Neurolab at Emory University

Axon development representing brain development research

Brain Wiring, Growth Cone Motility, Axon Guidance

We investigate directed cell motility in nerve cells, aiming to understand how developing axons extend and navigate to reach their specific target cells to form synaptic connections. We focus on the spatiotemporal signaling and cytoskeletal events that enable the motile tip of developing axons, the growth cone, to respond to environmental cues to reach their specific targets.

#Chemotaxis #Filopodia #Lamellipodia #Calcium signaling #Actin cytoskelon #Microtubules #Brain development

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Hippocampus representing synapse research

Hippocampal circuitry, Synapse, and Plasticity

Synaptic connections are plastic, undergoing short- and long-term remodeling during development, learning, and memory. We study the cytoskeletal regulation of synaptic structure, function, modification, and disruption in disease. Currently, we are exploring novel cytoskeletal mechanisms that regulate the structure and function of unique synapses of the tri-synaptic hippocampal circuitry.

#Dendritic spines #Synaptic plasticity #Actin binding proteins #Mossy fiber boutons #CA3-CA1 synapses #Super-resolution

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Abstract image representing neurodegeneration research

Neurodegeneration and Environmental Insults

Neurodegenerative diseases (e.g., AD) are more prevalent in aging populations. We use Drosophila as a model to study how environmental factors, such as mild head trauma, trigger and accelerate neurodegenerative diseases in aging individuals. We combine AI-driven tracking and analysis, as well as whole-brain imaging to explore the mechanisms behind age-related neurodegeneration.

#Alzheimer's #Brain concussion #Atrophy #Cortex #Machine learning #Sensorimotor

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Brain Wiring, Growth Cone Motility, Axon Guidance

Over a century ago, Ramon y Cajal made his landmark observations on the patterns of nerve process outgrowth and connectivity in developing brains and described the motile tip of each elongating axon, the growth cone, as the responsible unit for axon elongation and pathfinding to the target cells. Developing axons are guided to their targets by a variety of environmental cues, including long-range diffusible and short-range surface-bound molecules that can either attract or repel the axon. The presence of these guidance cues in temporal and spatial patterns enables the growth cone to navigate through the complex environment of the developing embryo to reach its correct target. We investigate the signaling pathways and cytoskeletal mechanisms that enable the growth cone to translate extracellular signals to directional movement during guidance.

Featured publications:

Hardin KR, Penas AB, Joubert S, Ye C, Myers KR, Zheng JQ. (2025). A critical role for the Fascin family of actin bundling proteins in axon development, brain wiring and function.Mol Cell Neurosci. 2025 Jun 17:104027. doi: 10.1016/j.mcn.2025.104027.

Li X, Shim S, Hardin KR, Vanaja KG, Song H, Levchenko A, Ming GL, and Zheng JQ (2022). Signal Amplification in Growth Cone Gradient Sensing by a Double Negative Feedback Loop among PTEN, PI(3,4,5)P3 and Actomyosin. Molecular and Cellular Neuroscience 123 (Dec).

Guirland C, Suzuki S, Kojima M, Lu B, and Zheng JQ (2004). Lipid Rafts Mediate Chemotropic Guidance of Nerve Growth Cones. Neuron 42(1):51-62.

Wen Z, Guirland C, Ming G-L, and Zheng JQ (2004). A CaMKII/Calcineurin Switch Controls the Direction of Ca2+-dependent Growth Cone Guidance. Neuron 43(6):835-846.

Zheng JQ (2000). Turning of Nerve Growth Cones Induced by Localized Increases in Intracellular Calcium Ions. Nature 403:89-93 (Jan. 6).

Hippocampal circuitry, Synapse, and Plasticity

Synapses represent the basic unit of neuronal communications and most of the excitatory synapses reside on dendritic spines, a type of dendritic protrusions that host neurotransmitter receptors and other postsynaptic specializations. Synapses are plastic and undergo short- and long-term modifications during developmental refinement of neuronal circuitry, as well as during learning and memory. Synaptic modifications involve both pre- and post-synaptic changes. Postsynaptically, modifications of the surface neurotransmitter receptors (numbers and properties) are believed to be a key event underlying the changes in synaptic strength. In addition, dendritic spines undergo rapid changes in shape and size in association with synaptic modifications. Our lab is interested in the cytoskeletal mechanisms that underlie the spine development during synaptogenesis and postsynaptic modifications during synaptic plasticity. In particular, we have been studying the role of microtubules and the actin dynamics in spine formation, dynamics, and synaptic receptor trafficking. Since many neurological disorders have been associated with alterations in synaptic connections, we hope that our studies will also shed light on brain development and functions under both physiological and pathological conditions.

Featured publications:

Myers KR, Fan Y, McConnell P, Cooper JA, Zheng JQ (2022) 'Actin capping protein regulates postsynaptic spine development through CPI-motif interactions.' Front Mol Neurosci, 15 (): 1020949. PMID: 36245917.

Omotade OF, Rui Y, Lei W, Yu K, Hartzell HC, Fowler VM, Zheng JQ (2018). Tropomodulin Isoform-Specific Regulation of Dendrite Development and Synapse Formation. J Neurosci. 2018 Nov 28;38(48):10271-10285.

Lei W, Myers KR, Rui Y, Hladyshau S, Tsygankov D, Zheng JQ (2017). Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity. J Cell Biol. 2017 Aug 7;216(8):2551-2564.

Fan Y, Tang X, Vitriol E, Chen G, and Zheng JQ (2011). Actin Capping Protein is Required for Dendritic Spine Development and Synapse Formation. Journal of Neuroscience 31(28):10228-10233.

Gu J, Lee CW, Fan Y, Komlos D, Tang X, Sun C, Yu K, Hartzell HC, Chen G, Bamburg JR, and Zheng JQ (2010). ADF/Cofilin-Mediated Actin Dynamics Regulate AMPA Receptor Trafficking during Synaptic Plasticity. Nature Neuroscience 13(10):1208-1215.

Neurodegeneration and Environmental Insults

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive loss of structure or function of neurons, leading to cognitive and motor impairments. The prevalence of these diseases increases with age, posing significant challenges to public health. While genetic factors contribute to the risk of developing neurodegenerative diseases, environmental factors, such as traumatic brain injury (TBI), have also been implicated in triggering or accelerating disease progression. We utilize Drosophila melanogaster as a model organism to investigate how environmental insults, particularly mild head trauma, influence the onset and progression of neurodegenerative diseases in aging populations. By combining advanced techniques such as AI-driven behavioral tracking and whole-brain imaging, we aim to elucidate the cellular and molecular mechanisms underlying age-related neurodegeneration and identify potential therapeutic targets.

Featured publications

Ye C, Ho R, Moberg KH, Zheng JQ (2024) 'Adverse impact of female reproductive signaling on age-dependent neurodegeneration after mild head trauma in Drosophila.' Elife, 13 (): PMID: 39213032

Ye C, Behnke JA, Hardin KR, Zheng JQ (2023) 'Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma.' Front Neurosci, 17 (): 1150694. PMID: 37077318

Behnke JA, Ye C, Setty A, Moberg KH, Zheng JQ (2021) 'Repetitive mild head trauma induces activity mediated lifelong brain deficits in a novel Drosophila model.' Sci Rep, 11 (1): 9738. PMID: 33958652.

Behnke JA, Ye C, Moberg KH, Zheng JQ (2021) 'A protocol to detect neurodegeneration in Drosophila melanogaster whole-brain mounts using advanced microscopy.' STAR Protoc, 2 (3): 100689. PMID: 34382016.