Fisahn Laboratory

In our lab we study mechanisms of neuronal synchronization and functional dynamics of neuronal networks that form the basis for our brain’s cognitive ability.

Background

Rhythmic electrical activity in neuronal networks (network oscillations) is important for many higher functions in the brain, such as learning, memory and cognition. Such activity can be classed into different frequency bands, which are implicated in distinct processes and behaviors. In addition, network oscillations are altered or disrupted by various disorders of the nervous system such as Alzheimer's disease, schizophrenia and epilepsy, which can result in cognitive or behavioral impairments.

Research focus

The overall aim of our work is to help explain on a cellular, synaptic and network level the clinically-documented changes of rhythmic network activity caused by various brain disorders that result in cognitive decline and memory deficits in patients. We focus on functional network dynamics and mechanisms of neuronal synchronization in physiological conditions as well as in animal models of neurodegenerative and neuropsychiatric disorders with the aim to identify and validate potential targets for therapeutic intervention and restoration of cognitive function.

Our core hypothesis postulates that changes to the electrical behavior of neurons and neuronal networks are the first functional impairments in disorders that lead to cognitive decline, and as such are a very reliable functional biomarker. Our work has shown that such functional changes far precede the accumulation of disease-typical classical biomarkers such as amyloid-beta in Alzheimer's disease or alpha-synuclein in Parkinson's disease.

We are particularly interested in the role of fast-spiking interneurons, which experience action potential de-synchronization in disease assays very early on. We believe that rescuing this de-synchronization and restoring normal neuronal network function is the key to identify efficacious treatments for cognitive brain disorders.

Research Assays

  • Mice (wild-type, various disease model strains, etc.)
  • Human iPS cell lines from patients with diseases of interest
  • Drosophila fly strains expressing constructs of interest

Research Methods

  • Electrophysiology and Optophysiology in acute brain slice preparations
  • Electrophysiology and Optophysiology in acute and iPS cell cultures
  • Mouse drug treatment trials
  • Mouse behavioral testing
  • Immunohistochemistry
  • Drosophila behavioral testing (in collaboration)
  • Neuron and neuronal network computer modelling (in collaboration)
  • Drug discovery (in collaboration)

Main ongoing research projects

  1. Rescue of synaptic, network and cognitive impairment in neurodegenerative diseases such as Alzheimer’s and Parkinson’s by modulation of neuronal calcium homeostasis.
  2. Rescue of synaptic, network and cognitive impairment in neuropsychiatric diseases such as schizophrenia by modulation of neuronal calcium homeostasis.
  3. Investigation and treatment of neuronal network alterations responsible for cognitive late effects following cranial radiotherapy.
  4. Investigation of the role of fast-spiking interneurons in hippocampus and neocortex for cognition-relevant neuronal network activity.
  5. Investigation of functional differences of pyramidal cell subpopulations during cognition-relevant neuronal network activity in hippocampus.
  6. Rescue of synaptic, network and cognitive impairment in neurodegenerative diseases by interference with aggregation of amyloidogenic peptides.

    Group members

    Present members

    Arturo Gonzalez Isla

    Postdoctoral studies

    Past members

    Dr. Hugo Balleza-Tapia

    Dr. Pablo Dolz-Gaitón

    Dr. Fengna Chu

    Dr. Richard Andersson

    Dr. Misha Zilberter

    Dr. Alicia Stradomska

    Dr. Richardon Leao

    Dr. Manisha Chugh

    Dr. Daniela Papadia

    Dr. Firoz Roshan Kurudenkandy

    Dr. April Johnston

    Dr. Hui Min Tan

    Dr. Sophie Crux

    Ms Daniela Wikström

    Funding

    Current funding

    • Alzheimerfonden
    • Hjärnfonden
    • StratNeuro - The Strategic Research Program in Neuroscience at Karolinska Institutet
    • EU EUROSTAR European consortium grant
    • Karolinska Institutet
    • KI-NIH Graduate Partnership Program
    • CONACYT Postdoctoral Program (Mexico)

    Previous funding

    • EU FP7 IMBRAIN project
    • EU Marie-Curie Postdoctoral Program
    • Swedish Medical Research Council (VR-M)
    • Stockholm Brain Institute (SBI)
    • Human Frontier Science Program (HFSP)
    • Åke Wiberg Foundation
    • Network of European Neuroscience Institutes (ENI-net)
    • Jeanssons Stiftelser
    • Ahlén Stiftelsen
    • VINNOVA
    • Parkinsonfonden
    • H. Lundbeck A/S, Denmark (industry collaboration)
    • Osterman Foundation
    • Stiftelsen för Gamla Tjänarinnor

    Selected scientific publications

     

    L Arroyo-García, A Gonzales-Isla, Y Andrade-Talavera, H Balleza-Tapia, R Loera-  Valencia, L Alvarez-Jimenez, S Tambaro, P Nilsson & A Fisahn (2021) 
    Amyloid-β-induced desynchronization of fast-spiking interneurons as the earliest functional impairment in Alzheimer’s Disease. 
    Molecular Psychiatry (accepted)            

