Research activity

Sandvig Group – Integrative Neuroscience

 

Foto: Jens Børtveit/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

  1. Are there specific network topologies that enable optimal functional output?
  2. 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?
  3. 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

Current external students

  • Shi-qi Zhang, PhD candidate Fine-tuning the NAD+-UPRmt and the NAD+- circadian axes to slow down Alzheimer's Disease, Department of Clinical Molecular Biology, Akershus University Hospital, Faculty of Medicine University of Oslo (thesis submitted for evaluation January 2025)
  • Trym Lindell, PhD candidate, Department of Computer Science, OsloMet; Neural reservoirs and hybrid computing 
  • Martinius Knudsen, PhD candidate, Department of Engineering Cybernetics, NTNU. Training and modeling of biological networks

Alumni

Alumni

  • Nicolai Winter-Hjelm, INB, NTNU. PhD in Medicine and Health Sciences. Bioengineered Neural Networks as Computational Systems – Designing Anatomically Inspired Microcircuit to Decode Neural Function and Dysfunction. ISBN 978-82-326-8299-7
  • Lars Erik Schiro, INB, NTNU. PhD in Medicine and Health Sciences. A Regenerative Crossroad within the Niche: The Role of Neural Stem Cells in Traumatic CNS Injury. ISBN 978-82-326-7896-9
  • Janelle Shari Weir, INB, NTNU. PhD in Medicine and Health Sciences. Motifs of Order – Emergent Self-Organization and Complex Dynamics in Biological Neural Networks. ISBN 978-82-326-7676-7
  • Marie Wahlstrøm, Investigating PACMA31 as a Potential Inhibitor for NO-Induced Growth Cone Collapse of In Vitro Neural Networks, MSc in Biotechnology, INB, NTNU 
  • Mari Susanne Ås Røberg, Combinatorial Treatment with Hydroxyfasudil and Lonafarnib of Healthy and Aβ-induced in vitro Neuronal Networks, MSc in Molecular Medicine, INB, NTNU
  • Vegard Fiskum, INB, NTNU. PhD in Medicine and Health Sciences. Increased Cost of Living. Network Scale Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis. ISBN 978-82-326-7225-7
  • Katrine Sjaastad Hanssen, KISN & INB, NTNU. PhD in Medicine and Health Sciences. Dissecting the Complexities of Alzheimer´s Disease – Engineering Selectively Vulnerable Neural Networks In Vitro. ISBN 978-82-326-7430-5
  • Trym Lindell, PhD in Computer Science, NTNU & OsloMet. Optimization of dynamical systems towards criticality and intelligent behavior. ISBN 978-82-326-6953-0
  • Kristine Heiney, PhD in Computer Science, NTNU & OsloMet. Deciphering and emulating neuronal communication: Population-level computation from elemental interactions. 
  • Marthe Bendiksvoll Grønlie, Adapting Advanced Cellular Models to Patient-Derived Cells for Studying Neurodegenerative Disease, MSc in Neuroscience, INB, NTNU
  • Polina Malahov, Advanced neuroengineering for studying the structure-function dynamics in healthy and perturbed neural networks. MSc in Neuroscience, INB, NTNU
  • Riccardo Iandolo, Postdoc (2021-2023), INB, NTNU. PROTEQT
  • Ola Huse Ramstad, Postdoc (2021-2023), INB, NTNU & OsloMet. Deep Cellular Automata
  • 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
  • Eero Kalevi Kibur, MSc in Neuroscience, INB, NTNU. Network dysfunction in the cortico- entorhinal-hippocampal networks in the predementia stage of Alzheimer’s disease. BDNF and aberrant network activity
  • 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)

person-portlet

Group leaders

Axel Sandvig
Axel Sandvig
Professor
axel.sandvig@ntnu.no
Ioanna Sandvig
Ioanna Sandvig
Professor
ioanna.sandvig@ntnu.no

PRESTEP

PRESTEP

Predisposing factors for post-stroke epilepsy

The MemAD Study

The MemAD Study

Research in the fight against Alzheimer's

person-portlet

Sandvig group members