{"entity": "journal", "iuid": "f3188b52866f40beaf303d123ae3418c", "timestamp": "2026-07-13T10:10:42.209Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/J.%20Neurosci..json"}, "display": {"href": "https://publications.scilifelab.se/journal/J.%20Neurosci."}}, "title": "J. Neurosci.", "issn": "1529-2401", "issn-l": "0270-6474", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "e3725231fdc4443b9e05cdcebf511589", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e3725231fdc4443b9e05cdcebf511589.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e3725231fdc4443b9e05cdcebf511589"}}, "title": "Excitatory Spinal Lhx9-Derived Interneurons Modulate Locomotor Frequency in Mice.", "authors": [{"family": "Bertho", "given": "Ma\u00eblle", "initials": "M", "orcid": "0000-0002-5544-3808", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4a316caf884b82bef2ae5d416b3c26.json"}}, {"family": "Caldeira", "given": "Vanessa", "initials": "V"}, {"family": "Hsu", "given": "Li-Ju", "initials": "L"}, {"family": "L\u00f6w", "given": "Peter", "initials": "P", "orcid": "0000-0002-1948-0951", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1decd963894d5ea2facada6a6926c5.json"}}, {"family": "Borgius", "given": "Lotta", "initials": "L"}, {"family": "Kiehn", "given": "Ole", "initials": "O", "orcid": "0000-0002-5954-469X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a9f92b042b94b859fd9c4cebac64b8c.json"}}], "type": "journal article", "published": "2024-05-01", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "issn-l": "0270-6474", "volume": "44", "issue": "18", "pages": null}, "abstract": "Locomotion allows us to move and interact with our surroundings. Spinal networks that control locomotion produce rhythm and left-right and flexor-extensor coordination. Several glutamatergic populations, Shox2 non-V2a, Hb9-derived interneurons, and, recently, spinocerebellar neurons have been proposed to be involved in the mouse rhythm generating networks. These cells make up only a smaller fraction of the excitatory cells in the ventral spinal cord. Here, we set out to identify additional populations of excitatory spinal neurons that may be involved in rhythm generation or other functions in the locomotor network. We use RNA sequencing from glutamatergic, non-glutamatergic, and Shox2 cells in the neonatal mice from both sexes followed by differential gene expression analyses. These analyses identified transcription factors that are highly expressed by glutamatergic spinal neurons and differentially expressed between Shox2 neurons and glutamatergic neurons. From this latter category, we identified the Lhx9-derived neurons as having a restricted spinal expression pattern with no Shox2 neuron overlap. They are purely glutamatergic and ipsilaterally projecting. Ablation of the glutamatergic transmission or acute inactivation of the neuronal activity of Lhx9-derived neurons leads to a decrease in the frequency of locomotor-like activity without change in coordination pattern. Optogenetic activation of Lhx9-derived neurons promotes locomotor-like activity and modulates the frequency of the locomotor activity. Calcium activities of Lhx9-derived neurons show strong left-right out-of-phase rhythmicity during locomotor-like activity. Our study identifies a distinct population of spinal excitatory neurons that regulates the frequency of locomotor output with a suggested role in rhythm-generation in the mouse alongside other spinal populations.", "doi": "10.1523/JNEUROSCI.1607-23.2024", "pmid": "38438260", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service", "Bioinformatics Long-term Support WABI": "Service", "Bioinformatics Support, Infrastructure and Training": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11063822"}, {"db": "pii", "key": "JNEUROSCI.1607-23.2024"}], "notes": [], "created": "2025-02-28T14:23:29.617Z", "modified": "2025-11-28T19:35:42.692Z"}, {"entity": "publication", "iuid": "9307e704e3a74ee58608adb1be1471ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9307e704e3a74ee58608adb1be1471ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9307e704e3a74ee58608adb1be1471ef"}}, "title": "A Novel and Functionally Diverse Class of Acetylcholine-Gated Ion Channels.", "authors": [{"family": "Hardege", "given": "Iris", "initials": "I", "orcid": "0000-0001-6063-5954", "researcher": {"href": "https://publications.scilifelab.se/researcher/a834728aae72483083e3727ba2523039.json"}}, {"family": "Morud", "given": "Julia", "initials": "J"}, {"family": "Courtney", "given": "Amy", "initials": "A"}, {"family": "Schafer", "given": "William R", "initials": "WR"}], "type": "journal article", "published": "2023-02-15", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "volume": "43", "issue": "7", "pages": "1111-1124", "issn-l": "0270-6474"}, "abstract": "Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory ion channels with diverse ligand activation properties in Caenorhabditis elegans We identify three channels, LGC-40, LGC-57, and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our new ligand-receptor pairs we uncover the surprising extent to which single neurons in the hermaphrodite nervous system express both excitatory and inhibitory channels, not only for acetylcholine but also for the other major neurotransmitters. The results presented in this study offer new insight into the potential evolutionary benefit of a vast and diverse repertoire of ligand-gated ion channels to generate complexity in an anatomically compact nervous system.SIGNIFICANCE STATEMENT Here we describe