Sandvig
Sandvig Group – Integrative Neuroscience
Foto: Nicolai Winter-Hjelm/NTNU
Our group integrates advanced interdisciplinary theoretical concepts and state-of-the-art methodology to model and investigate neural network behaviour in healthy and perturbed conditions, both in preclinical models and in the clinic.
Aim
To identify and selectively engage key aspects of complex neural network behaviour that determine adaptive or maladaptive neuroplasticity in the lesioned CNS with a view to clinical translation.
Background
CNS lesions as a result of trauma, stroke, or neurodegenerative disease lead to severe and, in most part, irreversible functional deficits. In order to develop appropriate interventions that can help restore lost function, we need to understand how neural networks and circuits reconfigure their structure-function relationships in response to perturbation. Furthermore, we need to be able to distinguish between adaptive and maladaptive neuroplasticity. A corollary to the above is ability to infer network states and to make predictions about network responses to lesion-related pathology or to intervention. The latter is of fundamental importance for determining optimal time and mode of rescue strategy.
Our group integrates advanced interdisciplinary theoretical concepts and state-of-the-art methodology to model and investigate neural network behaviour in healthy and perturbed conditions, both in preclinical models and in the clinic.
Key research questions
- Are there specific network topologies that enable optimal functional output?
- How do neural networks dynamically alter their structure and function in response to perturbation; how do underlying micro- and mesoscale reconfigurations, including changes in synaptic transmission, impact network and circuit function at the macroscale?
- Is it possible to infer internal computational dynamics in the absence of clear, observable external behavioural correlates?
Tools and methods
Main research methods and tools applied in our group include animal models of neurodegenerative disease and traumatic injury, longitudinal in vivo brain microdialysis, cognitive testing, in vitro neuron-, disease-, and patient-specific modelling, electrophysiology, selective manipulation of neuronal assemblies in vitro and in vivo using designer opto-and chemogenetic tools, clinical neuroimaging and transcriptomics, and computational modelling focused on connectomics.
Research
To address our key research questions, we need clinically relevant, robust preclinical models with high predictive validity.
In our current in vivo models, we aim to characterize cellular and systems level responses to pathological perturbations and to determine how induced or inherent lesions affect interconnected networks. We are particularly interested in microscale modifications in neurons and synapses as well as mesoscale alterations in local and downstream connectivity in response to a developing pathology or intervention.
Similarly, in our advanced in vitro neuron-specific and network models we study disease pathogenesis and spread as well as relevant neuroplasticity mechanisms at the micro- and mesoscale. The strength of the in vitro approach lies in our ability to recapitulate and exploit fundamental attributes of biological neural networks, including self-organization over time into assemblies of increasing structural complexity, with concomitant emergence of complex functional dynamics. Furthermore, the approach enables the selective study and manipulation of neurons and networks of interest, including patient-specific ones, to initiate or reverse the pathological cascade.
In vitro and in vivo modelling thus work in tandem and constitute complementary or alternative approaches, depending on the specific research question under investigation, with direct relevance to clinical studies, including ongoing clinical connectomics research by our group. Combined with computational modelling, this integrated multidisciplinary research approach aims to extract structure-function states that may predict future network behaviour, identify critical vulnerability states at the neuronal population level, and also decode or predict adaptive/maladaptive responses to underlying pathology or therapeutic intervention. The latter is of crucial importance, given that maladaptive responses may spread pathology throughout a network, whereas network re-organization might constrain adaptive processes that promote recovery.
Such investigations are of fundamental importance for the characterization and elucidation of pathophysiological processes underlying CNS lesions and also for the generation of new hypotheses about underlying mechanistic causes of lesion trigger and/or spread. The relevant knowledge can thus have a significant impact in achieving genuine clinical translation, for example, by enabling early diagnosis of neurodegenerative disease such as Alzheimer´s disease or ALS. Coupling some of these principles with emerging neurotechnologies can also lead to tailored treatment and rehabilitation paradigms for stroke or spinal cord inured patients.
