Figures and data in Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation

Version of Record: March 17, 2020

Download
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
- Article PDF
- Figures PDF
Open citations (links to open the citations from this article in various online reference manager services)
- Mendeley
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Amanda M Brown

Joshua J White

Meike E van der Heijden

Joy Zhou

Tao Lin

Roy V Sillitoe

(2020)
Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation

eLife 9:e51928.

https://doi.org/10.7554/eLife.51928
- Download BibTeX
- Download .RIS
Cite
Share
CommentOpen annotations (there are currently 0 annotations on this page).

Figures
Videos
Tables
Additional files

5 figures, 4 videos, 5 tables and 1 additional file

Figures

Figure 1 with 3 supplements

Download asset Open asset

Purkinje cell neurotransmission is necessary for producing baseline physiological tremor and pathological tremor.

(a) Representation of a sagittal section of a mouse cerebellum indicating its spatial relationship to other landmarks of the central nervous system. Green region = Purkinje cell dendrites and …

Figure 1—source data 1 Source data for representative graphs in Figure 1.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig1-data1-v1.xlsx
Download elife-51928-fig1-data1-v1.xlsx

Figure 1—figure supplement 1

Download asset Open asset

Baseline tremor power of both genotypes and power of tremor in recordings of *Pcp2^Cre;Slc32a1^flox/flox* mice after harmaline administration are an order of magnitude smaller than that of *Slc32a1^flox/flox* mice after harmaline administration.

(a) Solid line = mean. Shaded region = standard error of the mean (SEM). Legend on right. This is a magnified view of the data in Figure 1g.

Figure 1—figure supplement 1—source data 1 Precision measures, exact p-values, and replicate data relevant to Figure 1.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig1-figsupp1-data1-v1.docx
Download elife-51928-fig1-figsupp1-data1-v1.docx

Figure 1—figure supplement 2

Download asset Open asset

No difference in tremor was found between males and females.

(**a–b**) Comparison of male and female animals for all tremor conditions tested in Figure 1h–i. Green = male, magenta = female. No significant difference was found between sexes in any condition. *Slc32a…*

Figure 1—figure supplement 2—source data 1 Source data for representative graphs in Figure 1—figure supplement 2.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig1-figsupp2-data1-v1.xlsx
Download elife-51928-fig1-figsupp2-data1-v1.xlsx

Figure 1—figure supplement 3

Download asset Open asset

Mice lacking Purkinje cell GABA neurotransmission have reduced c-Fos expression in response to harmaline administration in the cerebellar nuclei, despite similar levels of activation in the inferior olive.

(a) Quantification of detected c-Fos puncta density in the cerebellar nuclei after harmaline administration. Fastigial: *Slc32a1^flox/flox* n = 16, mean = 0.0003656; *Pcp2^Cre;Slc32a1^flox/flox* n = 14, …

Figure 1—figure supplement 3—source data 1 Source data for representative graphs in Figure 1—figure supplement 3.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig1-figsupp3-data1-v1.xlsx
Download elife-51928-fig1-figsupp3-data1-v1.xlsx

Figure 2

Download asset Open asset

Purkinje cell firing patterns are significantly altered after harmaline administration.

(a) Representation of craniotomy site using skull landmarks. Craniotomy (green circle) for awake head-fixed neural recordings was made −6.4 mm from Bregma (blue arrow) and 1.3 mm lateral from …

Figure 2—source data 1 Source data for representative graphs in Figure 2.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig2-data1-v1.xlsx
Download elife-51928-fig2-data1-v1.xlsx

Figure 3

Download asset Open asset

A burst pattern of cerebellar nuclei activity is associated with the tremor phenotype.

(a) Representation of an extracellular recording of the cerebellar nuclei. (**b–e**) Example raw traces from recordings of cerebellar nuclei cells. Scale = 250 ms. (b) Cerebellar nuclei cell from a …

Figure 3—source data 1 Source data for representative graphs in Figure 3.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig3-data1-v1.xlsx
Download elife-51928-fig3-data1-v1.xlsx

Figure 4 with 3 supplements

Download asset Open asset

The burst pattern of cerebellar nuclei activity is sufficient to produce tremor at multiple frequencies.

