Image: Jan ALfredsson, Region Västerbotten
Image: Jan ALfredsson, Region Västerbotten
Strategic research area StratNeuro is a strategic research area established as a collaboration between Karolinska Institute, Umeå University and KTH.
StratNeuro’s vision is to advance knowledge on brain disorders that cause cognitive and sensory-motor dysfunctions by integrating research in basic and clinical neurosciences, and to create an internationally renowned, interactive, translational neuroscience research environment.
Disorders of brain function are among the most common causes of disability in high-income countries. The European Brain Council has estimated that a third of Europe's residents will be affected at some point in their lives.
In addition to the suffering of patients and their families, this leads to enormous costs to society. Despite this, there is a lack of effective preventive methods and treatments. Therefore, Karolinska Institutet has established the strategic research area neuroscience (StratNeuro) together with Umeå University and KTH.
At Umeå University StratNeuro has supported research environments with focus on the corresponding state of the art infrastructures for investigations within three strategic areas, allowing broad possibility for collaborative and interdisciplinary research, along the following research lines:
1. Human Cognitive Neuroscience
3 tesla Magnetic Resonance Imaging (MRI) scanner at the University Hospital, Umeå
ImageMikael StiernstedtStratNeuro supports research on human neuroimaging platforms employing Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and hybrid PET-MRI connected to the Umeå center for Functional Brain Imaging, UFBI.
Research at UFBI investigates the neural basis of human cognition in health, aging, and disease, as well as translational research with a cognitive neuroscience focus. The human neuroimaging platforms are also used by several clinical and preclinical projects. A list of affiliated researchers using the UFBI neuroimaging infrastructure. Several prominent neuroimaging cohorts have been collected at UFBI, including the Betula study (functional and structural MRI), the Cobra study (PET and MRI), and the DyNAMiC study (PET and MRI). The Betula study has also been incorporated into the National E-infrastructure for Aging Research (NEAR), and into the PREDICT research initiative (in Swedish) and several international consortia such as Lifebrain and ENIGMA.
Work within StratNeuro aims at strengthening existing and future research activities within human cognitive neuroscience at Umeå University by for instance arranging meetings and workshops, promoting increased interaction between human and animal neuroscience research, encouraging representation of UFBI at national scientific meetings, as well as focusing on strengthening collaborations with KI and KTH.
Selected, recent publications supported by StratNeuro
A full list of research publications from UFBI
2. Physiology and plasticity of brain microcircuits in vivo
Multiphoton network imaging in vivo.
ImagePaolo MediniWe have built in Umeå a new research infrastructure that allows to combine one- and two-photon imaging of neuronal networks with advanced intra- and extra-cellular electrophysiology on one side, and with opto/chemogenetic stimulation (also with multiphoton holography!) on the other side in awake, behaving animals. Virtual reality stimulation, voltage sensitive dye imaging and quantitative neuroanatomy are also available, together with an electro-mechanic workshop.
Result of multiphoton holographic stimulation of neurons expressing the opsin bReaches in vivo.
ImagePaolo MediniThe focus is the understanding of the microcircuit basis of the integrative function of sensory-motor cortical circuits and their plasticity (after learning, or after lesions), in line with the strategic purposes of the StratNeuro project in Umeå. StratNeuro funds are used to cover infrastructural costs (service costs, research engineer time including optical research engineer and programming costs for analysis routines), as well consumable costs to allow use of transgenic lines of mice expressing calcium indicators or opsins in identified cell types (including viral vector production costs).
This research infrastructure is, in its combination of techniques, currently unique in Scandinavia and is open for collaborative efforts for neuroscientists at Umeå University and within the StratNeuro network, but also outside.
Selected, recent publications
Ivica N, Censoni L, Sjöbom J, Richter U, Petersson P. Differential effects of skilled reaching training on the temporal and spatial organization of somatosensory input to cortical and striatal motor circuits. J Neurophysiol. 2022 Jan 1;127(1):225-238. doi: 10.1152/jn.00464.2021. Epub 2021 Dec 22. PMID: 34936519.
Kuznetsova T, Antos K, Malinina E, Papaioannou S, Medini P. Visual stimulation with blue wavelength light drives V1 effectively eliminating stray light contamination during two-photon calcium imaging. J Neurosci Methods. 2021 Oct 1;362:109287. doi: 10.1016/j.jneumeth.2021.109287. Epub 2021 Jul 10. PMID: 34256082.
