Structural Basis of Cerebellar Microcircuits in the Rat

The topography of the cerebellar cortex is described by at least three different maps, with the basic units of each map termed “microzones,” “patches,” and “bands.” These are defined, respectively, by different patterns of climbing fiber input, mossy fiber input, and Purkinje cell (PC) phenotype. Based on embryological development, the “one-map” hypothesis proposes that the basic units of each map align in the adult animal and the aim of the present study was to test this possibility. In barbiturate anesthetized adult rats, nanoinjections of bidirectional tracer (Retrobeads and biotinylated dextran amine) were made into somatotopically identified regions within the hindlimb C1 zone in copula pyramidis. Injection sites were mapped relative to PC bands defined by the molecular marker zebrin II and were correlated with the pattern of retrograde cell labeling within the inferior olive and in the basilar pontine nuclei to determine connectivity of microzones and patches, respectively, and also with the distributions of biotinylated dextran amine-labeled PC terminals in the cerebellar nuclei. Zebrin bands were found to be related to both climbing fiber and mossy fiber inputs and also to cortical representation of different parts of the ipsilateral hindpaw, indicating a precise spatial organization within cerebellar microcircuitry. This precise connectivity extends to PC terminal fields in the cerebellar nuclei and olivonuclear projections. These findings strongly support the one-map hypothesis and suggest that, at the microcircuit level of resolution, the cerebellar cortex has a common plan of spatial organization for major inputs, outputs, and PC phenotype.

[1]  T. Ruigrok.  Ins and Outs of Cerebellar Modules , 2010, The Cerebellum.

[2]  Germund Hesslow,et al.  Cerebellum and conditioned reflexes , 1998, Trends in Cognitive Sciences.

[3]  C. Buisseret-Delmas,et al.  The cerebellar olivo-corticonuclear connections in the rat , 1993, Progress in Neurobiology.

[4]  R. Parenti,et al.  Multiple zonal projections of the basilar pontine nuclei to the cerebellar cortex of the rat , 2001, The Journal of comparative neurology.

[5]  Richard Apps,et al.  Cerebellar cortical organization: a one-map hypothesis , 2009, Nature Reviews Neuroscience.

[6]  Richard Apps,et al.  Precise Spatial Relationships between Mossy Fibers and Climbing Fibers in Rat Cerebellar Cortical Zones , 2006, The Journal of Neuroscience.

[7]  J. W. Lighthall,et al.  An HRP and autoradiographic study of the projection from the cerebellar cortex to the nucleus interpositus anterior and nucleus interpositus posterior of the cat , 1979, The Journal of comparative neurology.

[8]  R. Hawkes,et al.  Parasagittal organization of the rat cerebellar cortex: Direct comparison of purkinje cell compartments and the organization of the spinocerebellar projection , 1990, The Journal of comparative neurology.

[9]  C. Jahr,et al.  Patterned expression of Purkinje cell glutamate transporters controls synaptic plasticity , 2005, Nature Neuroscience.

[10]  Gang Chen,et al.  Cerebellar Cortical Molecular Layer Inhibition Is Organized in Parasagittal Zones , 2006, The Journal of Neuroscience.

[11]  Y Shinoda,et al.  Projection patterns of single mossy fibers originating from the lateral reticular nucleus in the rat cerebellar cortex and nuclei , 1999, The Journal of comparative neurology.

[12]  D. Armstrong,et al.  Zonal organization of cortico-nuclear and nucleo-cortical projections of the paramedian lobule of the cat cerebellum. 2. The C2 zone , 1998, Experimental Brain Research.

[13]  Richard Apps,et al.  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 , 2003, The Journal of Neuroscience.

[14]  C. Buisseret-Delmas,et al.  Sagittal organization of the olivocerebellonuclear pathway in the rat. I. Connections with the nucleus fastigii and the nucleus vestibularis lateralis , 1988, Neuroscience Research.

[15]  N. Ramnani.  The primate cortico-cerebellar system: anatomy and function , 2006, Nature Reviews Neuroscience.

[16]  E. Dietrichs,et al.  The cerebellar corticonuclear and nucleocortical projections in the cat as studied with anterograde and retrograde transport of horseradish peroxidase , 2004, Anatomy and Embryology.

