Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

Josef Turecek; Skyler L. Jackman; Wade G. Regehr

doi:10.1016/j.celrep.2016.11.081

Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

Josef Turecek, Skyler L. Jackman, Wade G. Regehr

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABA_A-receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission.

Original language	English (US)
Pages (from-to)	3256-3268
Number of pages	13
Journal	Cell Reports
Volume	17
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2016.11.081
State	Published - Dec 20 2016
Externally published	Yes

Keywords

Purkinje cells
TPMPA
cerebellum
deep cerebellar nucleus
presynaptic
receptor saturation
recovery from depression
short-term facilitation

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2016.11.081

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title = "Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex",

abstract = "The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABAA-receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission.",

keywords = "Purkinje cells, TPMPA, cerebellum, deep cerebellar nucleus, presynaptic, receptor saturation, recovery from depression, short-term facilitation",

author = "Josef Turecek and Jackman, {Skyler L.} and Regehr, {Wade G.}",

note = "Funding Information: This work was supported by NIH grants R01NS032405, R35NS097284, and R01NS092707 and by the Nancy Lurie Marks Foundation, Goldenson Fund, Lefler Center, and Khodadad Foundation (W.G.R.). We thank Shogo Ohmae and Javier F. Medina for providing recordings of Purkinje cell firing in vivo during a conditioned eyeblink task from their paper (Ohmae and Medina, 2015). We also thank the W.G.R. lab for comments on the manuscript. Publisher Copyright: {\textcopyright} 2016 The Author(s)",

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doi = "10.1016/j.celrep.2016.11.081",

language = "English (US)",

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AU - Jackman, Skyler L.

AU - Regehr, Wade G.

N1 - Funding Information: This work was supported by NIH grants R01NS032405, R35NS097284, and R01NS092707 and by the Nancy Lurie Marks Foundation, Goldenson Fund, Lefler Center, and Khodadad Foundation (W.G.R.). We thank Shogo Ohmae and Javier F. Medina for providing recordings of Purkinje cell firing in vivo during a conditioned eyeblink task from their paper (Ohmae and Medina, 2015). We also thank the W.G.R. lab for comments on the manuscript. Publisher Copyright: © 2016 The Author(s)

PY - 2016/12/20

Y1 - 2016/12/20

N2 - The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABAA-receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission. We propose that PC-DCN synapses have two components of release: one prominent early in trains and another specialized to maintain transmission during prolonged activation. Short-term facilitation offsets partial vesicle depletion to produce frequency-independent transmission.

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KW - Purkinje cells

KW - TPMPA

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KW - deep cerebellar nucleus

KW - presynaptic

KW - receptor saturation

KW - recovery from depression

KW - short-term facilitation

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Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex

Abstract

Keywords

ASJC Scopus subject areas

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