(a) Representation of an optical fiber in the cerebellar nuclei. (b) Representation of EMG and optical fiber implant strategy. EMG electrodes are implanted into the gastrocnemius muscle (pink) of …

Figure 4—source data 1 Source data for representative graphs in Figure 4.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig4-data1-v1.xlsx
Download elife-51928-fig4-data1-v1.xlsx

Figure 4—figure supplement 1

Download asset Open asset

Expression of channelrhodopsin is limited to Purkinje cells when reporter expression is driven with a *Pcp2^Cre* allele.

(a) Photomicrograph of a sagittal section of the cerebellum and brainstem from a *Pcp2^Cre;ROSA26^{loxP-STOP-loxP-ChR2-EYFP}* mouse after immunostaining with GFP to enhance the detection of EYFP …

Figure 4—figure supplement 2

Download asset Open asset

Targeting of optic fibers for optogenetic stimulation of Purkinje cell terminals in the cerebellar nuclei.

(a) Dissection of cerebellum within skull. Arrows indicate location of optical fibers penetrating the tissue. Dotted circles indicate the location of the dentate (DN), interposed (IN), and fastigial …

Figure 4—figure supplement 3

Download asset Open asset

Tremor severity increases as optogenetic stimulation light power increases.

(a) Average tremor power for each of the LED light powers tested (solid lines) surrounded by the standard error of the mean (shaded regions). Stimulation always occurred at 10 Hz. (b) Average power …

Figure 4—figure supplement 3—source data 1 Source data for representative graphs in Figure 4—figure supplement 3.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig4-figsupp3-data1-v1.xlsx
Download elife-51928-fig4-figsupp3-data1-v1.xlsx

Figure 5 with 1 supplement

Download asset Open asset

Closed-loop DBS targeted to the interposed nucleus reduces tremor severity.

(a) Picture of the custom-built tremor monitor. (b) Representation of the closed-loop design. Left: a mouse exhibiting tremor behavior shakes the tremor monitor chamber with an attached …

Figure 5—source data 1 Source data for representative graphs in Figure 5.: https://cdn.elifesciences.org/articles/51928/elife-51928-fig5-data1-v1.xlsx
Download elife-51928-fig5-data1-v1.xlsx

Figure 5—figure supplement 1

Download asset Open asset

DBS electrodes targeted to the cerebellar interposed nucleus.

(**a–b**) Sample photomicrographs of Nissl stained neural tissue after removal of the DBS electrodes in two different mice. Arrows indicate the void where DBS electrodes penetrated the tissue. Dotted …

Videos

Video 1

Download asset

posterframe for video — *Pcp2^Cre;Slc32a1^flox/flox* mice exhibit ataxia and disequilibrium, but not pathological tremor.

Video 2

Download asset

Video 3

Download asset

Video 4

Download asset

Tables

Table 1

Precision measures, exact p-values, and replicate data relevant to Figure 1.

Figure	Comparator 1	Comparator 2	Mean 1	Mean 2	SE of diff.	N 1	N 2	Summary	Adjusted P Value
Figure 1h	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.002181 V²	0.02005 V²	0.005132	16	16	*	0.0190
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.002181 V²	0.001438 V²	0.0003786	16	12	ns	0.2982
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.002181 V²	0.002787 V²	0.0007072	16	13	ns	0.9420
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.02005 V²	0.001438 V²	0.005133	16	12	*	0.0142
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.02005 V²	0.002787 V²	0.005168	16	13	*	0.0252
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.001438 V²	0.002787 V²	0.0007151	12	13	ns	0.3550
Figure 1i	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.001032 V²	0.001767 V²	0.0003403	16	16	ns	0.2224
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.001032 V²	0.0005844 V²	0.0001552	16	12	*	0.0454
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.001032 V²	0.0008114 V²	0.0002104	16	13	ns	0.8693
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.001767 V²	0.0005844 V²	0.0003403	16	12	*	0.0155
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.001767 V²	0.0008114 V²	0.0003688	16	13	ns	0.0897
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.0005844 V²	0.0008114 V²	0.0002104	12	13	ns	0.8543

Table 2

Precision measures, exact p-values, and replicate data relevant to Figure 2.

