Topography and Reciprocal Activity of Cerebellar Purkinje Cells in the Uvula-Nodulus Modulated by Vestibular Stimulation

1997 ◽  
Vol 78 (6) ◽  
pp. 3083-3094 ◽  
Author(s):  
H. Fushiki ◽  
N. H. Barmack
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Semicircular Canals ◽  
Vertical Axis ◽  
Longitudinal Axis ◽  
Vestibular Stimulation ◽  
Climbing Fiber ◽  
Null Plane ◽  
Cerebellar Purkinje Cells ◽  
Vertical Semicircular Canals

Fushiki, H. and N. H. Barmack. Topography and reciprocal activity of cerebellar Purkinje cells in the uvula-nodulus modulated by vestibular stimulation. J. Neurophysiol. 78: 3083–3094, 1997. In the rabbit uvula-nodulus, vestibular and optokinetic information is mapped onto parasagittal zones by climbing fibers. These zones are related functionally to different pairs of vertical semicircular canals, otolithic inputs and horizontal optokinetic inputs. Vestibular stimulation restricted to one of these zones modulates climbing fiber responses (CFRs). Within each of these zones, simple spikes (SSs) are modulated reciprocally with CFRs. In rabbits anesthetized with chloralose-urethan, we have used vestibular and optokinetic stimulation to evoke CFRs within a parasagittal zone while recording from Purkinje cells in adjacent zones. We have examined whether the CFRs evoked by vestibular stimulation in one zone influence the SSs of an adjacent zone. CFRs and SSs were recorded during roll vestibular stimulation. The orientation of the head of the rabbit with respect to the axis of rotation was varied systematically so that a climbing fiber null plane could be determined. This null plane was the orientation of the head about the vertical axis at which no modulation of the CFR was observed during rotation about the longitudinal axis of the vestibular rate table. In the left uvula-nodulus, a medial sagittal strip extending through all the folia contained Purkinje cells with CFRs that had optimal planes of stimulation coplanar with the left posterior-right anterior semicircular canals (LPC-RAC). Lateral to this strip was a strip of Purkinje cells with CFRs that were characterized by optimal planes corresponding to stimulation of the left anterior-right posterior semicircular canals (LAC-RPC). SSs in Purkinje cells were modulated out of phase with CFRs from the same Purkinje cell. The depth of modulation of both CFRs and SSs was reduced during rotation in the climbing fiber “null plane”. The depth of modulation of SSs was greatest when recorded from Purkinje cells located at the center of semicircular canal-related strip. We observed that 1) all folia of the uvula-nodulus receive vestibular climbing fiber inputs; 2) these climbing fiber inputs convey information from the vertical semicircular canals and otoliths but not the horizontal semicircular canals; 3) CFRs evoked in a particular sagittal zone do not influence SSs in adjacent zones; 4) modulation of a CFRs in a particular Purkinje cell can occur without modulation of SSs in the same Purkinje cell, although modulation of SSs was not observed in the absence of CFR modulation; and 5) modulation of SSs sometimes preceded that of CFRs in the same cell, implying that interneuronal pathways may contribute to SS modulation. Climbing fiber-driven Golgi cells, the inhibitory axon terminals of which end on granule cell dendrites in the classic glomerular synapse, may provide this interneuronal mechanism.

Vestibular Signals in the Parasolitary Nucleus

2000 ◽  
Vol 83 (6) ◽  
pp. 3559-3569 ◽  
Author(s):  
N. H. Barmack ◽  
V. Yakhnitsa
Keyword(s):  
Inferior Olive ◽  
Granule Cells ◽  
Vestibular Nucleus ◽  
Semicircular Canals ◽  
Longitudinal Axis ◽  
Vestibular Stimulation ◽  
Primary Afferents ◽  
Climbing Fiber ◽  
Large Sphere ◽  
Optimal Response

