About the project
Our work is fundamentally motivated and guided by a long-term interest in the brain’s most unique property: its ability to generate conscious experience. Thus, we primarily study multilevel electrical and chemical neuronal signaling at time scales of milliseconds to seconds – the type of processes likely to be involved in consciousness
We study neurophysiology of the mammalian brain, in particular the cerebral cortex including the hippocampal formation, at three main levels, using a at three main levels, using a variety of electrophysiological, optical, and computational methods:
- Single neuron signaling, computation, and neuromodulation
- Functions, dynamics and neuromodulation of neural circuits
- Consciousness research in humans and animals: TMS-EEG experiments
In this research, we also use opportunities to contribute to related areas, including translational medicine - often in fruitful collaborations with experts in these fields. We believe that solid basic research often becomes useful in multiple ways, since functions and disorders are intimately connected
Challenges
In summary, we study neurophysiology of the mammalian brain, in particular the cerebral cortex including the hippocampal formation, at three main levels:
Single neuron signaling and computation
Since neurons are the main functional units of the brain, it is essential to understand how they encode and process information (“single neuron computation”). Using cellular electrophysiology (patch clamp etc.) and optical methods (confocal and 2-photon microscopy) in vitro and in vivo, combined with genetic engineering (transgenic mice, viral vectors, optogenetics), we study electrical and chemical signaling within and between neurons.
For example, we have discovered new mechanisms of action potential generation, after-potentials, regulation of spike frequency/ patterns and transmitter release, resonant filtering and signal processing by dendrites, axons and presynaptic terminals.
To enable these studies, we have introduced several advanced electrophysiological, optical, and computational methods to Scandinavia. In addition, we develop realistic computational models that we use for simulations and predictions in conjunction with experiments.
Functions, dynamics and neuromodulation of neural circuits
This is a relatively new line of research in our lab. The first studies are about to be published; others are at the planning stage. Briefly, by combining computational experiments in vitro and in vivo with modelling, we study how intrinsic properties and neuromodulation in single neurons and synapses influence the dynamics and functions of neural circuits in the cerebral cortex and hippocampus.
Consciousness research in humans and animals: TMS-EEG experiments
This is another new direction in our lab. Practical preparations started in 2014, and experiments in humans will begin in the spring and summer of 2015.
For decades our work has been motivated by a long-term interest in the brain’s ability to generate conscious experience.
However, until recently it was difficult to find methods and funding for studying consciousness experimentally. In 2014, however, we obtained funding for equipment for navigated transcranial magnetic stimulation (nTMS) combined with high density electroencephalography (hdEEG).
In 2015, we will start using nTMS-hdEEG for consciousness research in humans and animals. In particular, we will use this method for measuring a promising index of consciousness (the perturbational complexity index, PCI) developed by the groups of Giulio Tononi and Marcello Massimini.
Working in collaboration with researchers at Oslo University Hospital (Dr. P.G. Larsson and others) and Tononi’s group (Madison, Wisconsin, USA), we will measure PCI under a variety of conditions for testing theories of consciousness, and for assessing the validity of this and other indices and correlates of consciousness.
Basic research vs. translational medicine
While primarily doing basic research on brain signaling, we also use opportunities to contribute to related areas: ion channel functions, neuromodulation, synaptic transmission and plasticity, circuit dynamics, systems and cognitive neuroscience, including learning, memory and spatial navigation, brain development, neuropharmacology, neuroprotection against ischemic stroke and hypoxia, epilepsy research, and other areas of translational medicine - often in fruitful collaborations with experts in these fields.
For example, our finding that action potentials in the mammalian brain are often repolarized by both calcium- and voltage-gated potassium channels, has later been confirmed for many brain areas, and proved relevant for brain disorders in humans, including epilepsy, and neuroprotection against ischemic stroke and hypoxia.
Also our finding that M-type potassium channels make neurons particularly sensitive to input at certain frequencies (we call it “M-resonance”), along with their general control of excitability, have proved relevant for learning, memory and spatial navigation, as well as hereditary forms of epilepsy.
Thus, we and others found that transgenic suppression of M-channels caused severe memory deficits and epilepsy in mice, and others found that mutations in M-channel genes (KCNQ2-3) cause epilepsy in children.
These two examples illustrate that potassium channels, the most diverse class of ion channels generating the brain’s electrical signals, are valuable “molecular handles” for probing brain mechanisms at different levels.
In general, we believe that solid basic research inevitably becomes useful in multiple ways, because functions and disorders are intimately connected.