Cerebellar Cortical Molecular Layer Inhibition Is Organized in Parasagittal Zones

Molecular layer inhibitory interneurons generate on-beam and off-beam inhibition in the cerebellar cortex that is hypothesized to control the timing and/or spatial patterning of Purkinje cell discharge. On- and off-beam inhibition has been assumed to be spatially uniform and continuous within a folium. Using flavoprotein autofluorescence optical imaging in the mouse cerebellar cortex in vivo, this study demonstrates that the inhibition evoked by parallel fiber and peripheral stimulation results in parasagittal bands of decreases in fluorescence that correspond to zebrin II-positive bands. The parasagittal bands of decreased fluorescence are abolished by GABAA antagonists and reflect the activity of molecular layer interneurons on their targets. The same banding pattern was observed using Ca2+ imaging. The bands produce spatially specific decreases in the responses to peripheral input. Therefore, molecular layer inhibition is compartmentalized into zebrin II parasagittal domains that differentially modulate the spatial pattern of cerebellar cortical activity.

[1]  R. Hawkes,et al.  Whole-mount Immunohistochemistry: A High-throughput Screen for Patterning Defects in the Mouse Cerebellum , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  S. Budd,et al.  A Reevaluation of the Role of Mitochondria in Neuronal Ca2+ Homeostasis , 1996, Journal of neurochemistry.

[3]  R. Nudo,et al.  Stimulation‐induced [14C]2‐deoxyglucose labeling of synaptic activity in the central auditory system , 1986, The Journal of comparative neurology.

[4]  Y. Yarom,et al.  Cerebellar on-beam and lateral inhibition: two functionally distinct circuits. , 2000, Journal of neurophysiology.

[5]  R. Albin,et al.  Pharmacology, distribution, cellular localization, and development of GABAB binding in rodent cerebellum , 1993, Neuroscience.

[6]  M. Häusser,et al.  Tonic Synaptic Inhibition Modulates Neuronal Output Pattern and Spatiotemporal Synaptic Integration , 1997, Neuron.

[7]  B CHANCE,et al.  THE ENERGY-LINKED REACTION OF CALCIUM WITH MITOCHONDRIA. , 1965, The Journal of biological chemistry.

[8]  M. Finel,et al.  Diphenyleneiodonium inhibits reduction of iron-sulfur clusters in the mitochondrial NADH-ubiquinone oxidoreductase (Complex I). , 1994, The Journal of biological chemistry.

[9]  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.

[10]  B. Barbour Synaptic currents evoked in purkinje cells by stimulating individual granule cells , 1993, Neuron.

[11]  M. Häusser,et al.  Initiation and spread of sodium action potentials in cerebellar purkinje cells , 1994, Neuron.

[12]  David Willshaw,et al.  The cerebellum as a neuronal machine , 1999 .

[13]  Matsuo Matsushita,et al.  Spinocerebellar projections from the cervical enlargement in the cat, as studied by anterograde transport of wheat germ agglutinin–horseradish peroxidase , 1987, The Journal of comparative neurology.

[14]  R. Hawkes,et al.  Topography of purkinje cell compartments and mossy fiber terminal fields in lobules ii and iii of the rat cerebellar cortex: Spinocerebellar and cuneocerebellar projections , 1994, Neuroscience.

[15]  Martin Lauritzen,et al.  Brain Function and Neurophysiological Correlates of Signals Used in Functional Neuroimaging , 2003, The Journal of Neuroscience.

[16]  P. P. Edgar,et al.  Localization and characterization of 35S-t- butylbicyclophosphorothionate binding in rat brain: an autoradiographic study , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  P. Strata,et al.  The profiles of physiological events produced by a parallel fibre volley in the cerebellar cortex , 2004, Experimental Brain Research.

[19]  R. Eager,et al.  The mode of termination and temporal course of degeneration of cortical association pathways in the cerebellum of the cat , 1965, The Journal of comparative neurology.

[20]  Dieter Jaeger,et al.  No Parallel Fiber Volleys in the Cerebellar Cortex: Evidence from Cross-Correlation Analysis between Purkinje Cells in a Computer Model and in Recordings from Anesthetized Rats , 2003, Journal of Computational Neuroscience.

[21]  R. Llinás,et al.  Parallel fibre stimulation and the responses induced thereby in the Purkinje cells of the cerebellum , 2004, Experimental Brain Research.

[22]  Martin Lauritzen,et al.  Dissociation of spikes, synaptic activity, and activity-dependent increments in rat cerebellar blood flow by tonic synaptic inhibition , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[24]  S. Wang,et al.  Coincidence detection in single dendritic spines mediated by calcium release , 2000, Nature Neuroscience.

