Cerebellar modules operate at different frequencies
- Erasmus MC, Netherlands
- Netherlands Institute for Neuroscience, Netherlands
Abstract
Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. Here we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depends on activation of TRPC3, and that this property is relevant for all cerebellar functions.
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Author details
Ethics
Animal experimentation: The experiments performed in this study were approved by the local animal ethical committee ("Dier Experimenten Commissie", DEC).
Reviewing Editor
- Dora E Angelaki, Baylor College of Medicine, United States
Publication history
- Received: February 13, 2014
- Accepted: May 3, 2014
- Accepted Manuscript published: May 7, 2014 (version 1)
- Version of Record published: June 10, 2014 (version 2)
Copyright
© 2014, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Cerebellar modules operate at different frequencies
eLife 3:e02536.
https://doi.org/10.7554/eLife.02536
Further reading
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- Neuroscience
Although the wiring of the cerebellar cortex appears to be uniform, the neurons in this region of the brain behave more differently from each other than previously thought.
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- Neuroscience
TRPV1, a capsaicin- and heat-activated ion channel, is expressed by peripheral nociceptors and has been implicated in various inflammatory and neuropathic pain conditions. Although pharmacological modulation of TRPV1 has attracted therapeutic interest, many TRPV1 agonists and antagonists produce thermomodulatory side effects in animal models and human clinical trials, limiting their utility. These on-target effects may result from the perturbation of TRPV1 receptors on nociceptors, which transduce signals to central thermoregulatory circuits and release proinflammatory factors from their peripheral terminals, most notably the potent vasodilative neuropeptide, calcitonin gene-related peptide (CGRP). Alternatively, these body temperature effects may originate from the modulation of TRPV1 on vascular smooth muscle cells (vSMCs), where channel activation promotes arteriole constriction. Here, we ask which of these pathways is most responsible for the body temperature perturbations elicited by TRPV1 drugs in vivo. We address this question by selectively eliminating TRPV1 expression in sensory neurons or vSMCs and show that only the former abrogates agonist-induced hypothermia and antagonist-induced hyperthermia. Furthermore, lesioning the central projections of TRPV1-positive sensory nerve fibers also abrogates drug-mediated thermomodulation, whereas eliminating CGRP has no effect. Thus, TRPV1 drugs alter core body temperature by modulating sensory input to the central nervous system, rather than through peripheral actions on the vasculature. These findings suggest how mechanistically distinct TRPV1 antagonists may diminish inflammatory pain without affecting core body temperature.