Current external students
- Katrine Sjaastad Hansen, PhD candidate, Kavli Institute for Systems Neuroscience, NTNU. Developing a novel platform to study Alzheimer ́s disease-relevant neuronal networks in vitro
- Trym Lindell, PhD candidate, Department of Computer Science, OsloMet; Neural reservoirs and hybrid computing
- Kristine Heiney, OsloMet, PhD candidate, Department of Computer Science, OsloMet. Self-Organizing Models of Artificial learning in neural substrates, toward strategies to restore perturbed dynamics
- Sidney Pontes-Filho, PhD candidate, Department of Computer Science, OsloMet. EVODynamic: Evolution of discreet dynamic systems for modelling computational systems based on self- organisation through local interactions
- Martinius Knudsen, PhD candidate, Department of Engineering Cybernetics, NTNU. Training and modeling of biological networks
Alumni
- Ulrich Stefan Bauer, INB, NTNU. PhD in Medicine and Health Sciences. Advanced Cellular Models for the Recapitulation and Study of Neuropathology. ISBN 978-82-326-5590-8
- Christiana Bjørkli, INB, NTNU. PhD in Medicine and Health Sciences. The Inside-Out of Alzheimer´s Disease. ISBN 978-82-326-5894-7
- Emily Karabeika, MSc in Neuroscience, INB, NTNU. Co-culture of humanized Apolipoprotein E astrocytes with primary entorhinal cortex neurons from adult mice and hippocampal neurons from embryonic rats
- Salome Nora Niethammer, MSc in Neuroscience, Kavli Institute for Systems Neuroscience, NTNU. Extraction and co-culturing of adult hippocampal and entorhinal neurons from Alzheimer model-animals (co-supervised project)
- Åste Brune Tomren, MSc in Nanotechnology, Department of Physics, NTNU. Using microfluidics and 3D surfaces to increase the physiological translatability of in vitro neural networks (co-supervised project)
- Nora Cecilie Ebbesen, INB, NTNU. MSc in Neuroscience. Inhibiting the neuronal region with initial neurodegeneration in a mouse model of Alzheimer´s disease; effects on neuropathology and behaviour
- Mary Elizabeth Hemler, INB, NTNU. MSc in Neuroscience. Using microdialysis to administer and assess drugs aimed at attenuating Alzheimer´s disease neuropathology
- Sondre Valentin Jordbræk, INB, NTNU, MSc in Neuroscience. Self-organized Criticality in engineered in vitro networks; A balance of excitation and inhibition
- Nienke Laura de Jong, Department of Physics, NTNU, MSc in Nanotechnology. Specialization project: Developing an in vitro microfluidic neural network model with unidirectional axonal growth (co-supervised project)
- Leik Bjelland Isdal, Department of Physics, NTNU, MSc in Nanotechnology. Developing nanoscale surface topography on a brain-on-chip platform to mimic the physiological conditions of the in vivo brain (co-supervised project)
- Edevard Brekke Hvide, Dept. of Physics, NTNU. MSc in Nanotechnology, Sikorski group. Unidirectional axon growth in vitro (co-supervised project)
Salvatore Castelbuono, MSc in Computer Science, Barberi group, Politecnico di Milano, Italy. Development of statistical models of neurons able to characterize their firing activity (co-supervised project
- Vibeke Devold Valderhaug, INB, NTNU, PhD in Medicine. Structure-function relationships in biological neural networks and the influence of neurodegenerative processes on such dynamics. ISBN 978-82-326-4506-0
- Ola Huse Ramstad, INB, NTNU, PhD in Medicine. Neural Disorder at the Edge-of-Chaos. ISBN 978-82-326- 4924-2
- Anna Mikalsen Kollstrøm, INB, NTNU, MSc in Neuroscience. How does ALS pathology spread to affect healthy neurons? Recapitulation of disease progression in multi-nodal neural networks in vitro
- Isak Kyrre Lichtwarck Bjugn, INB, NTNU, MSc in Nanomedicine. Structural effects on the computational capacity of neural networks
- Rikke Bie, INB, NTNU, MSc in Neuroscience. Micro- and mesoscale neuroplasticity of in vitro cortical neuronal networks
- Marit Trones Rem, INB, NTNU, MSc in Neuroscience. Generating neural networks from ependymal cells harvested after spinal cord injury
- Nicolai Winter-Hjelm, IKOM, NTNU, MSc in Nanotechnology. Development of next-generation microfluidic microelectrode arrays (co-supervised project)
- Riccardo Levi, Politecnico di Milano, Italy, MSc in Computer Science. Development of statistical models of neurons able to characterize their firing activity (co-supervised project)
