TY - JOUR
T1 - Graded coexpression of ion channel, neurofilament, and synaptic genes in fast-spiking vestibular nucleus neurons
AU - Kodama, Takashi
AU - Gittis, Aryn H.
AU - Shin, Minyoung
AU - Kelleher, Keith
AU - Kolkman, Kristine E.
AU - McElvain, Lauren
AU - Lam, Minh
AU - Du Lac, Sascha
N1 - Funding Information:
Received June 26, 2019; revised Oct. 11, 2019; accepted Oct. 25, 2019. Author contributions: T.K., A.H.G., and S.d.L. designed research; A.H.G., M.S., K.K., K.E.K., L.M., and M.L. performed research; T.K., A.H.G., M.S., K.K., K.E.K., L.M., and S.d.L. analyzed data; T.K. and S.d.L. wrote the paper. This work was supported by NIH Grant EY11027 and HHMI. The authors declare no competing financial interests. Correspondence should be addressed to Takashi Kodama at takashi@jhmi.edu or Sascha du Lac at sascha@jhmi.edu. https://doi.org/10.1523/JNEUROSCI.1500-19.2019 Copyright © 2020 the authors
Publisher Copyright:
Copyright © 2020 the authors.
PY - 2020/1/15
Y1 - 2020/1/15
N2 - Computations that require speed and temporal precision are implemented throughout the nervous system by neurons capable of firing at very high rates, rapidly encoding and transmitting a rich amount of information, but with substantial metabolic and physical costs. For economical fast spiking and high throughput information processing, neurons need to optimize multiple biophysical properties in parallel, but the mechanisms of this coordination remain unknown.Wehypothesized that coordinated gene expression may underlie the coordinated tuning of the biophysical properties required for rapid firing and signal transmission. Taking advantage of the diversity of fast-spiking cell types in the medial vestibular nucleus of mice of both sexes, we examined the relationship between gene expression, ionic currents, and neuronal firing capacity. Across excitatory and inhibitory cell types, genes encoding voltage-gated ion channels responsible for depolarizing and repolarizing the action potential were tightly coexpressed, and their absolute expression levels increased with maximal firing rate. Remarkably, this coordinated gene expression extended to neurofilaments and specific presynaptic molecules, providing a mechanism for coregulating axon caliber and transmitter release to match firing capacity. These findings suggest the presence of a module of genes, which is coexpressed in a graded manner and jointly tunes multiple biophysical properties for economical differentiation of firing capacity. The graded tuning of fast-spiking capacity by the absolute expression levels of specific ion channels provides a counterexample to the widely held assumption that cell-type-specific firing patterns can be achieved via a vast combination of different ion channels.
AB - Computations that require speed and temporal precision are implemented throughout the nervous system by neurons capable of firing at very high rates, rapidly encoding and transmitting a rich amount of information, but with substantial metabolic and physical costs. For economical fast spiking and high throughput information processing, neurons need to optimize multiple biophysical properties in parallel, but the mechanisms of this coordination remain unknown.Wehypothesized that coordinated gene expression may underlie the coordinated tuning of the biophysical properties required for rapid firing and signal transmission. Taking advantage of the diversity of fast-spiking cell types in the medial vestibular nucleus of mice of both sexes, we examined the relationship between gene expression, ionic currents, and neuronal firing capacity. Across excitatory and inhibitory cell types, genes encoding voltage-gated ion channels responsible for depolarizing and repolarizing the action potential were tightly coexpressed, and their absolute expression levels increased with maximal firing rate. Remarkably, this coordinated gene expression extended to neurofilaments and specific presynaptic molecules, providing a mechanism for coregulating axon caliber and transmitter release to match firing capacity. These findings suggest the presence of a module of genes, which is coexpressed in a graded manner and jointly tunes multiple biophysical properties for economical differentiation of firing capacity. The graded tuning of fast-spiking capacity by the absolute expression levels of specific ion channels provides a counterexample to the widely held assumption that cell-type-specific firing patterns can be achieved via a vast combination of different ion channels.
KW - Flocculus
KW - High-frequency firing
KW - Ion channel genes
KW - Kv3
KW - Pre-cerebellar
KW - Sodium channel
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U2 - 10.1523/JNEUROSCI.1500-19.2019
DO - 10.1523/JNEUROSCI.1500-19.2019
M3 - Article
C2 - 31719168
AN - SCOPUS:85077953130
SN - 0270-6474
VL - 40
SP - 496
EP - 508
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 3
ER -