Article
Neurosciences
D. Leonardo Garcia-Ramirez, Ngoc T. Ha, Steve Bibu, Nicholas J. Stachowski, Kimberly J. Dougherty
Summary: The impact of spinal cord injury on Shox2 interneurons mainly manifests as changes in sensory afferent input pathways and modulation of Shox2 interneurons by 5-HT, enhancing excitatory responses.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Lyandysha Zholudeva, Victoria E. Abraira, Kajana Satkunendrarajah, Todd C. McDevitt, Martyn D. Goulding, David S. K. Magnuson, Michael A. Lane
Summary: Spinal interneurons play a crucial role in the intact CNS, contributing to the control and modulation of motor, sensory, and autonomic functions, with potential changes following traumatic spinal cord injury. Treatments optimizing the contribution of interneurons to functional improvement are also discussed.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Eric Brown, Ayma F. Malik, Elizabeth R. Moese, Abigail F. McElroy, Angelo C. Lepore
Summary: Neuropathic pain (NP) is a common and debilitating comorbidity of spinal cord injury (SCI). This study investigates the neural activity changes in the pain circuitry following cervical spinal cord injury. The findings reveal complex changes in neuronal activation, with increased activation in some neurons and decreased activation in inhibitory neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Nicholas J. Stachowski, Kimberly J. Dougherty
Summary: The spinal cord is crucial in mediating sensory responses and coordinating movement by activating complex spinal microcircuits that filter external stimuli and determine which signals are transmitted to higher order structures in the CNS. Recent studies have identified distinct populations of inhibitory interneurons in the dorsal and ventral spinal cord, highlighting the importance of inhibitory control in sensorimotor pathways at the spinal level.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Antonella Comitato, Enza Lacivita, Marcello Leopoldo, Rita Bardoni
Summary: The 5-HT7 receptors play an important role in synaptic modulation, particularly in synaptic inhibition, in the dorsal horn of the spinal cord. The stronger impact on synaptic inhibition suggests that these receptors may have an anti-nociceptive role in the spinal cord of naive animals.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biology
Lisa A. E. Catsburg, Manon Westra, Annemarie M. L. van Schaik, Harold D. MacGillavry
Summary: This study reveals the dynamic organization of the clathrin-coated structure at postsynaptic sites and its role in synaptic plasticity. The endocytic zone (EZ) acts as a stable and highly organized molecular platform, where different components are recruited and positioned to regulate the endocytosis of synaptic receptors.
Article
Neurosciences
Ziyun Huang, Liping Sun, Xuefeng Zheng, Ye Zhang, Yaxi Zhu, Tao Chen, Zhi Chen, Linju Ja, Lisi OuYang, Yaofeng Zhu, Si Chen, Wanlong Lei
Summary: In this study, nerve tracing, immunohistochemistry, and immunoelectron microscopy were used to explore and confirm the synaptic connections between the cerebral cortex and motor neurons in the spinal cord. The findings revealed that the cortical fibers primarily had a contralateral distribution in the spinal cord, with a denser presence in the ventral horn. Electron microscopy confirmed that these fibers formed asymmetric synapses with spinal neurons. Immunofluorescence labeling showed clear apposition points between the cortical fibers, synaptophysin, and spinal interneurons.