Figure	Comparator 1	Comparator 2	Mean 1	Mean 2	SE of diff.	N 1	N 2	Summary	Adjusted P Value
Figure 2h	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	77.63 Hz	49.18 Hz	7.497	18	14	**	0.0020
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	77.63 Hz	55.97 Hz	7.355	18	15	*	0.0238
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	77.63 Hz	26.65 Hz	7.840	18	12	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	49.18 Hz	55.97 Hz	7.818	14	15	ns	0.8208
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	49.18 Hz	26.65 Hz	8.276	14	12	*	0.0419
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	55.97 Hz	26.65 Hz	8.148	15	12	**	0.0037
Figure 2i	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.4902	1.372	0.2017	18	14	***	0.0003
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.4902	1.152	0.1979	18	15	**	0.0079
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.4902	1.953	0.2109	18	12	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	1.372	1.152	0.2103	14	15	ns	0.7229
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	1.372	1.953	0.2227	14	12	ns	0.0552
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	1.152	1.953	0.2192	15	12	**	0.0032
Figure 2j	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.4443	0.6683	0.05314	18	14	***	0.0005
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.4443	0.5355	0.05214	18	15	ns	0.3088
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.4443	0.8396	0.05558	18	12	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.6683	0.5355	0.05542	14	15	ns	0.0897
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.6683	0.8396	0.05867	14	12	*	0.0253
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.5355	0.8396	0.05776	15	12	****	<0.0001
Figure 2k	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	1.289 Hz	2.876 Hz	0.3641	18	14	***	0.0003
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	1.289 Hz	1.458 Hz	0.3572	18	15	ns	0.9649
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	1.289 Hz	5.338 Hz	0.3807	18	12	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	2.876 Hz	1.458 Hz	0.3797	14	15	**	0.0025
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	2.876 Hz	5.338 Hz	0.4019	14	12	****	<0.0001
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	1.458 Hz	5.338 Hz	0.3957	15	12	****	<0.0001
Figure 2l	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.7396	0.5753	0.07763	18	14	ns	0.1609
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.7396	0.8631	0.07617	18	15	ns	0.3751
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.7396	0.4335	0.08119	18	12	**	0.0022
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.5753	0.8631	0.08096	14	15	**	0.0043
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.5753	0.4335	0.08571	14	12	ns	0.3572
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.8631	0.4335	0.08438	15	12	****	<0.0001
Figure 2m	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.8876	0.5399	0.05937	18	14	****	<0.0001
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.8876	0.9082	0.05824	18	15	ns	0.9848
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.8876	0.3224	0.06209	18	12	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.5399	0.9082	0.06191	14	15	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.5399	0.3224	0.06554	14	12	**	0.0085
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.9082	0.3224	0.06453	15	12	****	<0.0001
Figure 2n	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.008528 s	0.04651 s	0.009766	18	14	**	0.0015
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.008528 s	0.02349 s	0.009581	18	15	ns	0.4089
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.008528 s	0.09622 s	0.01021	18	12	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.04651 s	0.02349 s	0.01018	14	15	ns	0.1202
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.04651 s	0.09622 s	0.01078	14	12	***	0.0001
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.02349 s	0.09622 s	0.01061	15	12	****	<0.0001
Figure 2o	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.01806 s	0.01806 s	0.006551	18	14	ns	>0.9999
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.01806 s	0.03709 s	0.006427	18	15	*	0.0228
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.01806 s	0.02643 s	0.006851	18	12	ns	0.6161
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.01806 s	0.03709 s	0.006831	14	15	*	0.0358
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.01806 s	0.02643 s	0.007232	14	12	ns	0.6560
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.03709 s	0.02643 s	0.007120	15	12	ns	0.4462
Figure 2p	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	59.78	17.71	11.71	18	17	**	0.0035
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	59.78	53.83	11.54	18	18	ns	0.9551
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	59.78	8.421	12.10	18	15	***	0.0004
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	17.71	53.83	11.71	17	18	*	0.0155
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	17.71	8.421	12.26	17	15	ns	0.8730
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	53.83	8.421	12.10	18	15	**	0.0021

Table 3

Precision measures, exact p-values, and replicate data relevant to Figure 3.