Vestibular primary afferents project to secondary vestibular neurons located in the vestibular complex. Vestibular primary afferents also project to the uvula-nodulus of the cerebellum where they terminate on granule cells. In this report we describe the physiological properties of neurons in a “new” vestibular nucleus, the parasolitary nucleus (Psol). This nucleus consists of 2,300 GABAergic neurons that project onto the ipsilateral inferior olive (β-nucleus and dorsomedial cell column) as well as the nucleus reticularis gigantocellularis. These olivary neurons are the exclusive source of vestibularly modulated climbing fiber inputs to the cerebellum. We recorded the activity of Psol neurons during natural vestibular stimulation in anesthetized rabbits. The rabbits were placed in a three-axis rate table at the center of a large sphere, permitting vestibular and optokinetic stimulation. We recorded from 74 neurons in the Psol and from 23 neurons in the regions bordering Psol. The activity of 72/74 Psol neurons and 4/23 non-Psol neurons was modulated by vestibular stimulation in either the pitch or roll planes but not the horizontal plane. Psol neurons responded in phase with ipsilateral side-down head position or velocity during sinusoidal stimulation. Approximately 80% of the recorded Psol neurons responded to static roll-tilt. The optimal response planes of evoked vestibular responses were inferred from measurement of null planes. Optimal response planes usually were aligned with the anatomical orientation of one of the two ipsilateral vertical semicircular canals. The frequency dependence of null plane measurements indicated a convergence of vestibular information from otoliths and semicircular canals. None of the recorded neurons evinced optokinetic sensitivity. These results are consistent with the view that Psol neurons provide the vestibular signals to the inferior olive that eventually reached the cerebellum in the form of modulated climbing fiber discharges. These signals provide information about spatial orientation about the longitudinal axis.

Vestibular and visual climbing fiber signals evoked in the uvula-nodulus of the rabbit cerebellum by natural stimulation

1995 ◽  
Vol 74 (6) ◽  
pp. 2573-2589 ◽  
Author(s):  
N. H. Barmack ◽  
H. Shojaku
Keyword(s):  
Purkinje Cells ◽  
Semicircular Canal ◽  
Mossy Fiber ◽  
Semicircular Canals ◽  
Longitudinal Axis ◽  
Climbing Fiber ◽  
Optokinetic Stimulation ◽  
Simple Spike ◽  
Postural Responses ◽  
Stimulation Of

1. The cerebellar uvula-nodulus receives vestibular projections from primary and secondary vestibular afferents as well as vestibularly related climbing fibers. It also receives visually related information from climbing fiber pathways. In this experiment we investigated how this information is mapped onto the uvula-nodulus. We studied the specificity, dynamics, and topographic distribution of climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal responses evoked by vestibular and optokinetic stimulation in rabbits anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the ventral uvula and nodulus. These responses were evoked during static roll tilt of the rabbit about a longitudinal axis and by sinusoidal oscillation about the longitudinal axis. Purely static responses were attributed to stimulation of the utricular otolith by the linear acceleration of gravity. CFRs that lacked a static component were attributed to activation of the semicircular canals. 3. Using a "null technique" we showed that the canal-sensitive CFRs were caused by stimulation of the anterior or posterior semicircular canals. Of the CFRs classified as canal related, 96% could be attributed to stimulation of the vertical semicircular canals. 4. Increases in CFRs were correlated with decreases in simple spike responses in half the Purkinje cells from which we recorded. These climbing-fiber-induced pauses in simple spikes occurred during spontaneous climbing fiber discharge as well as during climbing fiber discharge evoked by vestibular stimulation. The duration of this pause was inversely proportional to the spontaneous level of simple spikes before the occurrence of a CFR. In the other half of the recorded population of Purkinje cells, vestibularly driven CFRs did not alter the simple spike responses. 5. Vestibularly and visually mediated CFRs were topographically represented on the surface of the uvula-nodulus. CFRs driven by ipsilateral otolithic inputs were distributed over the entire mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral posterior semicircular canal were distributed in a sagittal strip approximately 1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven exclusively by horizontal, posterior-->anterior optokinetic stimulation of the ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs driven by the ipsilateral anterior semicircular canal were found in a sagittal strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The sagittal, topographically arrayed climbing fiber strips effectively map a mediolateral gradient of possible postural responses based on vestibular and optokinetic information.