the diversity of cholinergic signaling in the nematode Caenorhabditis elegans We identify and characterize a novel family of ligand-gated ion channels and show that they are preferentially gated by choline rather than acetylcholine and expressed broadly in the nervous system. Interestingly, we also identify one channel gated by chemically diverse ligands including acetylcholine and aminergic ligands. By using our new knowledge of these ligand-gated ion channels, we built a model to predict the synaptic polarity in the C. elegans connectome. This model can be used for generating hypotheses on neural circuit function.", "doi": "10.1523/JNEUROSCI.1516-22.2022", "pmid": "36604172", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9962794"}, {"db": "pii", "key": "JNEUROSCI.1516-22.2022"}], "notes": [], "created": "2023-12-01T10:46:20.194Z", "modified": "2023-12-01T10:46:20.230Z"}, {"entity": "publication", "iuid": "aa486f0c6e644777a62dfa8b71c1df52", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa486f0c6e644777a62dfa8b71c1df52.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa486f0c6e644777a62dfa8b71c1df52"}}, "title": "Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to Functional Recovery", "authors": [{"family": "Hakim", "given": "Ramil", "initials": "R"}, {"family": "Zachariadis", "given": "Vasilios", "initials": "V"}, {"family": "Sankavaram", "given": "Sreenivasa Raghavan", "initials": "SR"}, {"family": "Han", "given": "Jinming", "initials": "J"}, {"family": "Harris", "given": "Robert A", "initials": "RA", "orcid": "0000-0003-4990-509X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b0733d3c25145139f42cad897d6726b.json"}}, {"family": "Brundin", "given": "Lou", "initials": "L"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Svensson", "given": "Mikael", "initials": "M"}], "type": "journal-article", "published": "2021-10-06", "journal": {"title": "J. Neurosci.", "issn": "0270-6474", "volume": "41", "issue": "40", "pages": "8441-8459", "issn-l": null}, "abstract": "Microglia are resident myeloid cells of the CNS. Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated microglia (DAM) with a role in neurodegeneration and demyelination. In this study, we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. We find that as a consequence of SCI, baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with striking similarities to previously reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from baseline microglia and strongly enhance recovery of hindlimb locomotor function following injury.SIGNIFICANCE STATEMENT Although disease-associated microglia (DAM) have been the subject of strong research interest during recent years (Keren-Shaul, 2017; Jord\u00e3o, 2019), their cellular origin and their role in \"normal\" acute injury processes is not well understood. Our work directly addresses the origin and the role of DAM in traumatic injury response. Further, we use a microglia depletion model to prove that DAM in spinal cord injury (SCI) are indeed derived from homeostatic microglia, and that they strongly enhance recovery. Thus, in this work we significantly expand the knowledge of immune response to traumatic injury, demonstrate the applicability to human injury via our unique access to injured human spinal cord tissue, and provide the community with a comprehensive dataset for further exploration.", "doi": "10.1523/jneurosci.0860-21.2021", "pmid": "34417326", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8496189"}, {"db": "pii", "key": "JNEUROSCI.0860-21.2021"}], "notes": [], "created": "2022-11-09T16:00:16.686Z", "modified": "2024-01-16T13:48:38.285Z"}, {"entity": "publication", "iuid": "94f294cb977c40bfa353d86973dd9eb8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/94f294cb977c40bfa353d86973dd9eb8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/94f294cb977c40bfa353d86973dd9eb8"}}, "title": "\u00b5 Opioid Receptor Agonism for L-DOPA-Induced Dyskinesia in Parkinson's Disease.", "authors": [{"family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "researcher": {"href": "https://publications.scilifelab.se/researcher/c33e3029113549ea96e60c7952e5a19a.json"}}, {"family": "Li", "given": "Qin", "initials": "Q"}, {"family": "Hulme", "given": "Heather", "initials": "H"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Pioli", "given": "Elsa", "initials": "E"}, {"family": "Andren", "given": "Per E", "initials": "PE"}, {"family": "Crossman", "given": "Alan R", "initials": "AR"}], "type": "journal article", "published": "2020-08-26", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "volume": "40", "issue": "35", "pages": "6812-6819", "issn-l": "0270-6474"}, "abstract": "Parkinson's disease (PD) is characterized by severe locomotor deficits and is commonly treated with the dopamine precursor L-DOPA, but its prolonged usage causes dyskinesias referred to as L-DOPA-induced dyskinesia (LID). Several studies in animal models of PD have suggested that dyskinesias are associated with a heightened opioid cotransmitter tone, observations that have led to the notion of a LID-related hyperactive opioid transmission that should be corrected by \u00b5 opioid receptor antagonists. Reports that both antagonists and agonists of the \u00b5 opioid receptor may alleviate LID severity in primate models of PD and LID, together with the failure of nonspecific antagonist to improve LID in pilot clinical trials in patients, raises doubt about the reliability of the available data on the opioid system in PD and LID. After in vitro characterization