[25]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Attwell,et al.  The neural basis of functional brain imaging signals , 2002, Trends in Neurosciences.

[27]  Wade G. Regehr,et al.  Quantal events shape cerebellar interneuron firing , 2002, Nature Neuroscience.

[28]  C. Mathiesen,et al.  Temporal coupling between neuronal activity and blood flow in rat cerebellar cortex as indicated by field potential analysis , 2000, The Journal of physiology.

[29]  T. Ebner,et al.  Role of climbing fibers in determining the spatial patterns of activation in the cerebellar cortex to peripheral stimulation: an optical imaging study , 2000, Neuroscience.

[30]  B. Chance,et al.  The kinetics of flavoprotein and pyridine nucleotide oxidation in cardiac mitochondria in the presence of calcium , 1972, FEBS letters.

[31]  A. Parent,et al.  The compartmentalization of the monkey and rat cerebellar cortex: zebrin I and cytochrome oxidase , 1990, Brain Research.

[32]  K. Herrup,et al.  The compartmentalization of the cerebellum. , 1997, Annual review of neuroscience.

[33]  A. Konnerth,et al.  Subthreshold synaptic Ca2+ signalling in fine dendrites and spines of cerebellar Purkinje neurons , 1995, Nature.

[34]  Watt W Webb,et al.  Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. , 2002, Biophysical journal.

[35]  W. N. Ross,et al.  IPSPs strongly inhibit climbing fiber-activated [Ca2+]i increases in the dendrites of cerebellar Purkinje neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  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.

[37]  M. Häusser,et al.  Propagation of action potentials in dendrites depends on dendritic morphology. , 2001, Journal of neurophysiology.

[38]  F A Chaudhry,et al.  The Glutamate Transporter EAAT4 in Rat Cerebellar Purkinje Cells: A Glutamate-Gated Chloride Channel Concentrated near the Synapse in Parts of the Dendritic Membrane Facing Astroglia , 1998, The Journal of Neuroscience.

[39]  T L Babb,et al.  Increased glucose metabolism during long-duration recurrent inhibition of hippocampal pyramidal cells , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  J. Eccles,et al.  POSTSYNAPTIC INHIBITION OF CEREBELLAR PURKINJE CELLS. , 1964, Journal of neurophysiology.

[41]  Gang Chen,et al.  Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo. , 2004, Journal of neurophysiology.

[42]  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.

[43]  R. Llinás,et al.  The Cerebellum Revisited , 1992, Springer US.

[44]  R. Hawkes,et al.  Antigenic compartmentation in the mouse cerebellar cortex: Zebrin and HNK‐1 reveal a complex, overlapping molecular topography , 1993, The Journal of comparative neurology.

[45]  S. Palay,et al.  Chemical heterogeneity in cerebellar Purkinje cells: existence and coexistence of glutamic acid decarboxylase-like and motilin-like immunoreactivities. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[46]  A. Brodal,et al.  Olivocerebellar projection: a review. , 1980, Advances in anatomy, embryology, and cell biology.

[47]  J. Roder,et al.  Compartmentation of the mouse cerebellar cortex by neuronal calcium sensor‐1 , 2003, The Journal of comparative neurology.

[48]  Valentino Braitenberg,et al.  In Defense of the Cerebellum , 2002, Annals of the New York Academy of Sciences.

[49]  Florent Haiss,et al.  Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to posthypoxic myoclonus. , 2002, Advances in neurology.

[50]  S. Palay,et al.  The stellate cells of the rat's cerebellar cortex , 2004, Zeitschrift für Anatomie und Entwicklungsgeschichte.

[51]  D Jaarsma,et al.  The unipolar brush cells of the mammalian cerebellum and cochlear nucleus: cytology and microcircuitry. , 1997, Progress in brain research.

[52]  S. Palay,et al.  Cerebellar Cortex: Cytology and Organization , 1974 .

[53]  Michael Häusser,et al.  Feed‐forward inhibition shapes the spike output of cerebellar Purkinje cells , 2005, The Journal of physiology.

[54]  R. Hawkes,et al.  Zebrins: Molecular Markers of Compartmentation in the Cerebellum , 1992 .

[55]  A. Scheibel,et al.  Observations on the intracortical relations of the climbing fibers of the cerebellum. A Golgi study , 1954, The Journal of comparative neurology.

[56]  D. Laurie,et al.  The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  S. Wang,et al.  In vivo calcium imaging of circuit activity in cerebellar cortex. , 2005, Journal of neurophysiology.

[58]  J. Jansen,et al.  The Comparative Anatomy and Histology of the Cerebellum: The Human Cerebellum, Cerebellar Connections, and Cerebellar Cortex , 1972 .