    Balleza-Tapia H, Arroyo-García LE, Isla AG, Loera-Valencia R & Fisahn A (2021)
    Functional differences of three pyramidal cells subpopulations during gamma oscillations displaying specific excitatory/inhibitory input profiles in hippocampal CA3 area.
    Progress in Neurobiology (accepted)     

    Emre C, Arroyo-García LE, Fisahn A & Schulzberg M. 
    SPM treatment restores cognition-relevant biomarkers and neuronal activity in the AppNL-G-F mouse model of Alzheimer’s Diseases. 
    Communications Biol. (accepted)           

    Andrade-Talavera Y, Chen G, Kurudenkandy FR, Zilberter M, Johansson J & Fisahn, A (2021) 
    Bri2 BRICHOS chaperone rescues impaired fast-spiking interneuron behavior and gamma oscillations in an AD mouse model in vitro.
    Neurobiology of Disease 159, 105514          

    AG Isla, H Balleza-Tapia & A Fisahn (2021)
    Efficacy of pharmacological interventions against degradation of cognition-relevant brain rhythms in animal models of Alzheimer´s Disease: A systematic review.
    Experimental Neurology 343, 113743.

    Andrade-Talavera Y*, Balleza-Tapia H*, Dolz-Gaiton P, Johansson J & Fisahn, A(* co-first author) (2021)
    Ablation of p75NTR-signaling strengthens gamma-theta rhythm interaction and counteracts Aβ-induced degradation of neuronal dynamics in mouse hippocampus in vitro. 
    Translational Psychiatry 11(1), 1-14.      

    Y Andrade-Talavera, L Arroyo-García, G Chen, J Johansson & A Fisahn (2020)
    Modulation of Kv3.1/Kv3.2 promotes gamma oscillations by rescuing Aβ-induced desynchronization of fast-spiking interneuron firing in an AD mouse model in vitro.
    J.Physiol. 598(17), 3711-3725.                

    G Chen, Y Andrade-Talavera, S Tambaro, , A Leppert, HE Nilsson, x Zhong, M Landreh, P Nilsson, H Herbert, H Biverstål, A Fisahn, A Abelein, & J Johansson (2020)
    Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro.
    Communications Biol. 3(1), 32-37.         

    Balleza-Tapia H, Dolz-Gaiton P, Andrade-Talavera Y & Fisahn, A. (2020)
    Capsaicin-induced impairment of functional network dynamics in mouse hippocampus via a TrpV1 receptor-independent pathway: putative involvement of Na+/K+-ATPase
    Molecular Neurobiology 57(2), 1170-1185.

    Björefeldt, A., Kurudenkandy, R., Zetterberg, H., Hanse, E. & Fisahn, A. (2020)
    Human cerebrospinal fluid promotes spontaneous gamma oscillations in the hippocampus in vitro.
    Hippocampus 30(2), 101-113.

    Balleza-Tapia H, Crux S, Andrade-Talavera Y, Dolz-Gaiton P, Papadia D, Chen G, Johansson J & Fisahn A (2018)
    TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Aβ-induced impairment in mouse hippocampus in vitro.
    elife 7

    G. Chen, A. Abelein, H.E. Nilsson, A. Leppert, Y. Andrade-Talavera, S. Tambaro, L. Hemmingsson, F.R. Kurudenkandy, M. Landreh, H. Biverstål, P.J.B Koeck, J. Presto, H. Hebert, A. Fisahn &J. Johansson (2017)
    Bri2 BRICHOS client specificity and chaperone activity are governed by assembly state
    Nature Communications 8, 2081.           

    M. S. Wyeth, K. A. Pelkey, X. Yuan, G. Vargish, A. Johnston, S. Hunt, C. Fang, D. Abebe, V. Mahadevan, A. Fisahn, M. W. Salter, R. R. McInnes, R. Chittajallu & Chris J. McBain (2017) 
    Neto auxiliary subunits regulate interneuron somatodendritic and presynaptic kainate receptors to control network inhibition
    Cell Reports 20, 2156-2168.

    Andersson, R., Galter, D., Papadia, D. & Fisahn, A. (2017)
    Histamine induces hippocampal gamma oscillations through H1R-mediated inhibition of KCNQ channels.
    Neuropharmacology 118, 13-25.

    Cohen, S., Presto, J., Arosio, P., Kurudenkandy, R., Bieverstål, H., Dolfe, L., Dunning, C., Frohm, B., Vendruscolo, M., Johansson, J., Dobson, C., Fisahn, A.*, Knowles, T.* & Linse, S.* (2015) (* co-senior authors)
    A molecular chaperone inhibits the toxicity of Aβ42 aggregates by supressing a single step in the reaction pathway.
    Nature Structural and Molecular Biology 22, 207-213.

    Lian, X., Bao, X., Zilberter, M., Westman, M., Fisahn, A., Chien, K.R. & Palecek, S.P. (2015)
    Chemically defined essential conditions for human cardiomyocytes differentiation from pluripotent stem cells
    Nature Methods 12, 595-596.                

    Full list of Publications

    Full list of publications from Google Scholar

    Visiting address

    Karolinska Institutet Campus Solna
    Bioclinicum
    Akademiska stråket 1
    J10:30
    17164 Stockholm

    External website

    External web site of the Fisahn Laboratory.