Vesicular glutamate transporter isoforms: The essential players in the somatosensory systems

Zhang, Fuxing; Ge, Shunnan; Dong, Yu-Lin; Shi, Juan; Feng, Yixuan; Li, Yang; Li, Yunqing; Li, Jinlian

doi:10.1016/j.pneurobio.2018.09.006

Cited by 41 publications

(36 citation statements)

References 233 publications

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“…A future challenge is to manipulate the trigeminal neurons projecting to the cerebellum without affecting those projecting to the thalamus. This may be possible, in principle, as those neurons may be different populations in the trigeminal nuclei 64,65 . On a related note, we do not know whether the early phase inputs to the cerebellar GCL, including the second peak in awake mice, were monosynaptic or polysynaptic.…”

Section: Discussionmentioning

confidence: 99%

Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

2020

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The cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. Even a single tactile stimulus can activate both of these pathways. Here we report how these different types of signals are integrated in the cerebellar cortex. We used in vivo whole-cell recordings from granule cells and unit recordings from Purkinje cells in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of 8 ms and 29 ms), for which only the late phase was S1 dependent. In Purkinje cells, complex spikes and the late phase of simple spikes were S1 dependent. These results indicate that individual granule cells combine convergent inputs from the periphery and neocortex and send their outputs to Purkinje cells, which then integrate those signals with climbing fiber signals from the neocortex.

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Section: Discussionmentioning

confidence: 99%

Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

2020

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“…Several of these molecules have not before been associated with a proprioceptor identity ( Hspe, Colq, Chad, Agpta4 ), while other markers have typically been observed in sensory neurons other than proprioceptors (e.g. vGlut2, Tac1 ) (Zhang et al, 2018; Lallemend and Ernfors, 2012). Especially the latter observation suggests that identification of sensory neuron subtypes on the basis of one or two molecular markers is an unreliable strategy, and similar as observed for other neuronal classes, requires ‘multi-transcript authentication’ (Bikoff et al, 2106; Tasic et al, 2018, Shresta et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Molecular development of muscle spindle and Golgi tendon organ sensory afferents revealed by single proprioceptor transcriptome analysis

Oliver

Florez-Paz

Badea

et al. 2020

Preprint

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Anatomical and physiological analyses have long revealed differences between proprioceptive groups Ia, II, and Ib sensory neurons, yet the molecular correlates of these three muscle afferent subtypes remain unknown. We performed single cell RNA sequencing of genetically identified adult proprioceptors and, using unbiased bioinformatics approaches, detected five molecularly distinct neuronal clusters. Validation of cluster-specific transcripts in dorsal root ganglia (DRG) and skeletal muscle provides evidence these clusters correspond to functionally distinct muscle spindle (MS) or Golgi tendon organ (GTO) afferent proprioceptors. Remarkably, while we uncovered just one type of GTO afferents, four of the five clusters represent MS afferents, thus demonstrating a previously unappreciated diversity among these muscle proprioceptors. In vitro electrophysiological recordings reveal just two broadly distinct proprioceptor types, and suggest that the refinement of functional subtype diversity may occur along multiple axes of maturation. Lineage analysis between proprioceptor transcriptomes at different developmental stages show little or no correlation for transcripts that define adult MS or GTO afferents, supporting the idea that proprioceptor subtype identity emerges late in development. Together, our data provide the first comprehensive molecular signature for groups Ia and II MS afferents and group Ib GTO afferents, and offer new strategies for genetic interrogation of the role of these individual proprioceptor subtypes in regulating voluntary motor behavior.

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“…Previous studies have established that VGLUT including subtype 1, 2, and 3 are expressed in distinct populations of glutamatergic neurons and play multiple roles in the central nervous system [3]. However, VGLUT2, but not VGLUT1 and 3, plays a key role in mediating pain hypersensitivity induced by inflammation and peripheral nerve injury [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…e coexpression of VGLUT2 and two main nociceptors of calcitonin gene-related peptide (CGRP) and transient receptor potential channel (TRPV1) was observed in small-and medium-sized neurons of the dorsal root ganglion (DRG) in mice [4][5][6][7][8]. Additionally, VGLUT2 knock-out mice challenged with CFA demonstrates a complete loss of heat hyperalgesia, whereas mechanical hypersensitivity induced by CFA remains intact.…”

Section: Introductionmentioning

confidence: 99%

VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant

Tang

Peng

Tao

et al. 2020

Pain Research and Management

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Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund’s adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.

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Vesicular glutamate transporter isoforms: The essential players in the somatosensory systems

Cited by 41 publications

References 233 publications

Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

Molecular development of muscle spindle and Golgi tendon organ sensory afferents revealed by single proprioceptor transcriptome analysis

VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant

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