Neuroscience

Current projects

Nucleo-olivary inhibition
This project concerns the function of the projection from the deep nuclei of the cerebellum to the inferior olive. It was shown with direct stimulation of the nucleo-olivary fibres (Hesslow 1986) and by indirect methods in collaboration with Gert Andersson and Martin Garwicz (Andersson &Hesslow, 1987; Andersson, Garwicz & Hesslow, 1988) that this pathway is inhibitory and GABA-ergic. Nelson, Barmack and Mugnaini showed that the neurones contain GABA. We suggested that the cerebellar inhibition of the olive is a negative feed-back mechanism, controlling both synapse-specific cerebellar plasticity and general excitability of Purkinje and deep nuclear cells. The first assumption was tested and confirmed by Hesslow & Ivarsson (1996) and Fredrik Bengtsson (2004) and the second assumption  was confirmed by Fredrik Bengtsson (2006). He has shown that blocking the nucleo-olivary pathway causes an increase in climbing fibre acitivity that is sufficient to silence spontaneous activity in Purkinje cells. Anders Rasmussen, Riccardo Zucca and Pär Svensson are currently working on more subtle aspects of this control system.

 

Classical conditioning in cerebellar neurones
The third body of work, mainly done together with Magnus Ivarsson and Pär Svensson, has addressed the role of the cerebellum in classical conditioning. Hesslow (1994a,b) and (Ivarsson, Svensson & Hesslow, 1997) showed the role of several microzones in the cerebellar cortex in bilateral control of conditioned eye-blink responses. Hesslow & Ivarsson (1996) supported the hypothesis that conditioned responses via nucleo-olivary inhibition provides a negative feed-back signal to the inferior olive. Recordings from Purkinje cells (Hesslow & Ivarsson,1994) support the cerebellar model of classical conditioning (Yeo and Hesslow, 1998). The most recent work has concerned the role of the mossy fibre system as a pathway for the conditioned stimulus information to the cerebellum (Svensson, Ivarsson and Hesslow, 1997; Hesslow, Svensson andIvarsson, 1999).
Classical conditioning (popular account)

Classical conditioning in humans
We are currently pursuing a project for studying human eyeblink conditioning. We are using a setup developed in Chris de Zeeuw’s lab in Rotterdam by Bas Koekkokk, Henk-Jan Boele and Jan-Willem Potters for training humans with tone and airpuffs. Blinks are monitored by measuring changes in the magnetic field generated by a small magnet fastened on the eyelid. The PhD student Karolina Löwgren is using the setup for studying children with speech and language disabilities. The working hypothesis is that the underlying problem for some of these children is a cerebellar dysfunction.

Internal simulation of behaviour and perception
This is a theoretical project concerning possible brain mechanisms for generating the inner world of consciousness and thinking. Hesslow (1994c, 2002) (and some papers listed under Philosophy) suggest that the inner world arises as a consequence of the brain’s ability to generate its own input. A ’simulation’ theory  of cognitive function is developed. It is based on three core hypotheses about brain function. First, it is assumed that behaviour can be simulated by activating motor structures as during an overt action, but suppressing its execution. The second assumption is that perception can be simulated by internal activation of sensory cortex as during normal perception of external stimuli. Third, it is assumed that both overt and covert actions can elicit perceptual simulation of their normal consequences. A large body of evidence supports these assumptions. It is argued that the simulation mechanism can explain many of the traditional problems concerning consciousness and the inner world. The basic idea has now been implemented in robot simulations by Dan-Anders JirenhedMagnus Johnsson and Tom Ziemke.