Figure	Comparator 1	Comparator 2	Mean 1	Mean 2	SE of diff.	N 1	N 2	Summary	Adjusted P Value
Figure 3f	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	66.48 Hz	74.56 Hz	10.44	19	14	ns	0.8660
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	66.48 Hz	79.81 Hz	9.753	19	18	ns	0.5246
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	66.48 Hz	82.22 Hz	11.23	19	11	ns	0.5035
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	74.56 Hz	79.81 Hz	10.57	14	18	ns	0.9593
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	74.56 Hz	82.22 Hz	11.95	14	11	ns	0.9180
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	79.81 Hz	82.22 Hz	11.35	18	11	ns	0.9966
Figure 3g	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.4511	0.8654	0.08621	19	14	****	<0.0001
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.4511	0.3428	0.08050	19	18	ns	0.5379
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.4511	0.3695	0.09273	19	11	ns	0.8150
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.8654	0.3428	0.08722	14	18	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.8654	0.3695	0.09861	14	11	****	<0.0001
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.3428	0.3695	0.09367	18	11	ns	0.9918
Figure 3h	Slc32a1^flox/flox baseline	Slc32a1^flox/flox + harmaline	0.4141	0.5262	0.04266	19	14	ns	0.0520
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.4141	0.2310	0.03984	19	18	***	0.0001
	Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.4141	0.2743	0.04589	19	11	*	0.0179
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox baseline	0.5262	0.2310	0.04316	14	18	****	<0.0001
	Slc32a1^flox/flox + harmaline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.5262	0.2743	0.04880	14	11	****	<0.0001
	Pcp2^Cre;Slc32a1^flox/flox baseline	Pcp2^Cre;Slc32a1^flox/flox + harmaline	0.2310	0.2743	0.04636	18	11	ns	0.7864

Table 4

Precision measures, exact p-values, and replicate data relevant to Figure 4.

Figure	Comparator 1	Comparator 2	Mean 1	Mean 2	SE of diff.	N 1	N 2	Summary	Adjusted P Value
Figure 4n	pre	during	0.1825	1.000	0.05238	7	7	****	<0.0001
	pre	post	0.1825	0.1702	0.06337	7	7	ns	0.9796
	during	post	1.000	0.1702	0.08224	7	7	***	0.0001

Table 5

Precision measures, exact p-values, and replicate data relevant to Figure 5.

Figure	Comparator 1	Comparator 2	Mean 1	Mean 2	SE of diff.	N 1	N 2	Summary	Adjusted P Value
Figure 5i	baseline	harmaline	0.09208	1.000	0.03831	8	8	****	<0.0001
	baseline	closed-loop DBS + harmaline	0.09208	0.2129	0.07930	8	8	ns	0.3375
	harmaline	closed-loop DBS + harmaline	1.000	0.2129	0.06191	8	8	****	<0.0001

Additional files

Transparent reporting form: https://cdn.elifesciences.org/articles/51928/elife-51928-transrepform-v1.pdf
Download elife-51928-transrepform-v1.pdf

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

Figures

Purkinje cell neurotransmission is necessary for producing baseline physiological tremor and pathological tremor.

Figure 1—source data 1

Baseline tremor power of both genotypes and power of tremor in recordings of Pcp2^Cre;Slc32a1^flox/flox mice after harmaline administration are an order of magnitude smaller than that of Slc32a1^flox/flox mice after harmaline administration.

Figure 1—figure supplement 1—source data 1

No difference in tremor was found between males and females.

Figure 1—figure supplement 2—source data 1

Mice lacking Purkinje cell GABA neurotransmission have reduced c-Fos expression in response to harmaline administration in the cerebellar nuclei, despite similar levels of activation in the inferior olive.

Figure 1—figure supplement 3—source data 1

Purkinje cell firing patterns are significantly altered after harmaline administration.

Figure 2—source data 1

A burst pattern of cerebellar nuclei activity is associated with the tremor phenotype.

Figure 3—source data 1

The burst pattern of cerebellar nuclei activity is sufficient to produce tremor at multiple frequencies.

Figure 4—source data 1

Expression of channelrhodopsin is limited to Purkinje cells when reporter expression is driven with a Pcp2^Cre allele.

Targeting of optic fibers for optogenetic stimulation of Purkinje cell terminals in the cerebellar nuclei.

Tremor severity increases as optogenetic stimulation light power increases.

Figure 4—figure supplement 3—source data 1

Closed-loop DBS targeted to the interposed nucleus reduces tremor severity.

Figure 5—source data 1

DBS electrodes targeted to the cerebellar interposed nucleus.

Videos

Pcp2^Cre;Slc32a1^flox/flox mice exhibit ataxia and disequilibrium, but not pathological tremor.