FRONTIERS IN NEURAL CIRCUITS
(2023)
Article
Neurosciences
Volodymyr Krotov, Kirill Agashkov, Sergii Romanenko, Oleh Halaidych, Yaroslav Andrianov, Boris V. V. Safronov, Pavel Belan, Nana Voitenko
Summary: Although our understanding of how afferent-driven presynaptic inhibition shapes peripheral input to nociceptive neurons is limited, this study examined this effect on primary afferent input to spinal neurons in two nociceptive-processing regions. The results showed that attenuation of presynaptic inhibition resulted in the appearance of new mono- and polysynaptic excitatory postsynaptic current components. These mechanisms are important for shaping primary afferent input to neurons in the spinal nociceptive-processing network.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Rong Hu, Kelin He, Bowen Chen, Yi Chen, Jieqi Zhang, Xingying Wu, Mengting Shi, Lei Wu, Ruijie Ma
Summary: Neurocan in the perineuronal net (PNN) can regulate the activity of PV-IN, and electroacupuncture (EA) can promote functional recovery in mice with spinal cord injury (SCI) by upregulating neurocan expression in the PNN.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Kensho Kanehisa, Keisuke Koga, Sho Maejima, Yuto Shiraishi, Konatsu Asai, Miho Shiratori-Hayashi, Mei-Fang Xiao, Hirotaka Sakamoto, Paul F. Worley, Makoto Tsuda
Summary: This study reveals that neuronal pentraxin 2 (NPTX2) upregulation in primary sensory neurons facilitates excitatory synaptic inputs onto gastrin-releasing peptide receptors (GRPR) expressing spinal neurons in chronic itch models.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
W. L. Tai, L. Sun, H. Li, P. Gu, E. A. Joosten, C. W. Cheung
Summary: The joint treatment of environmental enrichment (EE) and clinical analgesic ketamine has been shown to provide greater relief of spinal cord injury-induced neuropathic pain and motor dysfunction by reducing spinal glutamatergic activation.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Bruno Benedetti, Annika Weidenhammer, Maximilian Reisinger, Sebastien Couillard-Despres
Summary: Evidence suggests that cortical disinhibition can be either beneficial or detrimental in a context-dependent manner. Careful examination of clinical data and research using SCI animal models can help to better understand this mechanism and improve treatment outcomes through targeted pharmacological and rehabilitative interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Steve J. Sullivan, Andrei D. Sdrulla
Summary: Excitatory and inhibitory neurons in the superficial dorsal horn (SDH) of the spinal cord diverge considerably in their somatosensory responses and plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Yuying Huang, Hong Chen, Daozhong Jin, Shao-Rui Chen, Hui -Lin Pan
Summary: The spinal dorsal horn contains excitatory neurons expressing vesicular glutamate transporter-2 (VGluT2) and inhibitory neurons expressing vesicular GABA transporter (VGAT), which have different roles in nociceptive transmission. The study shows that presynaptic NMDARs amplify primary afferent input in neuropathic pain, while postsynaptic NMDARs play a dominant role in chronic pain caused by traumatic nerve injury. This reveals the divergent synaptic connectivity and functional significance of presynaptic and postsynaptic NMDARs in regulating cell type-specific nociceptive input in neuropathic pain with different etiologies.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Jia Xu, Liang-Jiang Huang, Zhengyu Fang, Hong-Mei Luo, Yun-Qiang Chen, Ya-Jie Li, Chen-Zi Gong, Hong Chen
Summary: In this study, a reproducible protocol was developed to differentiate human pluripotent stem cells into enriched spinal inhibitory GABAergic interneurons (INs). This protocol has the potential to advance the study of human spinal IN development and facilitate regenerative therapies for spinal cord injuries and diseases.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Hideki Miwa, Ken Kobayashi, Shinobu Hirai, Mitsuhiko Yamada, Masahiko Watanabe, Haruo Okado, Yuchio Yanagawa
Summary: The study reveals the critical role of GABA in establishing connections between basket cells and Purkinje cells in the cerebellum, and its association with motor coordination in mice.
Article
Cell Biology
Anussara Kamnate, Juthathip Sirisin, Masahiko Watanabe, Hisatake Kondo, Wiphawi Hipkaeo, Surang Chomphoo
Summary: The study found that cannabinoid receptor type 1 (CB1) is localized on mitochondrial membranes in ovarian interstitial gland cells of adult mice, potentially modulating the synthetic process of progesterone through CB1.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2022)
Article
Neurosciences
Ken Matsuura, Shizuka Kobayashi, Kohtarou Konno, Miwako Yamasaki, Takahiro Horiuchi, Takao Senda, Tomoatsu Hayashi, Kiyotoshi Satoh, Fumiko Arima-Yoshida, Kei Iwasaki, Lumi Negishi, Naomi Yasui-Shimizu, Kazuyoshi Kohu, Shigenori Kawahara, Yutaka Kirino, Tsutomu Nakamura, Masahiko Watanabe, Tadashi Yamamoto, Toshiya Manabe, Tetsu Akiyama
Summary: The study reveals that SIPA1L1 is mainly localized to submembranous regions in neurons, and its deficiency may be associated with neuropsychiatric disorders related to dysregulated GPCR signaling.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa, Kenji Sakimura, Susumu Tomita, Masahiko Watanabe, Pablo E. Castillo
Summary: This study provides the first direct evidence of functional extrasynaptic kainate receptors (KARs) on mossy cells (MCs) in the hippocampus. These KARs are mainly located extrasynaptically and play a critical role in the activity of MCs. Increases in ambient glutamate can activate the KARs on MCs.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell & Tissue Engineering
Yuka Kasahara, Daiki Masukawa, Kenta Kobayashi, Miwako Yamasaki, Masahiko Watanabe, Yoshio Goshima
Summary: Neurogenesis in the hippocampus is regulated by L-DOPA and its receptor GPR143 independently of dopamine. Low concentrations of L-DOPA promote neurogenesis, and its effect is abolished in GPR143 gene-deficient mice. Decreased neurogenesis and exacerbated depression-like behavior are observed in adult GPR143 gene-deficient mice, but can be attenuated by replenishment of GPR143 in the hippocampus.
