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Organization of inhibition in the cerebellar cortex

小脑皮质的抑制组织

基本信息

批准号：
10877237
负责人：
Jason M Christie
金额：
$ 57.07万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10877237
关键词：
Organization inhibition cerebellar cortex

项目摘要

Project Summary The project remains the same as the original application. Below is a summary overview. Our long-term goal is to generate a complete understanding of how the cerebellum learns to improve movement in response to motor errors. Climbing fibers are thought to play an essential role in this process because they fire during erroneous movement. Their activity reliably excites Purkinje cells, eliciting calcium spikes in their dendrites that can trigger long-term synaptic plasticity at coactive parallel fiber inputs. Plasticity induction ultimately leads to corrective behavior by altering the cerebellum's response to sensorimotor stimuli that predict mistakes. Importantly, inhibition from molecular layer interneurons (MLIs) that target Purkinje cell dendrites suppresses climbing-fiber-evoked calcium signaling, opposing or `gating' plasticity induction. Because MLIs are activated by movement, this suggests Purkinje cell disinhibition is required during motor learning. As MLIs inhibit other MLIs, their interconnections could support a circuit for Purkinje cell disinhibition during behavior. The objective of this proposal is to examine the possibility that MLI circuits are structured to support a context-dependent engagement that allows climbing fibers to instruct plasticity and learning in response to motor errors. To accomplish this, we will employ a multidisciplinary approach using cutting-edge molecular-genetic techniques, functional recordings, circuit mapping, and behavioral analysis. In the first aim, we will test whether ablating MLI-to-MLI connections that normally support Purkinje cell disinhibition affect the ability of climbing fibers to evoke full-blown calcium signals in response to motor errors, and whether loss of MLI-MLI circuit function affects cerebellar-dependent motor learning. In the second aim, we will establish an MLI taxonomy and use it to survey for previously unknown MLI subtypes. We will also use functional recordings to test whether there is evidence for bias connectivity within the MLI network that supports a dedicated circuit for Purkinje cell disinhibition. In the third aim, we will use anatomical tracing to ascertain the MLI connectome. In this way we will determine if there is a structural basis for the independent actuation of MLI subtypes through their afferent inputs and the cell-type selectivity of their efferent outputs. Completion of these aims will lead to an unprecedented understanding of the organizational logic of the molecular layer. In particular, we expect to reveal how circuits within the molecular layer control the induction of climbing-fiber- mediated learning. This knowledge will not only help develop theories/models of cerebellum function but will also provide insight into the processes underlying learning in general.

项目总结

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Autonomous Purkinje cell activation instructs bidirectional motor learning through evoked dendritic calcium signaling.

DOI：
10.1038/s41467-021-22405-8
发表时间：
2021-04-12
期刊：
Nature communications
影响因子：
16.6
作者：
Bonnan A;Rowan MMJ;Baker CA;Bolton MM;Christie JM
通讯作者：
Christie JM

Molecular layer disinhibition unlocks climbing-fiber-instructed motor learning in the cerebellum.

分子层去抑制开启了小脑中攀爬纤维指导的运动学习。

DOI：
10.1101/2023.08.04.552059
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Zhang,Ke;Yang,Zhen;Gaffield,MichaelA;Gross,GarrettG;Arnold,DonB;Christie,JasonM
通讯作者：
Christie,JasonM

A deep learning approach to identifying immunogold particles in electron microscopy images.

DOI：
10.1038/s41598-021-87015-2
发表时间：
2021-04-08
期刊：
Scientific reports
影响因子：
4.6
作者：
Jerez D;Stuart E;Schmitt K;Guerrero-Given D;Christie JM;Hahn WE;Kamasawa N;Smirnov MS
通讯作者：
Smirnov MS

Expression of a Form of Cerebellar Motor Memory Requires Learned Alterations to the Activity of Inhibitory Molecular Layer Interneurons.

小脑运动记忆的某种形式的表达需要对抑制分子层中间神经元的活动进行后天的改变。

DOI：
10.1523/jneurosci.0731-22.2022
发表时间：
2023
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Bonnan,Audrey;Zhang,Ke;Gaffield,MichaelA;Christie,JasonM
通讯作者：
Christie,JasonM

Cerebellum encodes and influences the initiation, performance, and termination of discontinuous movements in mice.

DOI：
10.7554/elife.71464
发表时间：
2022-04-22
期刊：
ELIFE
影响因子：
7.7
作者：
Gaffield, Michael A.;Sauerbrei, Britton A.;Christie, Jason M.;Ito-Ishida, Aya
通讯作者：
Ito-Ishida, Aya