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Functional neuroanatomy of the cerebellum

Principal investigator: Dr. Tom Ruigrok

The cerebellum plays an important role in learning and coordination of movements. In addition, it is suggested to be involved in autonomic and cognitive processes. The uniform and crystalline structure of the cerebellar cortex indicates that the in and output organization of the cerebellar connections must be highly differentiated. Our group is involved in charting the the organizational principles of the input, throughput, and output of the cerebellum. In doing so, we continue the work of Prof. dr. Jan Voogd, former chairman of the Dept. of Anatomy, EURotterdam), who was among the first to recognize and elaborate the concept of the modular organization of cerebellar connections.

Presently, we are investigating if and if so, in what way, these modules may represent functional entities and concentrate on the intermediate cerebellar modules (C-modules). Questions which are tackled are:

  • How are the C-modules organized with respect to selective Purkinje cell markers such as Zebrin?
  • How are these modules connected with the brain stem and spinal cord?
  • What is the impact of these modules on ongoing motor behavior, in particular on the gain of peripheral reflexes triggered during ongoing locomotion?

Selected recent publications

  • Ruigrok TJ, Apps R. A light microscope-based double retrograde tracer strategy to chart central neuronal connections. Nat Protoc 2007;2(8):1869-78.

  • Apps R, Ruigrok TJ. A fluorescence-based double retrograde tracer strategy for charting central neuronal connections. Nat Protoc 2007;2(8):1862-8

  • Pijpers A, Ruigrok TJ. Organization of pontocerebellar projections to identified climbing fiber zones in the rat. J Comp Neurol 2006;496(4):513-28.

  • Pijpers A, Apps R, Pardoe J, Voogd J, Ruigrok TJ. Precise Spatial Relationships between Mossy Fibers and Climbing Fibers in Rat Cerebellar Cortical Zones. J Neurosci 2006;26(46):12067-12080.

  • Pijpers A. Functional anatomy of the intermediate cerebellum in the rat. Rotterdam: Erasmus MC Rotterdam; 2006.

  • Simpson JI, Hulscher HC, Sabel-Goedknegt E, Ruigrok TJ. Between in and out: linking morphology and physiology of cerebellar cortical interneurons. Prog Brain Res 2005;148:329-40.

  • Pijpers A, Voogd J, Ruigrok TJ. Topography of olivo-cortico-nuclear modules in the intermediate cerebellum of the rat. J Comp Neurol 2005;492(2):193-213.

  • Koekkoek SK, Yamaguchi K, Milojkovic BA, Dortland BR, Ruigrok TJ, Maex R, De Graaf W, Smit AE, Vanderwerf F, Bakker CE and others. Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X Syndrome. Neuron 2005;47(3):339-52.

  • Bronsing R, van der Burg J, Ruigrok TJ. Modulation of cutaneous reflexes in hindlimb muscles during locomotion in the freely walking rat: A model for studying cerebellar involvement in the adaptive control of reflexes during rhythmic movements. Prog Brain Res 2005;148:243-57.

  • Voogd J, Ruigrok TJ. The organization of the corticonuclear and olivocerebellar climbing fiber projections to the rat cerebellar vermis: the congruence of projection zones and the zebrin pattern. J Neurocytol 2004;33(1):5-21.

  • Ruigrok TJH. Precerebellar nuclei and red nucleus. In: Paxinos G, editor. The rat nervous system, third edition. San Diego: Elsevier Academic Press; 2004. p 167-204.

  • Voogd J, Pardoe J, Ruigrok TJ, Apps R. The distribution of climbing and mossy fiber collateral branches from the copula pyramidis and the paramedian lobule: congruence of climbing fiber cortical zones and the pattern of zebrin banding within the rat cerebellum. J Neurosci 2003;23(11):4645-56.

  • Ruigrok TJH. Bewegen: de rol van het cerebellum. Bewegingsstoornissen. 2003.

  • Ruigrok TJ. Collateralization of climbing and mossy fibers projecting to the nodulus and flocculus of the rat cerebellum. J Comp Neurol 2003;466(2):278-98.

  • Koekkoek SK, Hulscher HC, Dortland BR, Hensbroek RA, Elgersma Y, Ruigrok TJ, De Zeeuw CI. Cerebellar LTD and learning-dependent timing of conditioned eyelid responses. Science 2003;301(5640):1736-9.

  • De Zeeuw CI, Chorev E, Devor A, Manor Y, Van Der Giessen RS, De Jeu MT, Hoogenraad CC, Bijman J, Ruigrok TJ, French P and others. Deformation of network connectivity in the inferior olive of connexin 36-deficient mice is compensated by morphological and electrophysiological changes at the single neuron level. J Neurosci 2003;23(11):4700-11.

  • Bronsing R, van der Burg J, Ruigrok TJH. Step cycle dependent modulation of peripheral reflexes in rat during treadmil walking. In: Duysens J, Smits-Engelsman BCM, Kingma H, editors. Control of posture and gait. Nijmegen: Published by the International Society for  Postural and Gait Research; 2001. p 525-528.

  • Teune TM, van der Burg J, van der Moer J, Voogd J, Ruigrok TJH. Topography of cerebellar nuclear projections to the brain stem in the rat. In: Gerrits NM, Ruigrok TJH, De Zeeuw CI, editors. Cerebellar modules:  molecules, morphology and function. Volume 124, Progress in Brain Research. Amsterdam: Elsevier Science B.V.; 2000. p 141-172.

  • Ruigrok TJ, Voogd J. Organization of projections from the inferior olive to the cerebellar nuclei in the rat. J Comp Neurol 2000;426(2):209-28.

  • Teune TM, van der Burg J, Voogd J, Ruigrok TJH. Cerebellar collateralization to prerubral, rubral, pontine reticulotegmental and inferior olivary nuclei. A non-fluorescent double retrograde tracing study in the rat. J. Comp. Neurol. 1999;submitted.

  • Oldenbeuving AW, Eisenman LM, De Zeeuw CI, Ruigrok TH. Inferior olivary-induced expression of Fos-like immunoreactivity in the cerebellar nuclei of wild-type and Lurcher mice. Europ. J. Neurosci. 1999;11:3809-3822.

  • Toonen M, van Dijken H, Holstege JC, Ruigrok TJH, Koekkoek SKE, Hawkins RK, Teune TM, van der Burg J, De Zeeuw CI. Light microscopic and ultrastructural investigation of the dopaminergic innervation of the ventrolateral outgrowth of the rat inferior olive. Brain Res. 1998;802:267-273.

  • Teune TM, van der Burg J, De Zeeuw CI, Voogd J, Ruigrok TJH. Single Purkinje cell can innervate multiple classes of projection neurons in the cerebellar nuclei of the rat: a light microscopic and ultrastructural triple-tracer study in the rat. J.  Comp. Neurol. 1998;392:164-178.

  • De Zeeuw CI, Simpson JI, Hoogenraad CC, Galjart N, Koekkoek SKE, Ruigrok TJH. Microcircuitry and function of the inferior olive. Trends Neurosci. 1998;21:391-400.