scholarly journals Inhibition gates supralinear Ca2+ signaling in Purkinje cell dendrites during practiced movements

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Michael A Gaffield ◽  
Matthew J M Rowan ◽  
Samantha B Amat ◽  
Hirokazu Hirai ◽  
Jason M Christie
Keyword(s):  
Neural Circuit ◽  
Molecular Layer ◽  
Climbing Fiber ◽  
Parallel Fiber ◽  
Climbing Fibers ◽  
Parallel Fibers ◽  
Motor Behaviors ◽  
Sensorimotor Information ◽  
Purkinje Cell Dendrites

Motor learning involves neural circuit modifications in the cerebellar cortex, likely through re-weighting of parallel fiber inputs onto Purkinje cells (PCs). Climbing fibers instruct these synaptic modifications when they excite PCs in conjunction with parallel fiber activity, a pairing that enhances climbing fiber-evoked Ca2+ signaling in PC dendrites. In vivo, climbing fibers spike continuously, including during movements when parallel fibers are simultaneously conveying sensorimotor information to PCs. Whether parallel fiber activity enhances climbing fiber Ca2+ signaling during motor behaviors is unknown. In mice, we found that inhibitory molecular layer interneurons (MLIs), activated by parallel fibers during practiced movements, suppressed parallel fiber enhancement of climbing fiber Ca2+ signaling in PCs. Similar results were obtained in acute slices for brief parallel fiber stimuli. Interestingly, more prolonged parallel fiber excitation revealed latent supralinear Ca2+ signaling. Therefore, the balance of parallel fiber and MLI input onto PCs regulates concomitant climbing fiber Ca2+ signaling.

scholarly journals Conversion of graded presynaptic climbing fiber activity into graded postsynaptic Ca2+ signals by Purkinje cell dendrites

2018 ◽  
Author(s):  
Michael A. Gaffield ◽  
Jason M. Christie
Keyword(s):  
Purkinje Cell ◽  
Inferior Olive ◽  
Mossy Fiber ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
Dependent Manner ◽  
Related Information ◽  
External Stimuli ◽  
Purkinje Cell Dendrites

AbstractThe brain must make sense of external stimuli to generate relevant behavior. We used a combination of in vivo approaches to investigate how the cerebellum processes sensory-related information. We found that the inferior olive encodes contexts of sensory-associated external cues in a graded manner, apparent in the presynaptic activity of their axonal projections in the cerebellar cortex. Further, individual climbing fibers were broadly responsive to different sensory modalities but relayed sensory-related information to the cortex in a lobule-dependent manner. Purkinje cell dendrites faithfully transformed this climbing fiber activity into dendrite-wide Ca2+ signals without a direct contribution from the mossy fiber pathway. These results demonstrate that the size of climbing fiber-evoked Ca2+ signals in Purkinje cell dendrites is largely determined by the firing level of climbing fibers. This coding scheme emphasizes the overwhelming role of the inferior olive in generating salient signals useful for instructing plasticity and learning.

scholarly journals Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Angela K Nietz ◽  
Jada H Vaden ◽  
Luke T Coddington ◽  
Linda Overstreet-Wadiche ◽  
Jacques I Wadiche
Keyword(s):  
Feedback Inhibition ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Cell Activity ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
In Vivo Studies ◽  
Golgi Cell ◽  
Golgi Cells ◽  
Fiber Stimulation

Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.

scholarly journals Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Eljo Van Battum ◽  
Celine Heitz-Marchaland ◽  
Yvrick Zagar ◽  
Stéphane Fouquet ◽  
Rohini Kuner ◽  
...  
Keyword(s):  
3D Imaging ◽  
Imaging Techniques ◽  
Molecular Layer ◽  
Conditional Knockout ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cerebellar Granule ◽  
External Granule Layer ◽  
Purkinje Cell Dendrites

