Article
Neurosciences
Priyadharshini Prabhakar, Rainer Pielot, Peter Landgraf, Josef Wissing, Anne Bayrhammer, Marco van Ham, Eckart D. Gundelfinger, Lothar Jaensch, Daniela C. Dieterich, Anke Mueller
Summary: Astrocytes display regional heterogeneity in morphology, function, and molecular composition, and play a role in supporting and modulating neuronal function and signaling. Using mass spectrometry and gene enrichment analysis, we discovered subtle differences in astrocytic proteomes among different brain regions, with the cerebellum showing a strong association with the calcium signaling pathway or bipolar disorder. Additionally, our toolbox proved to be applicable for studying astrocytic proteome differences in vivo.
Review
Biochemistry & Molecular Biology
Alexander K. Zinsmaier, Yan Dong, Yanhua H. Huang
Summary: Cocaine craving, seeking, and relapse are partially mediated by adaptive changes in the brain reward circuits induced by cocaine. The nucleus accumbens integrates emotional and motivational inputs and prioritizes them for the reward system. Medium spiny neurons in the NAc show complex adaptations following cocaine experience, influenced by various factors such as cocaine regimen, withdrawal time, cell type, location, and input/output projections.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemical Research Methods
Natalia Prudente de Mello, Caroline Fecher, Adrian Marti Pastor, Fabiana Perocchi, Thomas Misgeld
Summary: This protocol enables the ex vivo immunocapture of cell-type-specific mitochondria directly from their tissue context in heterogeneous tissues, such as the nervous system, using MitoTag reporter mice. The protocol allows for the selective isolation of functional mitochondria from medium-to-low-abundant cell types, revealing cell-type-specific mitochondrial diversity in molecular composition and function. The approach facilitates the identification of marker proteins to label cell-type-specific organelle populations and elucidates cell-type-enriched mitochondrial metabolic and signaling pathways.
Article
Cell Biology
Alexei M. Bygrave, Ayesha Sengupta, Ella P. Jackert, Mehroz Ahmed, Beloved Adenuga, Erik Nelson, Hana L. Goldschmidt, Richard C. Johnson, Haining Zhong, Felix L. Yeh, Morgan Sheng, Richard L. Huganir
Summary: Synapses in the brain display cell-type-specific differences, and Btbd11, an inhibitory interneuron-specific, synapse-enriched protein, plays a crucial role in glutamatergic synapse function. Btbd11 can undergo liquid-liquid phase separation and affects glutamatergic signaling, network activity, and behavior, highlighting its importance in circuit function and animal behavior.
Article
Cell Biology
Sheeja Navakkode, Jessica Ruth Gaunt, Maria Vazquez Pavon, Vibhavari Aysha Bansal, Riya Prasad Abraham, Yee Song Chong, Toh Hean Ch'ng, Sreedharan Sajikumar
Summary: Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease, but the cellular and molecular mechanisms remain unknown. Our studies on mouse models suggest that AD impacts hippocampal long-term plasticity in a sex-specific manner, with female mice showing faster decay in memory and synaptic plasticity, accompanied by neuroinflammatory markers upregulation. This disparity may contribute to the faster progression of AD in females.
Article
Multidisciplinary Sciences
Audrey Bonnan, Matthew M. J. Rowan, Christopher A. Baker, M. McLean Bolton, Jason M. Christie
Summary: The authors found that optogenetic activation of PCs generates dendritic Ca2+ signals that induce plasticity in vitro and instruct learned changes to coincident eye movements in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Beatrice Milon, Eldad D. Shulman, Kathy S. So, Christopher R. Cederroth, Erika L. Lipford, Michal Sperber, Jonathan B. Sellon, Heela Sarlus, Gabriela Pregernig, Benjamin Shuster, Yang Song, Sunayana Mitra, Joshua Orvis, Zachary Margulies, Yoko Ogawa, Christopher Shults, Didier A. Depireux, Adam T. Palermo, Barbara Canlon, Joe Burns, Ran Elkon, Ronna Hertzano
Summary: NIHL is caused by a complex interplay of damage to sensory cells, dysfunction of the lateral wall, axonal retraction, and immune response activation in the inner ear. While immune-related genes are induced across all cell-types, cell-type-specific transcriptomic changes dominate the response, with the ATF3/ATF4 stress-response pathway being robustly induced in noise-resilient neurons.
Article
Cell Biology
Quanxin Wang, Yun Wang, Hsien-Chi Kuo, Peng Xie, Xiuli Kuang, Karla E. Hirokawa, Maitham Naeemi, Shenqin Yao, Matt Mallory, Ben Ouellette, Phil Lesnar, Yaoyao Li, Min Ye, Chao Chen, Wei Xiong, Leila Ahmadinia, Laila El-Hifnawi, Ali Cetin, Staci A. Sorensen, Julie A. Harris, Hongkui Zeng, Christof Koch
Summary: Using multimodal reference datasets, the study confirmed the delineation of the mouse claustrum (CLA) as a single group of neurons embedded in the agranular insular cortex. Through quantitative investigation, the study revealed the brain-wide inputs and outputs of CLA and identified the cell-type-specific connections. The study also found that the prefrontal module has more cell types projecting to the CLA and identified nine morphological types of CLA principal neurons.
