA, Ostroff LE, Watson DJ, Harris KM Mitochondrial support of persistent presynaptic vesicle mobilization with age-dependent synaptic growth after LTP. http://dx.doi.org/10.7554/eLife.15275. eLife 2016;5:e15275
2016 Watson DJ, Ostroff L, Cao G, Parker PH, Smith H, Harris KM LTP enhances synaptogenesis in the developing hippocampus. Hippocampus, 26(5):560-76.
2015 Bartol TM, Bromer C, Kinney JP, Chirillo MA, Bourne JN, Harris KM, Sejnowski TJ. Nanoconnectomic upper bound on the variability of synaptic plasticity. doi: 10.7554/eLife.10778. PMCID: PMC4737657 (Bartol, Harris, and Sejnowski, co-corresponding authors).
2015 Bartol TM, Keller DX, Kinney JP, Bajaj CL, Harris KM, Sejnowski TJ, Kennedy MB Computational reconstitution of spine calcium transients from individual proteins. Front. Synaptic Neuroscience doi:10.3389/fnsyn.2015.00017.
2015 Harris KM, Spacek J, Bell ME, Parker PH, Lindsey LF, Baden AD, Vogelstein JT, Burns R. A resource from 3D electron microscopy of hippocampal neuropil for user training and tool development. Scientific Data (Nature Publishing Group) 2:150046.
2015 Bailey CH, Kandel ER, Harris KM. Structural Components of Synaptic Plasticity and Memory Consolidation. Cold Spring Harb Perspect Biol. 2015 Jul 1;7(7). pii: a021758. doi: 10.1101/cshperspect.a021758.
2014 Bell ME, Bourne JN, Chirillo MA, Mendenhall JM, Kuwajima M, Harris KM. Dynamics of nascent and active zone ultrastructure as synapses enlarge during long-term potentiation in mature hippocampus. J Comp Neurol. 522(17):3861-84. PMCID: PMC4167938.
2014 Cao G, Harris KM. Augmenting saturated LTP by broadly spaced episodes of theta-burst stimulation in hippocampal area CA1 of adult rats and mice. J Neurophysiol. 112(8):1916-24
2013 Kuwajima M, Mendenhall JM, Harris KM Large-volume reconstruction of brain tissue from high-resolution serial section images acquired by SEM-based scanning transmission electron microscopy. Methods Mol. Biol., 950:253-273.
2013 Kinney JP, Spacek J, Bartol TM, Bajaj CL, Harris KM Sejnowski TJ , Extracellular sheets and tunnels modulate glutamate diffusion in hippocampal neuropil., J. Comp. Neurology 521: 448-464
2012 Cui-Wang T, Hanus C, Cui T, Helton T, Bourne JN, Watson DJ, Harris KM and Ehlers MD Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites. Cell 148: 309-21
2012 Cao G and Harris KM. , Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat. , J Neurophysiol. 107: 902-12
2011 Bourne, J. N. and Harris, K. M. , Coordination of size and number of excitatory and inhibitory synapses results in a balanced structural plasticity along mature hippocampal CA1 dendrites during LTP., Hippocampus 21: 354-73
Awards
- Elected to the National Academy of Sciences in 2024