[17]  O. Larsell,et al.  The morphogenesis and adult pattern of the lobules and fissures of the cerebellum of the white rat , 1952, The Journal of comparative neurology.

[18]  R. Hawkes,et al.  Pattern formation in the cerebellar cortex. , 2000, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[19]  Trygve B. Leergaard,et al.  Topographical organization in the early postnatal projection: A carbocyanine dye and 3‐D computer reconstruction study in the rat , 1995 .

[20]  C. Schwarz,et al.  Spatial arrangement of cerebro‐pontine terminals , 2001, The Journal of comparative neurology.

[21]  Tahl Holtzman,et al.  Electrophysiological Localization of Eyeblink-Related Microzones in Rabbit Cerebellar Cortex , 2010, The Journal of Neuroscience.

[22]  Martin Garwicz,et al.  Spread of synaptic activity along parallel fibres in cat cerebellar anterior lobe , 2004, Experimental Brain Research.

[23]  Richard Apps,et al.  Somatotopical organisation within the climbing fibre projection to the paramedian lobule and copula pyramidis of the rat cerebellum , 1997, The Journal of comparative neurology.

[24]  Jan Voogd,et al.  Cerebellum and Precerebellar Nuclei , 2012 .

[25]  J G Bjaalie,et al.  Topographical organization in the early postnatal corticopontine projection: a carbocyanine dye and 3-D computer reconstruction study in the rat. , 1995, The Journal of comparative neurology.

[26]  Martin Paukert,et al.  Zones of Enhanced Glutamate Release from Climbing Fibers in the Mammalian Cerebellum , 2010, The Journal of Neuroscience.

[27]  J. Voogd,et al.  Connections of the Lateral Reticular Nucleus to the Lateral Vestibular Nucleus in the Rat. An Anterograde Tracing Study with Phaseolus vulgaris Leucoagglutinin , 1995, The European journal of neuroscience.

[28]  Masahiko Watanabe,et al.  Complementary stripes of phospholipase Cβ3 and Cβ4 expression by Purkinje cell subsets in the mouse cerebellum , 2006 .

[29]  J G Bjaalie,et al.  Salient anatomic features of the cortico-ponto-cerebellar pathway. , 1997, Progress in brain research.

[30]  Masahiko Watanabe,et al.  Complementary stripes of phospholipase Cbeta3 and Cbeta4 expression by Purkinje cell subsets in the mouse cerebellum. , 2006, The Journal of comparative neurology.

[31]  M. Garwicz,et al.  Anatomical and physiological foundations of cerebellar information processing , 2005, Nature Reviews Neuroscience.

[32]  T. Ruigrok,et al.  Selective Impairment of the Cerebellar C1 Module Involved in Rat Hind Limb Control Reduces Step-Dependent Modulation of Cutaneous Reflexes , 2008, The Journal of Neuroscience.

[33]  Douglas R Wylie,et al.  Organization of the cerebellum: Correlating zebrin immunochemistry with optic flow zones in the pigeon flocculus , 2011, Visual Neuroscience.

[34]  J. Courville,et al.  Cerebellar corticonuclear projection in the cat. The paramedian lobule. An experimental study with silver methods. , 1973, Brain research.

[35]  I. Sugihara,et al.  Projection patterns of single mossy fiber axons originating from the dorsal column nuclei mapped on the aldolase C compartments in the rat cerebellar cortex , 2011, The Journal of comparative neurology.

[36]  Henrik Jörntell,et al.  Organizational Principles of Cerebellar Neuronal Circuitry. , 1998, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[37]  N. Barmack,et al.  Distribution of granule cells projecting to focal Purkinje cells in mouse uvula-nodulus , 2008, Neuroscience.

[38]  E. Dietrichs.  The cerebellar corticonuclear and nucleocortical projections in the cat as studied with anterograde and retrograde transport of horseradish peroxidase , 1981, Experimental Brain Research.

[39]  P. Brodal,et al.  The pontine projection to the cerebellar anterior lobe. An experimental study in the cat with retrograde transport of horseradish peroxidase , 1977, Experimental Brain Research.

[40]  J. Rawson,et al.  Morphology of parallel fibres in the cerebellar cortex of the rat: An experimental light and electron microscopic study with biocytin , 1994, The Journal of comparative neurology.