Article
Anesthesiology
Erika Polgar, Allen C. Dickie, Maria Gutierrez-Mecinas, Andrew M. Bell, Kieran A. Boyle, Raphaelle Quillet, Elisha Ab Rashid, Ross A. Clark, Morgan T. German, Masahiko Watanabe, John S. Riddell, Andrew J. Todd
Summary: Neurons in the superficial dorsal horn expressing GRPR are implicated in spinal itch pathways, but they also show characteristics of nociceptive interneurons. Using a GRPR(CreERT2) mouse line, this study identifies and targets cells with Grpr mRNA, revealing that GRPR cells are glutamatergic, concentrated in specific areas of the dorsal horn, and account for about 15% of excitatory neurons. These cells largely differ from other excitatory interneuron populations and receive monosynaptic input from Trpv1-expressing nociceptive afferents, responding to both pain and pruritic stimuli.
Article
Neurosciences
Teodora Trendafilova, Kaustubh Adhikari, Annina B. Schmid, Ryan Patel, Erika Polgar, Kim Chisholm, Steven J. Middleton, Kieran Boyle, Allen C. Dickie, Evangelia Semizoglou, Jimena Perez-Sanchez, Andrew M. Bell, Luis Miguel Ramirez-Aristeguieta, Samar Khoury, Aleksandar Ivanov, Hendrik Wildner, Eleanor Ferris, Juan-Camilo Chacon-Duque, Sophie Sokolow, Mohamed A. Saad Boghdady, Andre Herchuelz, Pierre Faux, Giovanni Poletti, Carla Gallo, Francisco Rothhammer, Gabriel Bedoya, Hanns Ulrich Zeilhofer, Luda Diatchenko, Stephen B. McMahon, Andrew J. Todd, Anthony H. Dickenson, Andres Ruiz-Linares, David L. Bennett
Summary: Repeated application of noxious stimuli leads to increased pain perception, which is associated with genetic variations in the sodium-calcium exchanger type 3 (NCX3) gene. Lack of NCX3 results in hypersensitivity to the second phase of stimulation, slowed calcium clearance, and increased wind-up. The study identifies Ca2+ efflux as a pathway underlying temporal summation and persistent pain.
Article
Neurosciences
Maria Gutierrez-Mecinas, Eva Kokai, Erika Polgar, Raphaelle Quillet, Heather F. Titterton, Greg A. Weir, Masahiko Watanabe, Andrew J. Todd
Summary: Peptide (GRP) in the spinal dorsal horn acts on the GRP receptor and is implicated in itch. The source of GRP in the dorsal horn is not fully understood. Two antibodies against pro-GRP were developed, and they reliably detected GRP-expressing neurons and axons, indicating that excitatory interneurons expressing NPFF or substance P are likely to be the main source of GRP in the spinal dorsal horn.
Article
Biology
Amy Cheung, Kotaro Konno, Yuka Imamura, Aya Matsui, Manabu Abe, Kenji Sakimura, Toshikuni Sasaoka, Takeshi Uemura, Masahiko Watanabe, Kensuke Futai, Nils Brose
Summary: The study reveals the involvement of Nrxn genes in the modulation of 5-HT transmission and behavior, suggesting a potential link between Nrxn mutations and ASD.
