Article
Geriatrics & Gerontology
Xi Chen, Zhaofei Yang, Yaping Shao, Kunhyok Kim, Yuanyuan Wang, Ying Wang, Haifeng Wu, Xiaolan Xu, Weidong Le
Summary: The PD mouse model exhibited early changes in neurotransmitters, morphology, and DNA methylation within MSNs, which in turn may contribute to alterations in metabolism, morphology, and epigenetics within the striatum in the later stages of the disease.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Cell Biology
Viktor Yarotskyy, Arianna R. S. Lark, Sara R. Nass, Yun K. Hahn, Michael G. Marone, A. Rory McQuiston, Pamela E. Knapp, Kurt F. Hauser
Summary: This study reveals the presence of ClC-1 chloride channels in striatal neurons, mainly localized to the somata of the neurons. These channels modulate neuronal excitability.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaohui Bai, Kun Zhang, Chaopeng Ou, Yanyu Mu, Dongmei Chi, Jianxing Zhang, Jingxiu Huang, Xile Li, Yingjun Zhang, Wan Huang, Handong Ouyang
Summary: This study found that the expression of AKAP150 in the NAc is upregulated during morphine withdrawal, and inhibiting AKAP150 has a positive effect on alleviating withdrawal symptoms and improving test performance. AKAP150 in NAc D1R-MSNs is related to the performance of morphine withdrawal tests, while AKAP150 in NAc D2R-MSNs is relevant to the severity of physical responses.
Article
Cell Biology
Shannon L. Gourley, Kolluru D. Srikanth, Ellen P. Woon, Hava Gil-Henn
Summary: The study found that Pyk2 stabilizes the structure of the striatal medium spiny neurons, likely providing substrates for inputs, and supports the capacity of mice to arbitrate between novel and familiar behaviors through interactions with the medial prefrontal cortex. Experiments demonstrated that Pyk2 loss caused dendrite arbor and spine loss, while overexpression of Pyk2 or the closely related focal adhesion kinase (FAK) enhanced the ability of mice to arbitrate between rewarded and non-rewarded behaviors. Additionally, combinatorial viral vector strategies suggested that flexible, Pyk2-dependent action involves inputs from the medial prefrontal cortex (mPFC), not the ventrolateral orbitofrontal cortex (OFC).
Article
Cell Biology
Thomas Andreska, Patrick Luningschror, Daniel Wolf, Rhonda L. McFleder, Maurilyn Ayon-Olivas, Marta Rattka, Christine Drechsler, Veronika Perschin, Robert Blum, Sarah Aufmkolk, Noelia Granado, Rosario Moratalla, Markus Sauer, Camelia Monoranu, Jens Volkmann, Chi Wang Ip, Christian Stigloher, Michael Sendtner
Summary: Parkinson's disease (PD) is characterized by impaired motor control. Cortico-striatal synapses, along with brain-derived neurotrophic factor (BDNF) and TrkB, play crucial roles in motor learning. Dopamine depletion in PD reduces the responsiveness of striatal medium spiny projection neurons (SPNs) to BDNF, leading to impaired TrkB processing and disturbed motor function. Sortilin related VPS10 domain containing receptor 2 (SORCS-2) may protect intracellular TrkB clusters from lysosomal degradation.
Article
Biochemistry & Molecular Biology
Anna Kutschenko, Selma Staege, Karen Grutz, Hannes Glab, Norman Kalmbach, Thomas Gschwendtberger, Lisa M. Henkel, Johanne Heine, Anne Grunewald, Andreas Hermann, Philip Seibler, Florian Wegner
Summary: Myoclonus-dystonia (DYT-SGCE), a rare neurological disorder caused by mutations in the SGCE gene, is characterized by abnormal Ca2+ signaling, synaptic density, and electrical properties in patient-derived neurons. This study provides insights into the pathophysiology of the disease and potential novel therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Guendalina Bergonzoni, Jessica Doring, Marta Biagioli
Summary: Huntington's disease is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the HTT gene. Despite the ubiquity of the HTT gene, striatal Medium-sized Spiny Neurons are particularly vulnerable to the HD mutation, with D1R and D2R displaying different susceptibility. Understanding cell type-specific gene expression dysregulation in the striatum may offer new paths for therapeutic intervention in HD patients.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Zheng-Dong Zhao, Xiao Han, Renchao Chen, Yiqiong Liu, Aritra Bhattacherjee, Wenqiang Chen, Yi Zhang
Summary: The striatum plays a critical role in regulating addiction-related behaviors. A subtype of D1 MSNs, Tac2+, demonstrates an unconventional and subtype/projection-specific negative regulatory function in drug addiction.
