Enhanced innate fear and altered stress axis regulation in VGluT3 knockout mice

Balázsfi, Diána; Fodor, Anna; Török, Bibiána; Ferenczi, Szilamér; Kovács, Krisztina; Haller, József; Zelena, Dóra

doi:10.1080/10253890.2017.1423053

Cited by 23 publications

(27 citation statements)

References 55 publications

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“…But to date, optogenetic experiments convincingly established that glutamate cotransmission regulates reward-related behaviors (Birgner et al, 2010; Hnasko et al, 2010; Witten et al, 2010; Adamantidis et al, 2011; Alsiö et al, 2011; Liu et al, 2014) and auditory or respiratory functions (Abbott et al, 2014; Burke et al, 2014). The implication of glutamate cotransmission in other brain functions such as memory, fear or stress is not clearly established (Balázsfi et al, 2018).…”

Section: Introduction On Cotransmission and The Discovery Of Vglutsmentioning

confidence: 99%

Glutamate Cotransmission in Cholinergic, GABAergic and Monoamine Systems: Contrasts and Commonalities

Trudeau¹,

Mestikawy²

2018

Front. Neural Circuits

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Multiple discoveries made since the identification of vesicular glutamate transporters (VGLUTs) two decades ago revealed that many neuronal populations in the brain use glutamate in addition to their “primary” neurotransmitter. Such a mode of cotransmission has been detected in dopamine (DA), acetylcholine (ACh), serotonin (5-HT), norepinephrine (NE) and surprisingly even in GABA neurons. Interestingly, work performed by multiple groups during the past decade suggests that the use of glutamate as a cotransmitter takes different forms in these different populations of neurons. In the present review, we will provide an overview of glutamate cotransmission in these different classes of neurons, highlighting puzzling differences in: (1) the proportion of such neurons expressing a VGLUT in different brain regions and at different stages of development; (2) the sub-cellular localization of the VGLUT; (3) the localization of the VGLUT in relation to the neurons’ other vesicular transporter; and (4) the functional role of glutamate cotransmission.

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Section: Introduction On Cotransmission and The Discovery Of Vglutsmentioning

confidence: 99%

Glutamate Cotransmission in Cholinergic, GABAergic and Monoamine Systems: Contrasts and Commonalities

Trudeau¹,

Mestikawy²

2018

Front. Neural Circuits

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“…Although our results suggest that 5-HT and glutamate are co-released in the ventral and dorsal striatum where DARPP-32 is likely recruited following exposure to drugs of abuse, further studies are required to determine the precise role played by 5-HT and/or glutamate and their different receptors in DARPP-32 activation, the subsequent neuroplastic changes and the cognitive/emotional deficits produced by drugs of abuse. Furthermore, genetic ablation of VGLUT3 in mice (vglut3-/-) produces increased anxiety (Amilhon et al, 2010; Sakae et al, 2018), enhanced fear and altered stress axis regulation (Balázsfi et al, 2018), concomitant to the desensitization of 5-HT1A autoreceptors (Amilhon et al, 2010), suggesting a potential cross-regulation between 5-HT1A receptors and glutamate co-release. In line with this, unpublished evidence from our laboratory suggests that chronic treatment with drugs targeting the 5-HT1A receptors alter the density of 5-HT/VGLUT3 varicosities in specific brain region, including the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Axonal Non-segregation of the Vesicular Glutamate Transporter VGLUT3 Within Serotonergic Projections in the Mouse Forebrain

Belmer

Beecher

Jacques

et al. 2019

Front. Cell. Neurosci.