Plexin-B2 deletion leads to aberrant lamination of cerebellar granule neurons (CGNs) and Purkinje cells. Although in the cerebellum Plexin-B2 is only expressed by proliferating CGN precursors in the outer external granule layer (oEGL), its function in CGN development is still elusive. Here, we used 3D imaging, in vivo electroporation and live-imaging techniques to study CGN development in novel cerebellum-specific Plxnb2 conditional knockout mice. We show that proliferating CGNs in Plxnb2 mutants not only escape the oEGL and mix with newborn postmitotic CGNs. Furthermore, motility of mitotic precursors and early postmitotic CGNs is altered. Together, this leads to the formation of ectopic patches of CGNs at the cerebellar surface and an intermingling of normally time-stamped parallel fibers in the molecular layer (ML), and aberrant arborization of Purkinje cell dendrites. There results suggest that Plexin-B2 restricts CGN motility and might have a function in cytokinesis.

Imaging parallel fiber and climbing fiber responses and their short-term interactions in the mouse cerebellar cortex in vivo

Neuroscience ◽  
2004 ◽  
Vol 126 (1) ◽  
pp. 213-227 ◽  
Author(s):  
R.L Dunbar ◽  
G Chen ◽  
W Gao ◽  
K.C Reinert ◽  
R Feddersen ◽  
...  
Keyword(s):  
Cerebellar Cortex ◽  
Climbing Fiber ◽  
Parallel Fiber ◽  
Short Term ◽  
Climbing Fiber Responses

scholarly journals Gating of neural error signals during motor learning

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Rhea R Kimpo ◽  
Jacob M Rinaldi ◽  
Christina K Kim ◽  
Hannah L Payne ◽  
Jennifer L Raymond
Keyword(s):  
Motor Learning ◽  
Climbing Fiber ◽  
Climbing Fibers ◽  
Motor Memory ◽  
Ocular Reflex ◽  
Learning Tasks ◽  
Performance Errors ◽  
Vestibulo Ocular Reflex

Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors.

scholarly journals Ketamine and Xylazine Depress Sensory-Evoked Parallel Fiber and Climbing Fiber Responses

2007 ◽  
Vol 98 (3) ◽  
pp. 1697-1705 ◽  
Author(s):  
Fredrik Bengtsson ◽  
Henrik Jörntell
Keyword(s):  
Mossy Fiber ◽  
Physiological Activity ◽  
Field Potential ◽  
Climbing Fiber ◽  
Parallel Fiber ◽  
Field Potentials ◽  
In Vivo Experiments ◽  
Sensory Evoked ◽  
Climbing Fiber Responses

The last few years have seen an increase in the variety of in vivo experiments used for studying cerebellar physiological mechanisms. A combination of ketamine and xylazine has become a particularly popular form of anesthesia. However, because nonanesthetized control conditions are lacking in these experiments, so far there has been no evaluation of the effects of these drugs on the physiological activity in the cerebellar neuronal network. In the present study, we used the mossy fiber, parallel fiber, and climbing fiber field potentials evoked in the nonanesthetized, decerebrated rat to serve as a control condition against which the effects of intravenous drug injections could be compared. All anesthetics were applied at doses required for normal maintenance of anesthesia. We found that ketamine substantially depressed the evoked N3 field potential, which is an indicator of the activity in the parallel fiber synapses (−40%), and nearly completely abolished evoked climbing fiber field potentials (−90%). Xylazine severely depressed the N3 field (−75%) and completely abolished the climbing fiber field (−100%). In a combination commonly used for general anesthesia (20:1), ketamine–xylazine injections also severely depressed the N3 field (−75%) and nearly completely abolished the climbing fiber field (−90%). We also observed that lowered body and surface temperatures (<34°C) resulted in a substantial depression of the N3 field (−50%). These results urge for some caution in the interpretations of studies on cerebellar network physiology performed in animals anesthetized with these drugs.