Article
Computer Science, Artificial Intelligence
Ilenna Simone Jones, Konrad Paul Kording
Summary: The study used a simple model to investigate how the architecture of dendrites affects neural computation, finding that model performance is influenced by binary branching and repetition of synaptic inputs. These findings contribute to a better understanding of how different dendritic properties impact neural computation.
NEURAL COMPUTATION
(2021)
Article
Biochemistry & Molecular Biology
Xue Li, Lu Zhang, Suyang Wang, Xiangqin Liu, Ying Lin
Summary: A novel site-specific internal protein labeling method using two atypical split inteins was demonstrated, allowing for the incorporation of a fluorescent probe into recombinant proteins. The number of native extein amino acids was shown to affect trans-splicing activity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Maria Kukley
Summary: This review discusses recent experimental findings on the functional role of AMPA receptors (AMPARs) in oligodendrocyte lineage cells in vivo, in mice and in zebrafish. The studies showed that oligodendroglial AMPARs may modulate proliferation, differentiation, migration, and survival of oligodendroglial cells. Targeting AMPAR subunit composition could be an important strategy for disease treatment. However, additional research is needed to fully understand the role of AMPARs in vivo, including considering the temporal and spatial aspects of AMPAR-mediated signaling in the oligodendrocyte lineage cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Takahisa Maki, Genevieve Thon, Hiroshi Iwasaki
Summary: A haploid of the fission yeast Schizosaccharomyces pombe expresses either the P or M mating-type through gene conversion, which is determined by the active mat1 cassette. The Swi2-Swi5 complex plays a crucial role in this process by selecting a preferred donor in a cell-type specific manner. Two important motifs in Swi2, a Swi6-binding site and two DNA-binding AT-hooks, have been identified and shown to be essential for its localization to the recombination enhancers in order to promote gene conversion.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Shalva Gurgenidze, Peter Baeuerle, Dietmar Schmitz, Imre Vida, Tengis Gloveli, Tamar Dugladze
Summary: A subset of parvalbumin-positive (PV+) interneurons (INs)-stuttering cells (STUT) with distinct morphological, electrophysiological, and synaptic properties in the medial entorhinal cortex (mEC) are described for the first time. These STUT cells have the ability to modulate gamma activity in the pyramidal cell population of the mEC. Activation of the mu-opioid receptors decreases the GABA release from the PV+ INs onto the STUT, resulting in an increase in network gamma power.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Allison L. Ludwig, Steven J. Mayerl, Yu Gao, Mark Banghart, Cole Bacig, Maria A. Fernandez Zepeda, Xinyu Zhao, David M. Gamm
Summary: This study demonstrates the ability of human pluripotent stem cell-derived retinal organoids to establish new synaptic connections after dissociation, enhancing their potential for use in cell replacement strategies. A high-throughput approach for labeling and quantifying traced retinal cell types was developed, with photoreceptors and retinal ganglion cells being the major contributing populations. This system provides a platform for assessing and enhancing synaptogenesis in cultured retinal neurons.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Psychiatry
Mouly F. Rahman, Patrick O. McGowan
Summary: Early life stress (ELS) leads to long-term phenotypic adaptations, increasing vulnerability to various neuropsychiatric disorders. Epigenetic modifications may serve as a link between environmental stressors, gene expression changes, and phenotypes. While studies have revealed epigenetic changes resulting from ELS, most of them have focused on heterogeneous brain tissue and neglected cell-type-specific modifications associated with ELS. Future research employing cell-type-specific methods can provide important mechanistic insights into the role of epigenetic variation in the effects of ELS on brain function.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Neurosciences
Orkun Akin, Bryce T. Bajar, Mehmet F. Keles, Mark A. Frye, S. Lawrence Zipursky
Review
Biochemistry & Molecular Biology
Joshua R. Sanes, S. Lawrence Zipursky
Letter
Biotechnology & Applied Microbiology
Alexandra M. Amen, Alexandra M. Amen, Kerrie W. Barry, John M. Boyle, Cara E. Brook, Seunga Choo, L. T. Cornmesser, David J. Dilworth, Jennifer A. Doudna, Alexander J. Ehrenberg, Indro Fedrigo, Skyler E. Friedline, Thomas G. W. Graham, Ralph Green, Jennifer R. Hamilton, Ariana Hirsh, Megan L. Hochstrasser, Dirk Hockemeyer, Netravathi Krishnappa, Azra Lari, Hanqin Li, Enrique Lin-Shiao, Tianlin Lu, Elijah F. Lyons, Kevin G. Mark, Lisa Argento Martell, A. Raquel O. Martins, Shana L. McDevitt, Patrick S. Mitchell, Erica A. Moehle, Christine Naca, Divya Nandakumar, Elizabeth O'Brien, Derek J. Pappas, Kathleen Pestal, Diana L. Quach, Benjamin E. Rubin, Rohan Sachdeva, Elizabeth C. Stahl, Abdullah Muhammad Syed, I-Li Tan, Amy L. Tollner, Connor A. Tsuchida, C. Kimberly Tsui, Timothy K. Turkalo, Fyodor D. Urnov, M. Bryan Warf, Oscar N. Whitney, Lea B. Witkowsky