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A subpopulation of raphe 5-HT neurons expresses the vesicular glutamate transporter VGLUT3 with the co-release of glutamate and serotonin proposed to play a pivotal role in encoding reward- and anxiety-related behaviors. Serotonin axons are identifiable by immunolabeling of either serotonin (5-HT) or the plasma membrane 5-HT transporter (SERT), with SERT labeling demonstrated to be only partially overlapping with 5-HT staining. Studies investigating the colocalization or segregation of VGLUT3 within SERT or 5-HT immunolabeled boutons have led to inconsistent results. Therefore, we combined immunohistochemistry, high resolution confocal imaging, and 3D-reconstruction techniques to map and quantify the distribution of VGLUT3 immunoreactive boutons within 5-HT vs. SERT-positive axons in various regions of the mouse forebrain, including the prefrontal cortex, nucleus accumbens core and shell, bed nucleus of the stria terminalis, dorsal striatum, lateral septum, basolateral and central amygdala, and hippocampus. Our results demonstrate that about 90% of 5-HT boutons are colocalized with SERT in almost all the brain regions studied, which therefore reveals that VGLUT3 and SERT do not segregate. However, in the posterior part of the NAC shell, we confirmed the presence of a subtype of 5-HT immunoreactive axons that lack the SERT. Interestingly, about 90% of the 5-HT/VGLUT3 boutons were labeled for the SERT in this region, suggesting that VGLUT3 is preferentially located in SERT immunoreactive 5-HT boutons. This work demonstrates that VGLUT3 and SERT cannot be used as specific markers to classify the different subtypes of 5-HT axons.

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“…In fact, VGLUT3 −/− mice that are hyperactive when placed in normal housing conditions, turn out to be hypoactive when exposed to stressful environments. 9,43,44 Within each strain, VGLUT3 expression varies substantially according to the brain region involved in anxiety-and drug-related behavior. Between strains, the overall VGLUT3 expression is also different, with C3H/HeH = 129/Sv, C57Bl/6N and BALB/c = DBA/2, from the highest VGLUT3 expression to the lowest, respectively.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of VGLUT3 in laboratory mouse strains: Impact on drug‐induced hyperlocomotion and anxiety‐related behaviors

Sakae

Ramet

Henrion

et al. 2018

Genes Brain and Behavior

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The atypical vesicular glutamate transporter VGLUT3 is present in subpopulations of GABAergic interneurons in the cortex and the hippocampus, in subgroups of serotoninergic neurons in raphe nuclei, and in cholinergic interneurons in the striatum. C56BL/6N mice that no longer express VGLUT3 (VGLUT3−/−) display anxiety‐associated phenotype, increased spontaneous and cocaine‐induced locomotor activity and decreased haloperidol‐induced catalepsy. Inbred mouse strains differ markedly in their sensitivity to anxiety and behavioral responses elicited by drugs. The purpose of this study was to investigate strain differences in VGLUT3 expression levels and its potential correlates with anxiety and reward‐guided behaviors. Five inbred mouse lines were chosen according to their contrasted anxiety and drugs sensitivity: C57BL/6N, C3H/HeN, DBA/2J, 129/Sv, and BALB/c. VGLUT3 protein expression was measured in different brain areas involved in reward or mood regulation (such as the striatum, the hippocampus, and raphe nuclei) and genetic variations in Slc17a8, the gene encoding for VGLUT3, have been explored. These five inbred mouse strains express very different levels of VGLUT3, which cannot be attributed to the genetic variation of the Slc17a8 locus. Furthermore, mice behavior in the open field, elevated plus maze, spontaneous‐ and cocaine‐induced locomotor was highly heterogeneous and only partially correlated to VGLUT3 levels. These data highlight the fact that one single gene polymorphism could not account for VGLUT3 expression variations, and that region specific VGLUT3 expression level variations might play a key role in the modulation of discrete behaviors.

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Enhanced innate fear and altered stress axis regulation in VGluT3 knockout mice

Cited by 23 publications

References 55 publications

Glutamate Cotransmission in Cholinergic, GABAergic and Monoamine Systems: Contrasts and Commonalities

Glutamate Cotransmission in Cholinergic, GABAergic and Monoamine Systems: Contrasts and Commonalities

Axonal Non-segregation of the Vesicular Glutamate Transporter VGLUT3 Within Serotonergic Projections in the Mouse Forebrain

Differential expression of VGLUT3 in laboratory mouse strains: Impact on drug‐induced hyperlocomotion and anxiety‐related behaviors

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