Position Title
Professor of Neurobiology, Physiology and Behavior
- Core Faculty, Center for Neuroscience
Development and Plasticity of Neural Circuits
Research Summary
The goal of our research is to understand at the cellular and molecular level how synaptic connections form during development, how they are modified during learning, and how they are altered in disease. Most of the excitatory synaptic connections in the cerebral cortex occur on dendritic spines, tiny protrusions that extend from the neuronal dendritic membrane. Changes in the strength of excitatory synaptic connections are tightly coupled with changes in the structure of dendritic spines, and those structural changes are thought to impart long-term stability to the circuit modifications that occur during learning. Furthermore, spine motility, driven by actin dynamics, is thought to allow the postsynaptic neuron to explore and sample presynaptic partners, facilitating learning.
The identification and characterization of the molecules and mechanisms that control spine growth and stabilization will be a crucial step toward understanding the formation and plasticity of cortical circuits. Our approach to this problem combines time-lapse imaging to observe nascent spine formation with molecular manipulations of synaptic proteins to decipher their roles in the growth of dendritic spines and synapses. In addition, we use electrophysiological measurements in combination with two-photon uncaging of glutamate to examine the function of nascent synapses at the single synapse level and to probe the role of competitive interactions between neighboring synapses on local dendritic segments in regulating synaptic plasticity.
Highlighted Research Articles
Petshow S, Coblentz A, Hamilton AM, Sarkar D, Anisimova M, Flores JC, Zito K (2025) Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization. Science Advances 11(13):eadp5782.
Flores JC, Sarkar D, Zito K (2025) A synapse-specific refractory period for plasticity at individual dendritic spines. Proc Natl Acad Sci U S A. 122(2):e2410433122.
*Claiborne N, *Anisimova M, Zito K (2024) Activity-Dependent Stabilization of Nascent Dendritic Spines Requires Nonenzymatic CaMKIIα Function. J Neurosci. 44(2):e1393222023.
*Stein IS, *Park DK, Claiborne N, Zito K (2020) Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines. Cell Reports 34: 108664.
Lambert JT, Hill TC, Culp JH, Zito K. (2017) Protracted and asynchronous accumulation of PSD95-family MAGUKs during maturation of nascent dendritic spines. Dev Neurobiology 77: 1161-74.
Oh WC, Parajuli LK, Zito K (2015) Local heterosynaptic plasticity of dendritic spines on hippocampal CA1 neurons. Cell Reports 10:162-169.
Hill TC, Zito K (2013) LTP-induced long-term stabilization of nascent dendritic spines. J Neurosci. 33:678-86.
Hamilton AM, Oh WC, Vega-Ramirez H, Stein IS, Hell JW, Patrick GN & Zito K (2012) Activity-dependent growth of nascent dendritic spines is regulated by the the proteasome. Neuron 74: 1023-30.
Zito K, Scheuss V, Knott G, Hill TC & Svoboda K (2009) Rapid functional maturation of nascent dendritic spines. Neuron 61: 247-258.
Highlighted Review Articles and Book Chapters
Park DK, Stein IS, Zito K (2022) Ion flux-independent NMDA receptor signaling. Neuropharmacology, 210: 109019.
Stein IS, Hill TC, Oh WC, Parajuli LK, Zito K (2019) Probing the structural and functional plasticity of dendritic spines using two-photon glutamate uncaging. In: Multiphoton Microscopy, Hartvelt E (ed.), Springer Nature, pp 65-85.
Stein IS, Zito K. (2019) Dendritic Spine Elimination: Molecular Mechanisms and Implications. The Neuroscientist, 25: 27-47.
DeBello W, Zito K (2017) Within a Spine & Reach. In: The Rewiring Brain, Part IV: Structural Plasticity and Learning and Memory, vanOoyen A, (ed), Elsevier Academic Press, San Diego, CA, pp. 295-317.
Hamilton AM & Zito K (2011) A thorny question: the role of spine morphogenesis in adaptive plasticity. In Cerebral Plasticity: New Perspectives, Chalupa LM, Berardi N, Caleo M, Galli-Resta L, Pizzorusso T (eds.), MIT Press, Cambridge MA, pp. 129-137.
Zito K & Scheuss V (2009) NMDA receptor function and physiological modulation. In: Squire LR (ed.) Encyclopedia of Neuroscience, volume 6, pp. 1157-1164, Oxford: Academic Press.
Woods G, Zito K. (2008) Preparation of gene gun bullets and biolistic transfection of neurons in slice culture. Journal of Visualized Experiments, 12: doi: 10.3791/675.
Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology (BMCDB) Graduate Group
- Molecular, Cellular and Integrative Physiology (MCIP) Graduate Group
- Neuroscience (NSC) Graduate Group
- Fellow of the American Association for the Advancement of Science
- UC Davis Chancellor's Award
- Outstanding Graduate Mentor in Neuroscience Award
- National Science Foundation CAREER Award
- NARSAD Young Investigator Award
- Burroughs Wellcome Fund Career Award in the Biomedical Sciences