of the functional activity at the \u00b5 opioid receptor, we selected prototypical agonists, antagonists, and partial agonists at the \u00b5 opioid receptor. We then showed that both oral and discrete intracerebral administration of a \u00b5 receptor agonist, but not of an antagonist as long thought, ameliorated LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned female macaque model of PD and LID. The results call for a reappraisal of opioid pharmacology in the basal ganglia as well as for the development of brain nucleus-targeted \u00b5 opioid receptor agonists.SIGNIFICANCE STATEMENT \u00b5 opioid receptors have long been considered as a viable target for alleviating the severity of L-DOPA-induced hyperkinetic side effects, induced by the chronic treatment of Parkinson's disease motor symptoms with L-DOPA. Conflicting results between experimental parkinsonism and Parkinson's disease patients, however, dampened the enthusiasm for the target. Here we reappraise the pharmacology and then demonstrate that both oral and discrete intracerebral administration of a \u00b5 receptor agonist, but not of an antagonist as long thought, ameliorates LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease, calling for a reappraisal of the opioid pharmacology as well as for the development of brain nucleus-targeted \u00b5 receptor agonists.", "doi": "10.1523/JNEUROSCI.0610-20.2020", "pmid": "32690616", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pii", "key": "JNEUROSCI.0610-20.2020"}, {"db": "pmc", "key": "PMC7455220"}], "notes": [], "created": "2021-03-26T12:45:05.245Z", "modified": "2021-12-03T11:51:13.509Z"}, {"entity": "publication", "iuid": "7b1d9e0720374cf5905addfea62090f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7b1d9e0720374cf5905addfea62090f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7b1d9e0720374cf5905addfea62090f5"}}, "title": "Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate \u03b1-Synuclein Disrupted Gene Expression.", "authors": [{"family": "Volakakis", "given": "Nikolaos", "initials": "N"}, {"family": "Tiklova", "given": "Katarina", "initials": "K"}, {"family": "Decressac", "given": "Mickael", "initials": "M"}, {"family": "Papathanou", "given": "Maria", "initials": "M"}, {"family": "Mattsson", "given": "Bengt", "initials": "B"}, {"family": "Gillberg", "given": "Linda", "initials": "L"}, {"family": "Nobre", "given": "Andr\u00e9", "initials": "A"}, {"family": "Bj\u00f6rklund", "given": "Anders", "initials": "A"}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2015-10-21", "journal": {"volume": "35", "issn": "1529-2401", "issue": "42", "pages": "14370-14385", "title": "J. Neurosci.", "issn-l": "0270-6474"}, "abstract": "\u03b1-synuclein, a protein enriched in Lewy bodies and highly implicated in neurotoxicity in Parkinson's disease, is distributed both at nerve terminals and in the cell nucleus. Here we show that a nuclear derivative of \u03b1-synuclein induces more pronounced changes at the gene expression level in mouse primary dopamine (DA) neurons compared to a derivative that is excluded from the nucleus. Moreover, by RNA sequencing we analyzed the extent of genome-wide effects on gene expression resulting from expression of human \u03b1-synuclein in primary mouse DA neurons. The results implicated the transcription factor Nurr1 as a key dysregulated target of \u03b1-synuclein toxicity. Forced Nurr1 expression restored the expression of hundreds of dysregulated genes in primary DA neurons expressing \u03b1-synuclein, and therefore prompted us to test the possibility that Nurr1 can be pharmacologically targeted by bexarotene, a ligand for the retinoid X receptor that forms heterodimers with Nurr1. Although our data demonstrated that bexarotene was ineffective in neuroprotection in rats in vivo, the results revealed that bexarotene has the capacity to coregulate subsets of Nurr1 target genes including the receptor tyrosine kinase subunit Ret. Moreover, bexarotene was able to restore dysfunctional Ret-dependent neurotrophic signaling in \u03b1-synuclein-overexpressing mouse DA neurons. These data highlight the role of the Nurr1-Ret signaling pathway as a target of \u03b1-synuclein toxicity and suggest that retinoid X receptor ligands with appropriate pharmacological properties could have therapeutic potential in Parkinson's disease.\n\nHow \u03b1-synuclein, a protein enriched in Lewy bodies in Parkinson's disease, is causing neuropathology in dopamine neurons remains unclear. This study elucidated how \u03b1-synuclein is influencing gene expression and how Nurr1, a transcription factor known to protect dopamine neurons against \u03b1-synuclein toxicity, can counteract these effects. Moreover, given the protective role of Nurr1, this study also investigated how Nurr1 could be pharmacologically targeted via bexarotene, a ligand of Nurr1's heterodimerization partner retinoid X receptor (RXR). The results showed that RXR ligands could increase neurotrophic signaling, but provided a mixed picture of its potential in a Parkinson's disease rat model in vivo. However, this study clearly emphasized Nurr1's neuroprotective role and indicated that other RXR ligands could have therapeutic potential in Parkinson's disease.", "doi": "10.1523/JNEUROSCI.1155-15.2015", "pmid": "26490873", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "35/42/14370"}], "notes": [], "created": "2017-05-02T12:58:52.960Z", "modified": "2020-01-21T13:56:03.190Z"}], "created": "2017-05-09T09:12:08.033Z", "modified": "2020-11-27T13:14:04.671Z"}