Article
Multidisciplinary Sciences
Kim Le Cann, Alec Foerster, Corinna Roesseler, Andelain Erickson, Petra Hautvast, Sebastian Giesselmann, Daniel Pensold, Ingo Kurth, Markus Rothermel, Virginia B. Mattis, Geraldine Zimmer-Bensch, Stephan von Hoersten, Bernd Denecke, Tim Clarner, Jannis Meents, Angelika Lampert
Summary: Huntington's disease (HD) is a neurodegenerative disorder caused by a genetic mutation, affecting specific neuronal populations in the brain. Differentiating hiPS cells into striatal neurons to model HD faces challenges in replicating previous protocols due to heterogeneity in neuronal populations and variability in Nav channels. The study highlights difficulties in generating accurate hiPS cell-derived MSNs for studying HD in vitro.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Lior Matityahu, Jeffrey M. Malgady, Meital Schirelman, Yvonne Johansson, Jennifer A. Wilking, Gilad Silberberg, Joshua A. Goldberg, Joshua L. Plotkin, Jun Ding
Summary: Striatal spiny projection neurons (SPNs) shape basal ganglia output by transforming corticostriatal inputs into inhibitory signals. Striatal GABAergic interneurons (GINs) provide rapid corticostriatal feedforward inhibition to SPNs, while cholinergic interneurons (CINs) inhibit SPNs by activating nicotinic acetylcholine receptors (nAChRs) on GINs. The disynaptic inhibitory pathway mediated by nAChRs is slower than direct GIN-mediated feedforward inhibition, and the role of nAChRs in striatal synaptic integration is unclear.
Article
Cell Biology
Lisa M. Henkel, Svenja Kankowski, Thiemo M. Moellenkamp, Nadine J. Smandzich, Sigrid Schwarz, Alessio Di Fonzo, Gudrun Goehring, Guenter Hoeglinger, Florian Wegner
Summary: In this study, induced pluripotent stem cells (iPSCs) were generated and differentiated into medium spiny neurons (MSNs) in the striatum from patients with probable MSA-P and healthy controls. The MSNs derived from MSA-P patients showed significantly elevated release and neuronal distribution of alpha-synuclein, as well as hypoexcitability compared to healthy controls. These findings suggest that hypoexcitable neurons in the striatum of MSA-P patients contribute to the pathological burden of alpha-synuclein and facilitate disease progression.
Article
Cell Biology
Selma Staege, Anna Kutschenko, Hauke Baumann, Hannes Glass, Lisa Henkel, Thomas Gschwendtberger, Norman Kalmbach, Martin Klietz, Andreas Hermann, Katja Lohmann, Philip Seibler, Florian Wegner
Summary: DYT-THAP1 dystonia is an adolescent-onset disorder characterized by involuntary muscle contractions, caused by mutations in the THAP1 gene. Decreased GABAergic synaptic transmission, neuronal disinhibition, and hyperexcitability were observed in affected individuals. These findings provide pathophysiological insights and may contribute to the development of novel treatment strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Manli Zhong, Yuhan Wang, Geng Lin, Francesca-Fang Liao, Fu-Ming Zhou
Summary: This study found that in mice, the medium spiny neurons responsible for motor control and cognition in the striatum are not affected by dopamine loss, contrary to previous theories.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Yuqi Ren, Yang Liu, Minmin Luo
Summary: The striatum is involved in various behaviors and its D1-type projection neurons are directly electrically coupled to cholinergic interneurons (ChIs), in addition to chemical transmission. Activation of D1 neurons promotes basal activity of ChIs through gap junctions, contributing to the maintenance of ChIs' tonically active firing patterns.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Xuan Wang, Zhenfeng Shu, Quansheng He, Xiaowen Zhang, Luozheng Li, Xiaoxue Zhang, Liang Li, Yujie Xiao, Bo Peng, Feifan Guo, Da-Hui Wang, Yousheng Shu
Summary: This study found that parvalbumin neurons in the striatum have functional autapses, while principal spiny projection neurons do not. The autaptic responses in parvalbumin neurons are mediated by GABA(A) receptors and regulate their spiking activity. These autapses may play important roles in striatal functions.
