Occurrence of long-term depression in the cerebellar flocculus during adaptation of optokinetic response

Inoshita, Takuma; Hirano, Tomoo

doi:10.7554/elife.36209

Cited by 48 publications

(39 citation statements)

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“…Many previous studies, using various LTD-deficient animal models, have reported that synaptic plasticity at the PF-PC synapse is strongly correlated with motor learning (Boyden et al, 2006; De Zeeuw et al, 1998; Hansel et al, 2006). Optokinetic response (OKR)-induced synaptic LTD in the cerebellar cortex has been recently reported (Inoshita & Hirano, 2018), but plasticity induced by the VOR adaptation has yet to be proved. Late-phase LTD has also been implicated in VOR memory consolidation (Ahn, Ginty, & Linden, 1999; Boyden et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

“…It is widely believed that the cellular basis of memory is derived from modifications of synaptic transmission, such as long-term potentiation (LTP) and long-term depression (LTD) (Kandel, Dudai, & Mayford, 2014). For decades, since Ito proposed the flocculus hypothesis (Ito, 1982), numerous studies have demonstrated that synaptic plasticity between parallel fibers (PFs) and cerebellar Purkinje cells (PCs) is the key mechanism of vestibule-ocular reflex (VOR) adaptation (De Zeeuw et al, 1998; Hansel et al, 2006; Inoshita & Hirano, 2018; Kakegawa et al, 2018; Schonewille et al, 2010). However, several works proposed that the synaptic plasticity at the PF-PC synapse is not sufficient to explain motor learning (Ito, 2013; Ke, Guo, & Raymond, 2009; Schonewille et al, 2011; Wulff et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic plasticity of cerebellar Purkinje cells in motor learning circuits

Jang

Shim

Kim

2019

Preprint

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19Intrinsic plasticity of cerebellar Purkinje cells (PCs) is recently highlighted in the cerebellar local circuits, however, 20 its physiological impact on the cerebellar learning and memory remains elusive. Using a mouse model of memory 21 consolidation deficiency, we found that the intrinsic plasticity of PCs may be involved in motor memory 22 consolidation. Gain-up training of the vestibulo-ocular reflex produced a decrease in the synaptic weight of PCs 23 in both the wild-type and knockout groups. However, intrinsic plasticity was impaired only in the knockout mice. 24Furthermore, the observed defects in the intrinsic plasticity of PCs led to the formation of improper neural 25 plasticity in the vestibular nucleus (VN) neurons. Our results suggest that the synergistic modulation of intrinsic 26 and synaptic plasticity in PCs is required for the changes in the local connectivity between the cerebellum and 27 VN that contribute to the long-term storage of motor memory. 55the impact of intrinsic plasticity within the motor learning circuits, we assessed neural activity in the VN 56 neurons following the gain-increase learning. Firing rate potentiation was gradually developed over time, 57 3 and excitatory synaptic transmission was also increased after learning. Notably, neither synaptic plasticity 58 nor intrinsic plasticity of the VN neurons was observed in STIM PKO mice. This implies that the subsequent 59 increases in the neural activity in the VN neurons may be derived from changes in the cortical output, as 60 determined by the intrinsic plasticity of the cerebellar PCs.61 62 Materials and Methods 63 64 Animal model 65 We crossed homozygous PCP2-Cre line (B6.129-Tg(Pcp2-cre)2Mpin/J line, Jackson Laboratory) with the 66 STIM1-floxed line (C57BL/6 background) to generate PC-specific STIM1 knockout line as our recent study (Ryu 67 et al., 2017). Only male mice were used in all experiments, and procedures were approved by the Institutional 68 69 Surgery 70All surgical procedure was similar to our previous paper (see Ryu et al., 2017). Surgery for head fixation has been 71 done at 7-to 8-weeks-old. Zoletil (Zoletil 50, Virbac, 15mg/kg) + xylazine (Rompun, Bayer, 15mg/kg) mixture 72 was applied to anesthetize mice through intraperitoneal injection. After surgery, 24 to 48 hours of recovery time 73 were given to mice. 74Behavior test 75The installation and most of procedure were similar to our previous paper (see Ryu et al., 2017). To control 76 pupil dilatation, physostigmine salicylate solution (Eserine; Sigma Aldrich) was treated with brief isoflurane 77 anesthetization, and at least 20mins were given to washout the side-effect of anesthetization. The concentration 78 of eserine solution was constantly increased from 0.1%, 0.15% and 0.2% because of drug resistance. Two sessions 79 of acclimation were performed. At first, the mouse was fixed onto a restrainer for 15 minutes and experienced 80 light on and off, several brief visual and vestibular stimulation for checking surgical failure. Secondly, calibration 81...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intrinsic plasticity of cerebellar Purkinje cells in motor learning circuits

Jang

Shim

Kim

2019

Preprint

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“…Since then, the idea that the cerebellum learns by sculpting away synapses that cause errors through this anti-Hebbian form of synaptic plasticity has had a powerful influence on the cerebellar field. LTD and its links to cerebellum-dependent learning have been extensively investigated, yet there is still much disagreement about whether and how LTD at parallel fiber-to-Purkinje cell synapses contributes to learning [6,7,16–25,8,26–30,9–15]. Here, we review findings that suggest a path toward a Clearer and more sophisticated understanding of the contribution of LTD to cerebellum-dependent learning.…”

Section: Main Textmentioning

confidence: 98%

“…A variety of recording, stimulation and perturbation approaches have yielded considerable, convergent evidence for a role of LTD in learning [10,11,37–46,15,18,31–36] but also yielded results that call into question the necessity of parallel fiber-to-Purkinje cell LTD for learning [13,40,41,47–49]. One of the most widely used experimental approaches has been to employ pharmacological or molecular-genetic techniques to perturb LTD, and then test the effects on one or more cerebellum-dependent learning tasks.…”

Section: Main Textmentioning

confidence: 99%

Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

Suvrathan

Raymond

2018

Cerebellum

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Climbing fiber-driven long-term depression (LTD) of parallel fiber synapses onto cerebellar Purkinje cells has long been investigated as a putative mechanism of motor learning. We recently discovered that the rules governing the induction of LTD at these synapses vary across different regions of the cerebellum. Here, we discuss the design of LTD induction protocols in light of this heterogeneity in plasticity rules. The analytical advantages of the cerebellum provide an opportunity to develop a deeper understanding of how the specific plasticity rules at synapses support the implementation of learning.

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“…This result predicts a reduced EPSCs in PF-PC synapses after HOKR adaptation. Indeed, a further study using conventional acute slice preparation showed the decrease in quantal EPSC amplitude of PF-PC synapses in the flocculus of mice after HOKR training, but the reduction was below 10%, much lower than the value expected from the reduction of AMPAR density 29 .…”

Section: Long-term Plasticity Induced By Hokr Adaptationmentioning

confidence: 91%

Advantages of acute brain slices prepared at physiological temperature in characterization of synaptic functions

Eguchi

Velicky

Hollergschwandtner

et al. 2019

Preprint

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Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and 2 reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability and higher detectability of long-term depression after motor learning compared with slices prepared at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.

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Occurrence of long-term depression in the cerebellar flocculus during adaptation of optokinetic response

Cited by 48 publications

References 39 publications

Intrinsic plasticity of cerebellar Purkinje cells in motor learning circuits

Intrinsic plasticity of cerebellar Purkinje cells in motor learning circuits

Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

Advantages of acute brain slices prepared at physiological temperature in characterization of synaptic functions

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