Research group

 

The group descends from the research group headed by Olov Oscarsson who was a PhD student of Anders Lundberg and later worked under J.C. Eccles in Australia. Oscarsson studied the spinal pathways to the cerebellum and his main contributions were the discoveries of the zonaland microzonal organisation of the cerebellar cortex. G. Hesslow, who was a PhD student of Oscarsson, started working on the physiology of the cerebellar climbing fibre system under the guidance of Gert Andersson and Carl-Fredrik Ekerot. Hesslow’s main interest was behaviour and he studied classical conditioning in Christopher Yeo’s lab at University College, London. He then set up a new laboratory in Oscarsson’s old department and now works on the cerebellar mechanisms of classical conditioning with his  students Fredrik Bengtsson, Dan-Anders Jirenhedand Magnus Larsson.

 

The research is mainly funded by The Swedish Medical Research Council, Åhlenstiftelsen, Gyllenstierna-Krapperupstifelsen.

 

Members of the research group:
Germund Hesslow, Professor
Magnus Ivarsson, PhD 1998. Currently at Merck, Sharpe and Dome, GB
Pär Svensson, PhD 2000. (Currently at SIDA, Stockholm)  
Fredrik Bengtsson, PhD 2005
Dan-Anders Jirenhed , PhD 2007Fredrik Johansson, PhD studentKarolina Löwgren, PhD student
Anders Rasmussen, PhD studentRiccardo Zucca, PhD student (Currently at Pompeu Fabra University in Barcelona)
Kersti Larsson, laboratory technician

Pär Svensson Fredrik Bengtsson Kersti Larsson Germund Hesslow Dan-AndersJirenhed Anders Rasmussen