Article
Biology
Remi Ronzano, Sophie Skarlatou, Bianca K. Barriga, B. Anne Bannatyne, Gardave Singh Bhumbra, Joshua D. Foster, Jeffrey D. Moore, Camille Lancelin, Amanda M. Pocratsky, Mustafa Goerkem Ozyurt, Calvin Chad Smith, Andrew J. Todd, David J. Maxwell, Andrew J. Murray, Samuel L. Pfaff, Robert M. Brownstone, Niccolo Zampieri, Marco Beato
Summary: In this study, multiple viral-tracing methods were used to investigate the organization of premotor interneurons contacting motor pools controlling flexion and extension of the ankle. Contrary to expectations, it was found that these premotor interneurons are highly intermingled with motor neurons, suggesting the absence of clear spatial patterns in the processing of motor instructions.
Article
Multidisciplinary Sciences
Raphaelle Quillet, Allen C. Dickie, Erika Polgar, Maria Gutierrez-Mecinas, Andrew M. Bell, Luca Goffin, Masahiko Watanabe, Andrew J. Todd
Summary: Excitatory interneurons in the superficial dorsal horn (SDH) include a class known as vertical cells that express neuropeptide FF (NPFF). There is considerable overlap between these NPFF cells and a population of neurons that express the gastrin-releasing peptide receptor (GRPR). However, NPFF cells differ from GRPR cells in terms of dendritic spine density, electrical excitability, and NPY Y1 receptor response, suggesting at least two distinct classes of vertical cells with differing roles in somatosensory processing.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Kieran A. Boyle, Erika Polgar, Maria Gutierrez-Mecinas, Allen C. Dickie, Andrew H. Cooper, Andrew M. Bell, Evelline Jumolea, Adrian Casas-Benito, Masahiko Watanabe, David I. Hughes, Gregory A. Weir, John S. Riddell, Andrew J. Todd
Summary: This study investigates the role of interneurons that continue to express neuropeptide Y (NPY-INs) in the adult mouse spinal cord. The findings suggest that activation of NPY-INs reduces acute pain and pruritogen-evoked itch, while silencing them causes exaggerated itch responses. Silencing another population of inhibitory interneurons also increases itch, but to a lesser extent.
Article
Multidisciplinary Sciences
Kohtarou Konno, Miwako Yamasaki, Taisuke Miyazaki, Masahiko Watanabe
Summary: The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to buried target molecules. To solve this problem, we used glyoxal as a fixative, which greatly improved antibody penetration, uncovering signals for buried molecules. Glyoxal also enhanced immunosignals of most other molecules, including the controversial synaptic adhesion molecule Neuroligin 1.
Article
Medicine, Research & Experimental
Tyler S. Nelson, Heather N. Allen, Paramita Basu, Pranav Prasoon, Eileen Nguyen, Cynthia M. Arokiaraj, Diogo F. S. Santos, Rebecca P. Seal, Sarah E. Ross, Andrew J. Todd, Bradley K. Taylor
Summary: Neuropeptide Y targets the Y1 receptor to produce analgesia in the spinal dorsal horn. The Y1-INs, which express the Y1 receptor, are necessary and sufficient for neuropathic hypersensitivity. This study identified three subpopulations of Y1-INs based on their coexpression with gastrin releasing peptide, neuropeptide FF, and cholecystokinin. Among these subpopulations, the Grp/Npy1r-INs were found to be conserved in higher order mammalian species and may represent a promising target for the treatment of neuropathic pain.
Article
Multidisciplinary Sciences
Hitomi Sasamori, Toshiaki Asakura, Chiaki Sugiura, Youcef Bouchekioua, Naoya Nishitani, Masaaki Sato, Takayuki Yoshida, Miwako Yamasaki, Akira Terao, Masahiko Watanabe, Yu Ohmura, Mitsuhiro Yoshioka
Summary: This study examined the role of dopamine D-5 receptors in impulse control and found that they are not necessary for impulse control. The results highlight the importance of time series analysis and detailed analysis of the learning process in understanding the behavioral functions of D-5 receptors.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.