Harmaline induces a severe tremor in Slc32a1^flox/flox mice but not in Pcp2^Cre;Slc32a1^flox/flox mice.

Optogenetic stimulation of Purkinje cell terminals in the interposed nuclei of Pcp2^Cre;ROSA26^{loxP-STOP-loxP-ChR2-EYFP} mice using a 10 Hz sinusoidal stimulus induces a robust tremor.

Closed-loop DBS of the interposed nucleus reduces harmaline-induced tremor.

Tables

Precision measures, exact p-values, and replicate data relevant to Figure 1.

Precision measures, exact p-values, and replicate data relevant to Figure 2.

Precision measures, exact p-values, and replicate data relevant to Figure 3.

Precision measures, exact p-values, and replicate data relevant to Figure 4.

Precision measures, exact p-values, and replicate data relevant to Figure 5.

Additional files

Transparent reporting form

Download links

Be the first to read new articles from eLife

Share this article

Cite this article

Purkinje cell neurotransmission is necessary for producing baseline physiological tremor and pathological tremor.

Figure 1—source data 1

Baseline tremor power of both genotypes and power of tremor in recordings of Pcp2Cre;Slc32a1flox/flox mice after harmaline administration are an order of magnitude smaller than that of Slc32a1flox/flox mice after harmaline administration.

Figure 1—figure supplement 1—source data 1

No difference in tremor was found between males and females.

Figure 1—figure supplement 2—source data 1

Mice lacking Purkinje cell GABA neurotransmission have reduced c-Fos expression in response to harmaline administration in the cerebellar nuclei, despite similar levels of activation in the inferior olive.

Figure 1—figure supplement 3—source data 1

Purkinje cell firing patterns are significantly altered after harmaline administration.

Figure 2—source data 1

A burst pattern of cerebellar nuclei activity is associated with the tremor phenotype.

Figure 3—source data 1

The burst pattern of cerebellar nuclei activity is sufficient to produce tremor at multiple frequencies.

Figure 4—source data 1

Expression of channelrhodopsin is limited to Purkinje cells when reporter expression is driven with a Pcp2Cre allele.

Targeting of optic fibers for optogenetic stimulation of Purkinje cell terminals in the cerebellar nuclei.

Tremor severity increases as optogenetic stimulation light power increases.

Figure 4—figure supplement 3—source data 1

Closed-loop DBS targeted to the interposed nucleus reduces tremor severity.

Figure 5—source data 1

DBS electrodes targeted to the cerebellar interposed nucleus.

Pcp2Cre;Slc32a1flox/flox mice exhibit ataxia and disequilibrium, but not pathological tremor.

Harmaline induces a severe tremor in Slc32a1flox/flox mice but not in Pcp2Cre;Slc32a1flox/flox mice.

Optogenetic stimulation of Purkinje cell terminals in the interposed nuclei of Pcp2Cre;ROSA26loxP-STOP-loxP-ChR2-EYFP mice using a 10 Hz sinusoidal stimulus induces a robust tremor.

Closed-loop DBS of the interposed nucleus reduces harmaline-induced tremor.

Precision measures, exact p-values, and replicate data relevant to Figure 1.

Precision measures, exact p-values, and replicate data relevant to Figure 2.

Precision measures, exact p-values, and replicate data relevant to Figure 3.

Precision measures, exact p-values, and replicate data relevant to Figure 4.

Precision measures, exact p-values, and replicate data relevant to Figure 5.

Transparent reporting form

Baseline tremor power of both genotypes and power of tremor in recordings of Pcp2^Cre;Slc32a1^flox/flox mice after harmaline administration are an order of magnitude smaller than that of Slc32a1^flox/flox mice after harmaline administration.

Expression of channelrhodopsin is limited to Purkinje cells when reporter expression is driven with a Pcp2^Cre allele.

Pcp2^Cre;Slc32a1^flox/flox mice exhibit ataxia and disequilibrium, but not pathological tremor.

Harmaline induces a severe tremor in Slc32a1^flox/flox mice but not in Pcp2^Cre;Slc32a1^flox/flox mice.

Optogenetic stimulation of Purkinje cell terminals in the interposed nuclei of Pcp2^Cre;ROSA26^{loxP-STOP-loxP-ChR2-EYFP} mice using a 10 Hz sinusoidal stimulus induces a robust tremor.