- Torvald Ask, IKOM, NTNU, MSc in Neuroscience. Functional connectivity in in vitro models of X-linked intellectual disability (co-supervised project)
- Rosanne van de Wijdeven, IKOM, NTNU, PhD in Medical Technology. Tailored microfluidic platforms for advanced neurobiology, neuroengineering, and electrophysiology. NTNU;2019:135 (co-supervised project)
- Irene Busti, PhD in Neuroscience, Institute of Neuroscience, CNR, Pisa, Italy. Project: Development of in vitro modelling platform to investigate the neural network response to ischemic injury (7- month research stay, INB, NTNU)
- Janelle Shari Weir, INB, NTNU, MSc in Neuroscience. Structural and functional dynamics of healthy and perturbed neural networks in vitro
- Katrine Sjaastad Hanssen, Kavli Institute for Systems Neuroscience, NTNU, MSc in Neuroscience. Establishing lateral entorhinal cortex layer II- neuron cultures as a tool for the investigation of early Alzheimer ́s disease related changes (co-supervised project)
- Sigrún Jarlsdóttir, INB, NTNU, MSc in Neuroscience. Investigation of axonal and synaptic plasticity in an in vitro model of spinal cord injury and repair
- Guillaume Vignolle, MSc in Computer Science, Erasmus programme student, ENSTA ParisTech, France. Project: Evolution in Materio paradigm for solving a simple computational task (3-month research stay; co-supervised project)
- Ingrid Lovise Augestad, INB, NTNU, PhD in Neuroscience. In situ tissue engineering and induced plasticity in experimental stroke. ISBN 978-82-326-3080-6
- Vanessa Crain, INB, NTNU, MSc in Neuroscience. Replicating ischemic stroke in vitro
- Jonas Haldoupis, INB, NTNU, MSc in Neuroscience. Modelling pathophysiological features of spinal cord injury in 2D and 3D cell cultures
- Nikolas Haldoupis, INB, NTNU, MSc in Neuroscience. In vitro mimicking and targeting of neurodegenerative mechanisms relevant to amyotrophic lateral sclerosis
- Ola Huse Ramstad, INB, NTNU. MSc in Neuroscience, Developing long-term in vitro microculture for neuropathology modelling
- Peter Aaser, Department of Computer Science, NTNU. MSc in Computer Science. Investigating in-vitro neuron cultures as computational reservoir (co-supervised project)
- Barbora Svobodova, PhD in Neuroscience, Charles University, Prague, Czech Republic. Project: In situ tissue engineering strategies for spinal cord repair (visiting student; 3-month research stay)
- Kristina Karova, PhD in Neuroscience, Charles University, Prague, Czech Republic. Project: In situ tissue engineering strategies for spinal cord repair (visiting student; 3-month research stay)
Sandvig group members
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Esin Avci Colak PhD Candidate
esin.avci@ntnu.no Department of Neuromedicine and Movement Science -
Morisha Balakumar Medical Research Student
morisha.balakumar@ntnu.no MH Faculty Administration -
Christiana Lucinda Bjørkli Postdoctoral researcher
+4741544063 christiana.bjorkli@ntnu.no Department of Neuromedicine and Movement Science -
Nicholas Christiansen PhD Candidate
nicholas.christiansen@ntnu.no Department of Neuromedicine and Movement Science -
Natan Derek Postdoctoral Fellow
natan.derek@ntnu.no Department of Neuromedicine and Movement Science -
Vegard Fiskum PhD Candidate
+4790012644 vegard.fiskum@ntnu.no Department of Neuromedicine and Movement Science -
Marthe Bendiksvoll Grønlie PhD Candidate at Sandvig Group of Integrative Neuroscience
+4748601545 marthe.b.gronlie@ntnu.no Department of Neuromedicine and Movement Science -
Katrine Sjaastad Hanssen Researcher
+4790705845 katrine.s.hanssen@ntnu.no Department of Neuromedicine and Movement Science -
Anna Mikalsen Kollstrøm PhD Candidate
+4795485402 anna.m.kollstrom@ntnu.no Department of Neuromedicine and Movement Science -
Ola Huse Ramstad
ohramstad@gmail.com Department of Neuromedicine and Movement Science -
Axel Sandvig Professor
axel.sandvig@ntnu.no Department of Neuromedicine and Movement Science -
Ioanna Sandvig Professor
ioanna.sandvig@ntnu.no Department of Neuromedicine and Movement Science -
Lars Erik Schiro
schiro.larserik146@gmail.com Department of Neuromedicine and Movement Science -
Varanann Varathalingam Medical Research Student
varananv@stud.ntnu.no -
Janelle Shari Weir
janellew@stud.ntnu.no -
Nicolai Winter-Hjelm Researcher, Ph.D.
+4799010998 nicolai.winter-hjelm@ntnu.no Department of Neuromedicine and Movement Science