Laminar analysis of activity-dependent increases of CBF in rat cerebellar cortex: dependence on synaptic strength

1997 ◽  
Vol 273 (3) ◽  
pp. H1166-H1176 ◽  
Author(s):  
N. Akgoren ◽  
C. Mathiesen ◽  
I. Rubin ◽  
M. Lauritzen
Keyword(s):  
Electrical Stimulation ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Synaptic Strength ◽  
Parallel Fiber ◽  
Climbing Fibers ◽  
Parallel Fibers ◽  
Doppler Flowmetry ◽  
Activity Dependent ◽  
Stimulation Of

The purpose of the present study was to examine mechanisms of activity-dependent changes of cerebral blood flow (CBF) in rat cerebellar cortex by laser-Doppler flowmetry, using two synaptic inputs that excite different regions of the same target cell and with different synaptic strength. The apical part of Purkinje cells was activated by electrical stimulation of parallel fibers, whereas the cell soma and the proximal part of the dendritic tree were activated by climbing fibers using harmaline (40 mg/kg ip) or electrical stimulation of the inferior olive. Glass microelectrodes were used for recordings of field potentials and single-unit activity of Purkinje cells. CBF increases evoked by parallel fibers were most pronounced in the upper cortical layers. In contrast, climbing fiber stimulation increased CBF in the entire cortex. Inhibition of nitric oxide (NO) synthase activity by NG-nitro-L-arginine (L-NNA) or guanylate cyclase activity by 1H-[1,2,4(oxadiazolo)4,3-a]quinoxaline-1-one did not affect basal or harmaline-induced Purkinje cell activity but attenuated harmaline- and parallel fiber-evoked CBF increases by approximately 40-50%. Application of 8-(p-sulfophenyl)theophylline and adenosine deaminase reduced the harmaline-evoked CBF increase without any effect on the parallel fiber-evoked CBF response. The results suggest that CBF increases elicited by activation of Purkinje cells are partially mediated by the NO-guanosine 3',5'-cyclic monophosphate system independent of the input function but that adenosine contributes as well when climbing fibers are activated. This is the first demonstration of variations of coupling as a function of postsynaptic activity in the same cell.

Involvement of Kv1 Potassium Channels in Spreading Acidification and Depression in the Cerebellar Cortex

2005 ◽  
Vol 94 (2) ◽  
pp. 1287-1298 ◽  
Author(s):  
Gang Chen ◽  
Wangcai Gao ◽  
Kenneth C. Reinert ◽  
Laurentiu S. Popa ◽  
Claudia M. Hendrix ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Cerebellar Cortex ◽  
Molecular Layer ◽  
Neutral Red ◽  
Parallel Fiber ◽  
Null Mouse ◽  
Gabaergic Neurotransmission ◽  
Multiple Cycles

Spreading acidification and depression (SAD) is a form of propagated activity in the cerebellar cortex characterized by acidification and a transient depression in excitability. This study investigated the role of Kv1 potassium channels in SAD using neutral red, flavoprotein autofluorescence, and voltage-sensitive dye optical imaging in the mouse cerebellar cortex, in vivo. The probability of evoking SAD was greatly increased by blocking Kv1.1 as well as Kv1.2 potassium channels by their specific blockers dendrotoxin K (DTX-K) and tityustoxin (TsTX), respectively. DTX-K not only greatly lowered the threshold for evoking SAD but also resulted in multiple cycles of spread and spontaneous SAD. The occurrence of spontaneous SAD originating from spontaneous parallel fiber-like beams of activity suggests that blocking Kv1 channels increased parallel fiber excitability. This was confirmed by the generation of parallel fiber-like beams with the microinjection of glutamate into the upper molecular layer in the presence of DTX-K. The dramatic effects of DTX-K suggest a possible connection between SAD and episodic ataxia type 1 (EA1), a Kv1.1 potassium channelopathy. The threshold for evoking SAD was significantly lowered in the Kv1.1 heterozygous knockout mouse compared with wild-type littermates. Carbamazepine and acetazolamide, both effective in the treatment of EA1, significantly decreased the likelihood of evoking SAD. Blocking GABAergic neurotransmission did not alter the effectiveness of DTX-K. The cyclin D2 null mouse, which lacks cerebellar stellate cells, also exhibited SAD. Therefore blocking Kv1 potassium channels establishes the conditions needed to generate SAD. Furthermore, the results are consistent with the hypothesis that SAD may underlie the transient attacks of ataxia characterizing EA1.

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