Selected publications

Campbel NC, Hesslow G (1986a), The secondary spikes of climbing fibre responses recorded from Purkinje cell somata in the cat cerebellum. Journal of Physiology 377: 207-224.  PDF
Campbel NC, Hesslow G (1986b), The secondary spikes of climbing fibre responses recorded from Purkinje cell axons in the cat cerebellum. Journal of Physiology 377: 225-235.  PDF
Hesslow G (1986), Inhibition of inferior olivary transmission by mesencephalic stimulation in the cat, Neurosci Lett 63:76-80.  PDF
Andersson G, Hesslow G (1987), Inferior olive excitability after high frequency climbing fibre activation in the cat, Experimental Brain Research 67:523-532.  PDF
Andersson G, Garwicz M, Hesslow G (1988), Evidence for GABA-mediated cerebellar inhibition of the inferior olive in the cat, Experimental Brain Research 72:450-456.  PDF
Hesslow G. (1994a) Correspondence between climbing fibre input and motor output in eyeblink related areas in cat cerebellar cortex. J Physiol 476:229-244.  PDF
Hesslow G (1994b). Inhibition of conditioned eye-blink responses by stimulation of the cerebellar cortex in the cat.  J Physiol 476:245-256 .  PDF
Hesslow, G. (1994c) Will neuroscience explain consciousness? Journal of Theoretical Biology . 171:29-39  PDF
Hesslow G. (1995). Classical conditioning of eyeblink in decerebrate cats and ferrets. In Ferrell and Proske (ed.) Neural Control of Movement. Plenum Press. pp 117-122.  PDF
Hesslow G, Ivarsson M (1994). Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. Neuroreport 5:649-652.  PDF
Hesslow G, Ivarsson M (1996). Inhibition of the inferior olive during conditioned responses in the decerebrate ferret. Exp Brain Res, 10:36-46.  PDF
Svensson P, Ivarsson M and Hesslow G (1997). Effect of Varying the Intensity and Train Frequency of Forelimb and Cerebellar Mossy Fiber Conditioned Stimuli on the Latency of Conditioned Eye-Blink Responses in Decerebrate Ferrets. Learning &Memory, 4: 105-115. PDF
Ivarsson M, Svensson P and Hesslow G (1997). Bilateral disruption of conditioned responses after unilateral blockade of cerebellar output in the decerebrate ferret. J Physiol , 502: 189-201. Link
Yeo CH and Hesslow G (1998). Cerebellum and conditioned reflexes. Trends in Cognitive Sciences ,  2: 322-330. PDF
Hesslow G, Svensson P and Ivarsson M (1999). Learned Movements Elicited by Direct Stimulation of Cerebellar Mossy Fiber Afferents. Neuron, 24: 179-185. PDF
Hesslow, G. (2001) Medvetande som simulering av beteende och perception. I H. Lagercrantz (red) Hjärnan och medvetandet. Nya Doxa, Nora HTML
Hesslow, G (2001) Lost in thought. Review of Rodolfo Llinás book I of the Vortex: From Neurons to Self HTML
Hesslow, G. (2001) New lecture on consciousness. Powerpoint presentation. PP
Hesslow, G. (2002) Thinking as Simulation of Behaviour: an Associationist View of Cognitive Function HTML
Hesslow, G. and Yeo, C.H. (2002) The Functional Anatomy of Skeletal Conditioning. In Moore, J.W. (ed) A Neuroscientist’s Guide to Classical Conditioning. Springer, New York Link
Hesslow, G. (2002) Conscious thought as simulation of behaviour and perception. Trends in Cognitive Sciences, 6:242-247 PDF
Bengtsson, F., Svensson, P and Hesslow, G. (2004) Feedback control of Purkinje cell activity by the cerebello-olivary pathway. European Journal of Neuroscience 20: 2999–3005 PDF
Svensson, P, Bengtsson, F and Hesslow, G  (2006) Cerebellar inhibition of inferior olivary transmission in the decerebrate ferret. Experimental Brain Research 168: 241-53 PDF
Bengtsson F & Hesslow G (2006). Cerebellar Control of the Inferior Olive. Cerebellum 5: 7-14. PDF
Jirenhed D-A, Bengtsson F, & Hesslow G (2007). Acquisition, Extinction, and Reacquisition of a Cerebellar Cortical Memory Trace. J Neurosci 27: 2493-2502 PDF
Bengtsson F, Jirenhed D-A, Svensson P & Hesslow G (2007). Extinction of conditioned blink responses by cerebello-olivary pathway stimulation.  NeuroReport 18: 1479-82 Link
Hesslow, G. (2007)  Hjärnan och medvetandet.  Hjärnan. K. Österberg (red.), Karolinska University Press, Stockholm. See under Philosophy
Rasmussen, A, Jirenhed, D.-A, Hesslow, G. (2008). Simple and Complex Spike Firing Patterns in Purkinje cells During Classical Conditioning. Cerebelllum. 7:563-566 Link
Svensson P, Jirenhed DA, Bengtsson F, Hesslow G (2010) Effect of Conditioned Stimulus Parameters on Timing of Conditioned Purkinje Cell Responses. Journal of Neurophysiology 103:1329-1336. PDF
Jirenhed D-A, Hesslow G (2011) Learning Stimulus Intervals – Adaptive Timing of Conditioned Purkinje Cell Responses. Cerebellum 10: 523-535 Link
Jirenhed D-A, Hesslow G (2011) Time Course of Classically Conditioned Purkinje Cell Response is Determined by Initial Part of Conditioned Stimulus. Journal of Neuroscience. 31: 9070 –9074 Link
Johnsson, M., Martinsson, M., Gil, D. and Hesslow, G. (2011). Associative Self-Organizing Map. In Mwasiagi, J.I. (Ed), Self Organising Maps – Applications and Novel Algorithm Design, INTECH, 603-626. ISBN: 978-953-307-546-4
Johnsson, M., Gil, D., Hesslow, G. and Balkenius C. (2011). Internal Simulation in a Bimodal System. Scandinavian Conference on Artificial Intelligence (SCAI 2011), Norwegian University of Science and Technology, Trondheim, Norway.
Bengtsson,F. and Hesslow,G. (2012). Feedback control in the olivo-cerebellar loop. In Manto M, Gruol D, Schmahmann J, Koibuchi N and Rossi F. (eds), The Handbook of the Cerebellum and Cerebellar Disorders. Springer.
Hesslow,G. (2012) Current status of the simulation theory of cognition. Brain Research 1428:71-79. Link