Tripathi A, Sato SS, Medini P. Cortico-cortical connectivity behind acoustic information transfer to mouse orbitofrontal cortex is sensitive to neuromodulation and displays local sensory gating: relevance in disorders withauditory hallucinations? J Psychiatry Neurosci. 2021 May 27;46(3):E371-E387. doi: 10.1503/jpn.200131. PMID: 34043305; PMCID: PMC8327972.
Andersson B, Tan EP, McGreal SR, Apte U, Hanover JA, Slawson C, Lagerlöf O. O-GlcNAc cycling mediates energy balance by regulating caloric memory. Appetite.2021 Oct 1;165:105320. doi: 10.1016/j.appet.2021.105320. Epub 2021 May 23. PMID: 34029673.
Sjöbom J, Tamtè M, Halje P, Brys I, Petersson P. Cortical and striatal circuits together encode transitions in natural behavior. Sci Adv. 2020 Oct 9;6(41):eabc1173. doi: 10.1126/sciadv.abc1173. PMID: 33036974.
Kokinovic B, Medini P. Loss of GABA<sub>B</sub> -mediated interhemispheric synaptic inhibition in stroke periphery. J Physiol. 2018 May 15;596(10):1949-1964. doi: 10.1113/JP275690. Epub 2018 Apr 17. PMID: 29508394; PMCID: PMC5978350.
A full list of research publications can be found at the lab web sites of the group leaders permanently sharing the infrastructure at the moment:
Collaborations resulting in publications: Anna Berghard, Leif Carlsson, Andrei Chabes, Sjoerd Wanrooij, Nasim Sabouri.
3. Neurodegeneration at molecular level: ALS research
StratNeuro supports research platforms based on transgenic mice models, both those that have been developed inhouse here in Umeå and those that have been acquired in cooperations with other researchers.
For comparisons with human tissue, we have for our inhouse models access to postmortem material. Thus, our platform forms a world unique resource for investigation into neurodegenerative disease. Transgenic animal models allow the study of molecular details of initiating events in neurodegeneration which are impossible in living humans.
Furthermore, a platform enabling high-precision inoculation experiments to be performed. This enables researchers to precisely define the start of the initiating events and provide a sound basis for testing the effectiveness of interventions. These platforms has been used to ascertain the first description of prion nature of amyotrophic lateral sclerosis induced by mutations in superoxide dismutase-1.
Virtual reality and voltagesensitive imaging.
ImageMatthew MarklundSelected, recent publications
Nordström U, Lang L, Ekhtiari Bidhendi E, Zetterström P, Oliveberg M, Danielsson J, Andersen PM, Marklund SL. Mutant SOD1 aggregates formed in vitro and in cultured cells are polymorphic and differ from those arising in the CNS. J Neurochem 164:1 (2023) 77-93. https://doi.org/10.1111/jnc.15718.
Forsberg, K.M., Graffmo, K.S., Stenvall, E. et al. Widespread CNS pathology in amyotrophic lateral sclerosis homozygous for the D90A SOD1 mutation. Acta Neuropathol 145, 13–28 (2023). https://doi.org/10.1007/s00401-022-02519-z.
Günther, R.; Pal, A.; Williams, C.; Zimyanin, V.L.; Liehr, M.; von Neubeck, C.; Krause, M.; Parab, M.G.; Petri, S.; Kalmbach, N.; Marklund, S.L.; Sterneckert, J.; Munch Andersen, P.; Wegner, F.; Gilthorpe, J.D.; Hermann, A. Alteration of Mitochondrial Integrity as Upstream Event in the Pathophysiology of SOD1-ALS. Cells 2022, 11, 1246. https://doi.org/10.3390/cells11071246.
Shlomit Ezer, Muhannad Daana, Julien H Park, Shira Yanovsky-Dagan, Ulrika Nordström, Adily Basal, Simon Edvardson, Ann Saada, Markus Otto, Vardiella Meiner, Stefan L Marklund, Peter Munch Andersen, Tamar Harel, Infantile SOD1 deficiency syndrome caused by a homozygous SOD1 variant with absence of enzyme activity, Brain, Vol 145:3, March 2022, Pages 872–878, https://doi.org/10.1093/brain/awab416
Keskin I, Ekhtiari Bidhendi E, Marklund M, Andersen PM, Brännström T, Marklund SL. Nordström U. Peripheral administration of SOD1 aggregates does not transmit pathogenic aggregation to the CNS of SOD1 transgenic mice. Acta Neuropathologica Communications vol 9, 111 (2021) https://doi.org/10.1186/s40478-021-01211-9
StratNeuro’s 1-year grant is awarded to Professor Johan Holmberg, Department of Molecular Biology.
