Laboratory of Molecular Neurophysiology and Plasticity


The main focus of our research is molecular neurophysiology in the hippocampus of rodents. Hippocampus is a key structure of the brain involved in learning and memory, which is especially suited for laboratory analyses of the molecular mechanisms underlying brain processes. A thorough characterization of the functional properties of the synapses in the mammalian brain is fundamental for our understanding of the healthy as well as the diseased brain. Ultimately our studies may help future patients suffering from brain-related disorders.

Research interests

A main ongoing project focuses on a transgenic mouse model where a synaptic protein (SorCS3) has been genetically removed (Breiderhoff et al., 2013, PLoS ONE). So far the exact function of the receptor is unknown, but others have proved strong expression in the hippocampal area Consequently we take advantage of field recordings in the CA1 and dentate gyrus of acutely isolated brain sections. Genetic evidence associates the SORCS3 gene to brain disorders. We have identified key roles of SorCS3 in synaptic plasticity, which point at essential functions for the receptor in learning and memory. A recent publication from our lab demonstrates impaired synaptic transmission and altered response during repeated synaptic activity (Christiansen et al., 2017, Hippocampus). In summary, our data indicate a key role of this sorting receptor in controlling glutamate receptor functionality. Now the aim is to pin-point the function in greater details, to further understand the genetic association to brain disorders.

Another line of studies aims to understand the underlying pathological mechanisms in the brain of a mouse model of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS). This model, the wobbler mouse, was genetically characterized by Dr. Thomas Schmitt-John and co-workers in 2005 (Nature Genetics). Here we employ electrophysiological analyses in the hippocampus to identify neurophysiological changes at different stages of disease progression in the brain of this mouse model. Interestingly, our data point at hippocampal hyperexcitability which is most pronounced in the brain of the symptomatic animals (Thielsen et al., 2013, PLoS ONE). Our laboratory recently substantiated excitatory-inhibitory imbalance in the brain of this model, by taking advantage of the GABAergic modulator diazepam and the ALS-drug riluzole (Andreasen et al., 2017, Neuroscience Letters).

A third current project involves analyses of positive allosteric modulators of the AMPA receptors, a subgroup of the glutamate receptors. AMPA receptors are key players in synaptic plasticity and their open state is stabilized in the presence of positive allosteric modulators. This interaction results in a strengthening of the synaptic transmission and a lowering of the induction threshold together with increased magnitude of the long-term potentiation (LTP). In more complex systems, the molecules improve learning and memory and increase BDNF expression associated with a range of positive effects on the brain. Evidence from the literature suggests possible roles as future therapeutic agents in brain disorders. We take advantage of the compounds as pharmacological tools in our studies of synaptic plasticity in the hippocampus of rodent brain slices. Recently we completed a detailed analysis of a novel allosteric modulator with an interesting dualistic profile (Christiansen et al., 2015, Neuroscience). These data will strengthen our knowledge of the modulators and facilitate future applications of the compounds as manipulators of synaptic plasticity in the human brain. Ongoing initiatives in the laboratory employ positive allosteric modulators with the aim of improving the synaptic impairments observed in the SorCS3 deficient mouse model.    


  • Brain slice electrophysiology in the hippocampus
  • Extracellular field recordings
  • Long-term depression (LTD) and long-term potentiation (LTP)
  • Patch-clamp electrophysiology
  • Immunohistochemical techniques
  • PCR-based genotyping

Collaborators and centres

  • Victoria García-Morales and Bernardo Moreno-López, University of Cádiz, Spain
  • Ulrik Bølcho and Anders Nykjær, DANDRITE, Department of Biomedicine, AU
  • Jan Egebjerg Jensen, Science and Technology, AU
  • Morten Skovgaard Jensen, Department of Biomedicine, AU
  • Jette Sandholm Kastrup, Dept. of Drug Design and Pharmacology, University of Copenhagen
  • Claire Francesca Meehan, Department of Neuroscience, University of Copenhagen
  • Thomas Schmitt-John, Science and Technology, AU
  • Karin Lykke-Hartmann, AU
  • Lasse K. Bak, Dept. of Drug Design and Pharmacology, University of Copenhagen
  • Rafael Fernández-Chacón, Sevilla, Spain

Research group members

The laboratory includes a number of Danish and international students in addition to a lab technician. We also regularly welcome Erasmus students.

Group leader

Mai Marie Holm

Associate professor


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