NEUROSCIENCE BULLETIN
(2023)
Article
Neurosciences
Kim T. Blackwell, Armando G. Salinas, Parul Tewatia, Brad English, Jeanette Hellgren Kotaleski, David M. Lovinger
EUROPEAN JOURNAL OF NEUROSCIENCE
(2019)
Article
Multidisciplinary Sciences
J. J. Johannes Hjorth, Alexander Kozlov, Ilaria Carannante, Johanna Frost Nylen, Robert Lindroos, Yvonne Johansson, Anna Tokarska, Matthijs C. Dorst, Shreyas M. Suryanarayana, Gilad Silberberg, Jeanette Hellgren Kotaleski, Sten Grillner
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Neurosciences
Johanna Frost Nylen, Ilaria Carannante, Sten Grillner, Jeanette Hellgren Kotaleski
Summary: The striatum serves as the main input stage of the basal ganglia, with cholinergic (ChIN) and low-threshold spiking interneurons (LTS) forming a subnetwork involved in salience detection and goal-directed learning. Thalamic input preferentially excites ChINs, while input from the motor cortex favors LTS.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Robert Lindroos, Jeanette Hellgren Kotaleski
Summary: The study investigated the impact of dopamine and acetylcholine on neurons, revealing that they can affect the excitability of striatal projection neurons. When both substances act simultaneously, they can result in complex spike patterns.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Computer Science, Interdisciplinary Applications
Mathew Birdsall Abrams, Jan G. Bjaalie, Samir Das, Gary F. Egan, Satrajit S. Ghosh, Wojtek J. Goscinski, Jeffrey S. Grethe, Jeanette Hellgren Kotaleski, Eric Tatt Wei Ho, David N. Kennedy, Linda J. Lanyon, Trygve B. Leergaard, Helen S. Mayberg, Luciano Milanesi, Roman Moucek, J. B. Poline, Prasun K. Roy, Stephen C. Strother, Tong Boon Tang, Paul Tiesinga, Thomas Wachtler, Daniel K. Wojcik, Maryann E. Martone
Summary: There is a great need for coordination around standards and best practices in neuroscience to address challenges in data science. Developing community standards and gaining their adoption is difficult, as the current landscape is characterized by a lack of robust, validated standards and a plethora of underdeveloped and underutilized standards and best practices. An independent organization, the International Neuroinformatics Coordinating Facility (INCF), is dedicated to promoting data sharing in neuroscience and has implemented procedures for evaluating and endorsing community standards and best practices.
Correction
Computer Science, Interdisciplinary Applications
Mathew Birdsall Abrams, Jan G. Bjaalie, Samir Das, Gary F. Egan, Satrajit S. Ghosh, Wojtek J. Goscinski, Jeffrey S. Grethe, Jeanette Hellgren Kotaleski, Eric Tatt Wei Ho, David N. Kennedy, Linda J. Lanyon, Trygve B. Leergaard, Helen S. Mayberg, Luciano Milanesi, Roman Moucek, J. B. Poline, Prasun K. Roy, Stephen C. Strother, Tong Boon Tang, Paul Tiesinga, Thomas Wachtler, Daniel K. Wojcik, Maryann E. Martone
Article
Computer Science, Interdisciplinary Applications
J. J. Johannes Hjorth, Jeanette Hellgren Kotaleski, Alexander Kozlov
Summary: Simulation of large-scale networks of neurons is crucial for understanding and interpreting experimental data from healthy and diseased brains. By predicting the computational and dynamical properties of local microcircuits using simulation software and quantitative data of neuronal types, simulations can be compared with experiments and used to bridge different scales. An open source pipeline is described for predicting microcircuit connectivity, setting up simulations, and curating neuron morphology data, with the example of a cellular level model of mouse dorsal striatum.
