Grillner Lab - Research

Our main aim is to understand the cellular bases of motor behaviour with a focus on the mechanisms underlying selection of behaviour and the neural bases of in particular locomotion.

Photo: Sten Grillner

This requires a detailed knowledge of which nerve cells take part, how they talk to each other through synaptic interaction and an understanding of the intrinsic function of these networks.

Essentially our research extends from ion channels and synapses to network mechanisms and behaviour utilising a multitude of techniques from patch clamp, tract tracing and cellular imaging to modelling and studies of behaviour. We utilise preferentially the lamprey as model organism.

We have been able to successfully model, based on detailed cellular knowledge, the networks responsible for the command and pattern generating systems for locomotion including steering and posture.

Our work continues with several foci including the role of the pallium/cortex, basal ganglia for selection of different patterns of motor behaviour, optic tectum for steering and eye motor coordination, the physiological role of different modulator systems acting through the spinal networks, and different ion channel subtypes contributing to neuronal function.

Our recent findings have shown that the lamprey forebrain has all components of the mammalian forebrain – a finding that has radically changed the view on the evolutionary origin of the vertebrate forebrain. The basic organisation had evolved 560 rather than 300 million years ago as previously believed.

The projects are supported by The Swedish Research Council, EU (Human Brain Project) and Karolinska Institutet.

Evolutionary conservation of the lamprey forebrain

Cortex/pallium is three-layered with the same efferent projection pattern to the brainstem-spinal cord as in mammals.

Cortex/pallium is three-layered with the same efferent projection pattern to the brainstem-spinal cord as in mammals
Photo: Sten Grillner

Suryanarayana SM, Robertson B, Wallén P, Grillner S (2017) Curr Biol 27:1-14.
Ocana F, Suryanarayana SM, Saitoh K, Kardamakis AA, Capantini L, Robertson B, Grillner S. (2015) Curr Biol 25:1-11.

Cortex/pallium has primary visual and somatosensory areas

Cortex/pallium has primary visual and somatosensory areas
Photo: Sten Grillner

The lamprey basal ganglia and the dopamine system is conserved

The organisation of the basal ganglia including the dopamine system is virtually identical throughout vertebrate phylogeny – from lamprey to primates. This applies to the overall neural organisation, transmitters, peptides, synaptic connectivity and expression of ion channels.

Photo: Sten Grillner

Grillner S and Robertson B. (2016) Curr Biol, 26: R1088-1100.
Stephenson-Jones M, Floros O, Robertson B, Grillner S (2012) Proc Natl Acad Sci U S A. 109:164-73.
Stephenson-Jones M, Samuelsson E, Ericsson J, Robertson B and Grillner S (2011) Curr. Biol. 21:1081-91.

The interaction between the forebrain and the optic tectum

The optic tectum contains motor circuits for the control of eye and orienting/evasive movements and receives visual input arranged in a retinotopic map. The optic tectum is controlled from both the basal ganglia and cortex/pallium. We have used an isolated eye-brain preparation to allow for a detailed analysis.

The interaction between the forebrain and the optic tectum
Photo: Sten Grillner

Pérez-Fernández J, Kardamakis AA, Suzuki DG, Robertson B, Grillner S. (2017) Neuron 96:1-15.
Kardamakis A, Pérez-Fernández J, Grillner S. (2016) ELife pii: e16472. doi: 10.7554/eLife.16472.
Kardamakis AA, Saitoh K. and Grillner S. (2015) Proc Natl Acad Sci USA E1956-65.

Modelling, the neural control of action

Locomotor network of the lamprey

Locomotor network of the lamprey. Left: Schematic representation of the forebrain, brainstem and spinal components of the neural circuitry generates rhythmic locomotor activity. Middle: Neuron model simulation using Hodgkin-Huxley formalism of the action potential with fast and slow afterhyperpolarisation (AHP) and synaptic properties. Right: Network model simulation of rhythmic, alternating activity in the spinal segmental network.

The mechanisms underlying the operation of the forebrain and midbrain in action selection are being investigated through detailed modelling based on experimental data, on the systems level as well as on the cellular and subcellular levels.

Grillner S, Cangiano L, Hu G, Thompson R, Hill R, Wallén P (2000) Brain Res 886:224-36.
Kozlov A, Huss M, Lansner A, Hellgren Kotaleski J, Grillner S (2009) Proc Natl Acad Sci USA 106:20027-32
Kozlov A, Kardamakis A, Hellgren Kotaleski J, Grillner S (2014) Proc Natl Acad Sci USA 111(9):3591-6
Suryanarayana SM, Hellgren Kotaleski J, Grillner S, Gurney KN. (2018) Roles for globus pallidus externa revealed in a computational model of action selection in the basal ganglia. Neural Networks, in press.
Lindroos R, Dorst MC, Du K, Filipović M, Keller D, Ketzef M, Kozlov AK, Kumar A, Lindahl M, Nair AG, Pérez-Fernández J, Grillner S, Silberberg G, Hellgren Kotaleski J. (2018) Front Neural Circuits 12:3. doi: 10.3389/fncir.2018.00003. eCollection.

The enigmatic cerebrospinal fluid-contacting neurons sense deviations from normal pH at the central canal and in hypothalamus

Photo: Sten Grillner

Jalalvand E, Robertson B, Tostivint H, Wallén P, Grillner S. (2018) J Neurosci. 38:7713-24.
Jalalvand E, Robertson B, Wallén P, Grillner S. (2016) Nature Commun 7:10002. doi: 10.1038/ncomms10002.

Both spinal and hypothalamic cerebrospinal fluid-contacting (CSF-c) neurons serve as pH sensors, thereby providing a novel homeostatic module for the regulation of pH in the CNS. In the spinal cord, acidic pH is mediated by the ASIC3 and alkaline pH via PKD2L1 channels, whereas in hypothalamus the acidic response is mediated via ASIC3 and alkaline pH via connexin hemichannels.