scholarly journals Flocculus Purkinje cell signals in mouse Cacna1a calcium channel mutants of escalating severity: an investigation of the role of firing irregularity in ataxia

2014 ◽  
Vol 112 (10) ◽  
pp. 2647-2663 ◽  
Author(s):  
John S. Stahl ◽  
Zachary C. Thumser
Keyword(s):  
Purkinje Cell ◽  
Calcium Channel ◽  
Purkinje Cells ◽  
Vertical Axis ◽  
Modulation Amplitude ◽  
Cerebellar Dysfunction ◽  
Optokinetic Reflex ◽  
Firing Irregularity ◽  
Cerebellar Purkinje Cells ◽  
Cell Signals

Mutation of the Cacna1a gene for the P/Q (CaV2.1) calcium channel invariably leads to cerebellar dysfunction. The dysfunction has been attributed to disrupted rhythmicity of cerebellar Purkinje cells, but the hypothesis remains unproven. If irregular firing rates cause cerebellar dysfunction, then the irregularity and behavioral deficits should covary in a series of mutant strains of escalating severity. We compared firing irregularity in floccular and anterior vermis Purkinje cells in the mildly affected rocker and moderately affected tottering Cacna1a mutants and normal C57BL/6 mice. We also measured the amplitude and timing of modulations of floccular Purkinje cell firing rate during the horizontal vestibuloocular reflex (VOR, 0.25–1 Hz) and the horizontal and vertical optokinetic reflex (OKR, 0.125–1 Hz). We recorded Purkinje cells selective for rotational stimulation about the vertical axis (VAPCs) and a horizontal axis (HAPCs). Irregularity scaled with behavioral deficit severity in the flocculus but failed to do so in the vermis, challenging the irregularity hypothesis. Mutant VAPCs exhibited unusually strong modulation during VOR and OKR, the response augmentation scaling with phenotypic severity. HAPCs exhibited increased OKR modulation but in tottering only. The data contradict prior claims that modulation amplitude is unaffected in tottering but support the idea that attenuated compensatory eye movements in Cacna1a mutants arise from defective transfer of Purkinje cell signals to downstream circuitry, rather than attenuated synaptic transmission within the cerebellar cortex. Shifts in the relative sizes of the VAPC and HAPC populations raise the possibility that Cacna1a mutations influence the development of floccular zone architecture.

scholarly journals Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD

2013 ◽  
Vol 109 (5) ◽  
pp. 1333-1342 ◽  
Author(s):  
Qionger He ◽  
Heather Titley ◽  
Giorgio Grasselli ◽  
Claire Piochon ◽  
Christian Hansel
Keyword(s):  
Nmda Receptor ◽  
Purkinje Cell ◽  
Nmda Receptors ◽  
Purkinje Cells ◽  
Climbing Fiber ◽  
Receptor Signaling ◽  
Whole Cell Patch Clamp ◽  
Bath Application ◽  
Cerebellar Purkinje Cells ◽  
Circuit Function

Ethanol profoundly influences cerebellar circuit function and motor control. It has recently been demonstrated that functional N-methyl-d-aspartate (NMDA) receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in the adult cerebellum. Using whole cell patch-clamp recordings from mouse cerebellar slices, we examined whether ethanol can affect NMDA receptor signaling in mature Purkinje cells. NMDA receptor-mediated currents were isolated by bath application of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzol[f]quinoxaline (NBQX). The remaining d-2-amino-5-phosphonovaleric acid (d-APV)-sensitive current was reduced by ethanol at concentrations as low as 10 mM. At a concentration of 50 mM ethanol, the blockade of d-APV-sensitive CF-excitatory postsynaptic currents was significantly stronger. Ethanol also altered the waveform of CF-evoked complex spikes by reducing the afterdepolarization. This effect was not seen when NMDA receptors were blocked by d-APV before ethanol wash-in. In contrast to CF synaptic transmission, parallel fiber (PF) synaptic inputs were not affected by ethanol. Finally, ethanol (10 mM) impaired long-term depression (LTD) at PF to Purkinje cell synapses as induced under control conditions by paired PF and CF activity. However, LTD induced by pairing PF stimulation with depolarizing voltage steps (substituting for CF activation) was not blocked by ethanol. These observations suggest that the sensitivity of cerebellar circuit function and plasticity to low concentrations of ethanol may be caused by an ethanol-mediated impairment of NMDA receptor signaling at CF synapses onto cerebellar Purkinje cells.