Article
Computer Science, Interdisciplinary Applications
Joao P. G. Santos, Kadri Pajo, Daniel Trpevski, Andrey Stepaniuk, Olivia Eriksson, Anu G. Nair, Daniel Keller, Jeanette Hellgren Kotaleski, Andrei Kramer
Summary: The article describes a workflow for building and analyzing biochemical pathway models, utilizing existing tools and software to address challenges related to conversion between different model formats and interoperability.
Article
Neurosciences
Johanna Frost Nylen, Jarl Jacob Johannes Hjorth, Sten Grillner, Jeanette Hellgren Kotaleski
Summary: Neuromodulation plays a critical role in the nervous system, supporting circuit function and dynamics in large-scale networks. Software platforms like Snudda and Neuromodcell are developed for simulating and optimizing neuromodulation by modulating ion channels and ionotropic receptors in detailed neuron models.
FRONTIERS IN NEURAL CIRCUITS
(2021)
Article
Biology
Timothy W. Church, Parul Tewatia, Saad Hannan, Joao Antunes, Olivia Eriksson, Trevor G. Smart, Jeanette Hellgren Kotaleski, Matthew G. Gold
Summary: The study found that AKAP79 enhances calcineurin activity, which leads to the suppression of PKA without altering cAMP levels. This non-canonical mode of PKA regulation may play a role in many other cellular processes.
Article
Neurosciences
Kingshuk Chakravarty, Sangheeta Roy, Aniruddha Sinha, Atsushi Nambu, Satomi Chiken, Jeanette Hellgren Kotaleski, Arvind Kumar
Summary: The basal ganglia is crucial for motor and cognitive functions. Persistent low-dopamine induces changes in steady-state population activity and transient response of the basal ganglia. This study used numerical simulations to identify key factors shaping the transient response in low-dopamine state.
Article
Chemistry, Multidisciplinary
Siri C. van Keulen, Juliette Martin, Francesco Colizzi, Elisa Frezza, Daniel Trpevski, Nuria Cirauqui Diaz, Pietro Vidossich, Ursula Rothlisberger, Jeanette Hellgren Kotaleski, Rebecca C. Wade, Paolo Carloni
Summary: This study used simulation tools to uncover the molecular and subcellular mechanisms of AC function, with a focus on the AC5 isoform. The research revealed an inactive state of the enzyme in the presence of an inhibitory G alpha subunit, regardless of the presence of a stimulatory G alpha. The binding of G alpha subunits reshaped the free-energy landscape of the AC5 enzyme.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Review
Biology
Olivia Eriksson, Upinder Singh Bhalla, Kim T. Blackwell, Sharon M. Crook, Daniel Keller, Andrei Kramer, Marja-Leena Linne, Ausra Saudargiene, Rebecca C. Wade, Jeanette Hellgren Kotaleski
Summary: Modeling in neuroscience involves hypothesis-driven and data-driven approaches, with models constructed at different biological scales and levels of abstraction. However, a lack of interoperability, transparency, and reusability of models and workflows hinders the integration of models representing different scales and built using different methods. Applying the FAIR principles to models and workflows can facilitate integration and enhance understanding of the brain.
Article
Multidisciplinary Sciences
Yichen Zhang, Gan He, Lei Ma, Xiaofei Liu, J. J. Johannes Hjorth, Alexander Kozlov, Yutao He, Shenjian Zhang, Jeanette Hellgren Kotaleski, Yonghong Tian, Sten Grillner, Kai Du, Tiejun Huang
Summary: Biophysically detailed multi-compartment models are powerful tools for exploring brain computational principles and generating AI algorithms. The high computational cost limits their applications. Researchers propose a novel dendritic hierarchical scheduling method that significantly accelerates simulations using GPU computing engine, and demonstrate its applications in neuroscience tasks.
NATURE COMMUNICATIONS
(2023)
Article
Physiology
Sten Grillner, Brita Robertson, Jeanette Hellgren Kotaleski
COMPREHENSIVE PHYSIOLOGY
(2020)