[41]  R. Parenti,et al.  The basilar pontine nuclei and the nucleus reticularis tegmenti pontis subserve distinct cerebrocerebellar pathways. , 2005, Progress in brain research.

[42]  Yoshikazu Shinoda,et al.  Molecular, Topographic, and Functional Organization of the Cerebellar Nuclei: Analysis by Three-Dimensional Mapping of the Olivonuclear Projection and Aldolase C Labeling , 2007, The Journal of Neuroscience.

[43]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[44]  Richard Apps,et al.  Columnar organisation of the inferior olive projection to the posterior lobe of the rat cerebellum , 1990, The Journal of comparative neurology.

[45]  P. Buisseret,et al.  The X zone and CX subzone of the cerebellum in the rat , 1993, Neuroscience Research.

[46]  Y. Shinoda,et al.  Molecular, Topographic, and Functional Organization of the Cerebellar Cortex: A Study with Combined Aldolase C and Olivocerebellar Labeling , 2004, The Journal of Neuroscience.

[47]  D. Armstrong,et al.  Investigations of the Olivocerebellar and Spino-Olivary Pathways , 1982 .

[48]  Peter Thier,et al.  Binding of signals relevant for action: towards a hypothesis of the functional role of the pontine nuclei , 1999, Trends in Neurosciences.

[49]  I. Sugihara,et al.  Projection of reconstructed single purkinje cell axons in relation to the cortical and nuclear aldolase C compartments of the rat cerebellum , 2009, The Journal of comparative neurology.

[50]  Peri- and Postnatal Development of Cerebellar Compartments in the Mouse , 2013, The Cerebellum.

[51]  M. Garwicz,et al.  Micro‐Organization of Olivocerebellar and Corticonuclear Connections of the Paravermal Cerebellum in the Cat , 1996, The European journal of neuroscience.

[52]  Y Yarom,et al.  Patches of synchronized activity in the cerebellar cortex evoked by mossy-fiber stimulation: questioning the role of parallel fibers. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Richard Apps,et al.  Pontine and lateral reticular projections to the c1 zone in lobulus simplex and paramedian lobule of the rat cerebellar cortex , 2002, The Cerebellum.

[54]  Per Brodal,et al.  Lamellar Organization of Pontocerebellar Neuronal Populations. A Multi‐tracer and 3‐D Computer Reconstruction Study in the Cat , 1994, The European journal of neuroscience.

[55]  I. Sugihara,et al.  Clustered Fine Compartmentalization of the Mouse Embryonic Cerebellar Cortex and Its Rearrangement into the Postnatal Striped Configuration , 2012, The Journal of Neuroscience.

[56]  G. M. Shambes,et al.  Fractured somatotopy in granule cell tactile areas of rat cerebellar hemispheres revealed by micromapping. , 1978, Brain, behavior and evolution.

[57]  H. Yaginuma,et al.  Somatotopic termination of the spino-olivary fibers in the cat, studied with the wheat germ agglutinin-horseradish peroxidase technique , 2004, Experimental Brain Research.

[58]  D. Armstrong,et al.  Zonal organization of cortico-nuclear and nucleo-cortical projections of the paramedian lobule of the cat cerebellum. 1. The C1 zone , 1998, Experimental Brain Research.

[59]  I. Sugihara.  Compartmentalization of the Deep Cerebellar Nuclei Based on Afferent Projections and Aldolase C Expression , 2011, The Cerebellum.

[60]  R. Hawkes,et al.  Zebrin II: A polypeptide antigen expressed selectively by purkinje cells reveals compartments in rat and fish cerebellum , 1990, The Journal of comparative neurology.

[61]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[62]  R. Harvey,et al.  Quantitatives studies on the mammalian cerebellum , 1991, Progress in Neurobiology.

[63]  Douglas R Wylie,et al.  Zebrin-Immunopositive and -Immunonegative Stripe Pairs Represent Functional Units in the Pigeon Vestibulocerebellum , 2012, The Journal of Neuroscience.

[64]  J. Bower,et al.  Congruence of spatial organization of tactile projections to granule cell and Purkinje cell layers of cerebellar hemispheres of the albino rat: vertical organization of cerebellar cortex. , 1983, Journal of neurophysiology.