Normal adult climbing fiber monoinnervation of cerebellar Purkinje cells in mice lacking MHC class I molecules

2008 ◽  
Vol 68 (8) ◽  
pp. 997-1006 ◽  
Author(s):  
Mathieu Letellier ◽  
Melina L. Willson ◽  
Vanessa Gautheron ◽  
Jean Mariani ◽  
Ann M. Lohof
Keyword(s):  
Purkinje Cells ◽  
Mhc Class I ◽  
Climbing Fiber ◽  
Class I ◽  
Normal Adult ◽  
Cerebellar Purkinje Cells ◽  
Mhc Class I Molecules

scholarly journals Activation of MAP3K DLK and LZK in Purkinje Cells Causes Rapid and Slow Degeneration Depending on Signaling Strength

2020 ◽  
Author(s):  
Yunbo Li ◽  
Erin M Ritchie ◽  
Christopher L. Steinke ◽  
Cai Qi ◽  
Lizhen Chen ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Leucine Zipper ◽  
Activity Levels ◽  
Cell Type ◽  
Cell Degeneration ◽  
Mechanistic Basis ◽  
Cerebellar Purkinje Cells ◽  
Jnk Activation

SummaryThe conserved MAP3K Dual leucine zipper kinases can activate JNK via MKK4 or MKK7. Vertebrate DLK and LZK share similar biochemical activities and undergo auto-activation upon increased expression. Depending on cell-type and nature of insults DLK and LZK can induce pro-regenerative, pro-apoptotic or pro-degenerative responses, although the mechanistic basis of their action is not well understood. Here, we investigated these two MAP3Ks in cerebellar Purkinje cells using loss- and gain-of function mouse models. While loss of each or both kinases does not cause discernible defects in Purkinje cells, activating DLK causes rapid death and activating LZK leads to slow degeneration. Each kinase induces JNK activation and caspase-mediated apoptosis independent of each other. Significantly, deleting CELF2, which regulates alternative splicing of Mkk7, strongly attenuates Purkinje cell degeneration induced by activation of LZK, but not DLK. Thus, controlling the activity levels of DLK and LZK is critical for neuronal survival and health.

scholarly journals Predictive and reactive reward signals conveyed by climbing fiber inputs to cerebellar Purkinje cells

2019 ◽  
Vol 22 (6) ◽  
pp. 950-962 ◽  
Author(s):  
Dimitar Kostadinov ◽  
Maxime Beau ◽  
Marta Blanco-Pozo ◽  
Michael Häusser
Keyword(s):  
Purkinje Cells ◽  
Climbing Fiber ◽  
Cerebellar Purkinje Cells

scholarly journals Expression of the yes proto-oncogene in cerebellar Purkinje cells.

1989 ◽  
Vol 9 (10) ◽  
pp. 4545-4549 ◽  
Author(s):  
M Sudol ◽  
C F Kuo ◽  
L Shigemitsu ◽  
A Alvarez-Buylla
Keyword(s):  
In Situ Hybridization ◽  
Purkinje Cell ◽  
Gene Product ◽  
Purkinje Cells ◽  
Immunofluorescent Staining ◽  
Cell Degeneration ◽  
Functional Studies ◽  
Cerebellar Purkinje Cells ◽  
The Brain

To identify the kinds of cells in the brain that express the yes proto-oncogene, we examined chicken brains by using immunofluorescent staining and in situ hybridization. Both approaches showed that the highest level of the yes gene product was in cerebellar Purkinje cells. In addition, we analyzed Purkinje cell degeneration (pcd) mutant mice. The level of yes mRNA in cerebella of pcd mutants was four times lower than that found in cerebella of normal littermates. Our studies point to Purkinje cells as an attractive model for functional studies of the yes protein.

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