NATURE BIOTECHNOLOGY
(2020)
Article
Neurosciences
Matthew B. Veldman, Chang Sin Park, Charles M. Eyermann, Jason Y. Zhang, Elizabeth Zuniga-Sanchez, Arlene A. Hirano, Tanya L. Daigle, Nicholas N. Foster, Muye Zhu, Peter Langfelder, Ivan A. Lopez, Nicholas C. Brecha, S. Lawrence Zipursky, Hongkui Zeng, Hong-Wei Dong, X. William Yang
Review
Multidisciplinary Sciences
Melissa G. Metcalf, Ryo Higuchi-Sanabria, Gilberto Garcia, C. Kimberly Tsui, Andrew Dillin
Article
Neurosciences
Liming Tan, Elaine Tring, Dario L. Ringach, S. Lawrence Zipursky, Joshua T. Trachtenberg
Article
Cell Biology
Orkun Akin, S. Lawrence Zipursky
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2020)
Article
Neurosciences
Yerbol Z. Kurmangaliyev, Juyoun Yoo, Javier Valdes-Aleman, Piero Sanfilippo, S. Lawrence Zipursky
Article
Multidisciplinary Sciences
Julea Vlassakis, Louise L. Hansen, Ryo Higuchi-Sanabria, Yun Zhou, C. Kimberly Tsui, Andrew Dillin, Haiyan Huang, Amy E. Herr
Summary: This research introduces a novel method to simultaneously detect protein complexes in stressed cell populations, revealing potential cellular responses to specific treatments. The study also highlights the impact of non-chemical stress on cellular heterogeneity of F-actin. The assay developed in this work overcomes selectivity limitations to biochemically quantify single-cell protein complexes perturbed with diverse stimuli.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Saumya Jain, Ying Lin, Yerbol Z. Kurmangaliyev, Javier Valdes-Aleman, Samuel A. LoCascio, Parmis Mirshahidi, Brianna Parrington, S. Lawrence Zipursky
Summary: Integration of a global temporal transcriptional module with cell-type-specific transcription factors influences neuronal wiring and synaptic connectivity in the fly visual system. The steroid hormone ecdysone induces a cascade of transcription factors in all fly visual system neurons, regulating the expression of a common set of targets required for synaptic maturation and cell-type-specific targets enriched for cell-surface proteins regulating wiring specificity. Disruption of the ecdysone pathway leads to specific defects in dendritic and axonal processes and synaptic connectivity, with sequential expression of transcription factors correlating with wiring steps. Shared targets of a cell-type-specific transcription factor and the ecdysone pathway regulate wiring specificity. Neurons integrate temporal transcriptional regulation and cell-type-specific regulation to generate cell-type-specific patterns of cell recognition molecules influencing neuronal wiring.
Article
Multidisciplinary Sciences
Bryce T. Bajar, Nguyen T. Phi, Jesse Isaacman-Beck, Jun Reichl, Harpreet Randhawa, Orkun Akin
Summary: Research has found that patterned neural activity during the development of the fruit fly's central nervous system is coordinated by a small population of neurons expressing the Trp gamma gene. This activity is essential for the formation of synaptic connections and the assembly of the brain. The study establishes the fruit fly's brain as a useful model system for investigating how neural activity contributes to the formation of synapses and circuits.
Article
Multidisciplinary Sciences
Erica A. Moehle, Ryo Higuchi-Sanabria, C. Kimberly Tsui, Stefan Homentcovschi, Kevin M. Tharp, Hanlin Zhang, Hannah Chi, Larry Joe, Mattias de Los Rios Rogers, Arushi Sahay, Naame Kelet, Camila Benitez, Raz Bar-Ziv, Gilberto Garcia, Koning Shen, Phillip A. Frankino, Robert T. Schinzel, Ophir Shalem, Andrew Dillin
Summary: Mitochondrial dysfunction is linked to aging and age-related diseases, prompting the need for quality control mechanisms like the unfolded protein response of the mitochondria (UPRMT). Cross-species comparisons can uncover new components of the mammalian UPRMT, as shown in this study which identified the role of EPS-8 in mitochondrial homeostasis and UPRMT regulation. The study also highlights the value of using genetic screens across different species to investigate cellular pathways.
Article
Developmental Biology
Bryce T. Bajar, Nguyen T. Phi, Harpreet Randhawa, Orkun Akin
Summary: This study demonstrates the necessity of astrocytes for developmental activity during synaptogenesis in Drosophila. The glia of the central nervous system participate in developmental activity with type-specific patterns of intracellular calcium dynamics. Genetic ablation of astrocytes leads to severe attenuation of neuronal activity, and inhibition of neuronal activity results in the loss of astrocyte calcium dynamics. Astrocytic calcium cycles can influence neuronal activity but are not necessary per se.
DEVELOPMENTAL NEUROBIOLOGY
(2022)