Consequences of VGluT3 deficiency on learning and memory in mice

Fazekas, Csilla Lea; Balázsfi, Diána; Horváth, Hanga Réka; Balogh, Zoltán; Aliczki, Manó; Puhova, Agnesa; Balagova, Lucia; Chmelova, Magdalena; Ježová, Daniela; Haller, József; Zelena, Dóra

doi:10.1016/j.physbeh.2019.112688

Cited by 14 publications

(21 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also noted a decrease in cell surface densities of D1R and M1 mAChR, both of which are expressed in VGLUT3 + interneurons and regulate synaptic plasticity mechanisms and memory-processing functions in the hippocampus ( Cea-del Rio et al, 2010 ; Furini et al, 2014 ; Dennis et al, 2016 ; Puighermanal et al, 2017 ). Collectively, these changes in glutamatergic and nonglutamatergic receptor topographies might explain the impaired working memory and cognitive flexibility previously reported in VGLUT3 −/− mice ( Fazekas et al, 2019 ).…”

Section: Discussionmentioning

confidence: 69%

VGLUT3 Ablation Differentially Modulates Glutamate Receptor Densities in Mouse Brain

Ibrahim

Fasano

Abd-Elrahman

et al. 2022

eNeuro

View full text Add to dashboard Cite

Type 3 vesicular glutamate transporter (VGLUT3) represents a unique modulator of glutamate release from both nonglutamatergic and glutamatergic varicosities within the brain. Despite its limited abundance, VGLUT3 is vital for the regulation of glutamate signaling and, therefore, modulates the activity of various brain microcircuits. However, little is known about how glutamate receptors are regulated by VGLUT3 across different brain regions. Here, we used VGLUT3 constitutive knock-out (VGLUT3 –/– ) mice and explored how VGLUT3 deletion influences total and cell surface expression of different ionotropic and metabotropic glutamate receptors. VGLUT3 deletion upregulated the overall expression of metabotropic glutamate receptors mGluR5 and mGluR2/3 in the cerebral cortex. In contrast, no change in the total expression of ionotropic NMDAR glutamate receptors were observed in the cerebral cortex of VGLUT3 –/– mice. We noted significant reduction in cell surface levels of mGluR5, NMDAR2A, NMDAR2B, as well as reductions in dopaminergic D 1 receptors and muscarinic M1 acetylcholine receptors in the hippocampus of VGLUT3 –/– mice. Furthermore, mGluR2/3 total expression and mGluR5 cell surface levels were elevated in the striatum of VGLUT3 –/– mice. Last, AMPAR subunit GluA1 was significantly upregulated throughout cortical, hippocampal, and striatal brain regions of VGLUT3 –/– mice. Together, these findings complement and further support the evidence that VGLUT3 dynamically regulates glutamate receptor densities in several brain regions. These results suggest that VGLUT3 may play an intricate role in shaping glutamatergic signaling and plasticity in several brain areas.

show abstract

Section: Discussionmentioning

confidence: 69%

VGLUT3 Ablation Differentially Modulates Glutamate Receptor Densities in Mouse Brain

Ibrahim

Fasano

Abd-Elrahman

et al. 2022

eNeuro

View full text Add to dashboard Cite

show abstract

“…In a recent report, VGLUT3 knockout mice showed normal learning behavior and intact social and spatial memory. Nevertheless, mild impairments in working memory and cognitive flexibility have been noted, suggesting a deficit in cortico-hippocampal interaction (Fazekas et al, 2019). Overall, the current evidence describes an evident role for both VGLUT3 and mGluR5 signaling in hippocampal networks, yet the impact on memory-processing and learning phenotypes remains dependent, for the most part, on mGluR5 activity.…”

Section: Vglut3-mglur5 Axis In Hippocampal Networkmentioning

confidence: 71%

Targeting Vesicular Glutamate Transporter Machinery: Implications on Metabotropic Glutamate Receptor 5 Signaling and Behavior

Ibrahim¹,

Abd-Elrahman²,

Mestikawy³

et al. 2020

Mol Pharmacol

View full text Add to dashboard Cite

Cross talk between both pre-and postsynaptic components of glutamatergic neurotransmission plays a crucial role in orchestrating a multitude of brain functions, including synaptic plasticity and motor planning. Metabotropic glutamate receptor (mGluR) 5 exhibits promising therapeutic potential for many neurodevelopmental and neurodegenerative disorders as a consequence of its modulatory control over diverse neuronal networks required for memory, motor coordination, neuronal survival, and differentiation. Given these crucial roles, mGluR5 signaling is under the tight control of glutamate release machinery mediated through vesicular glutamate transporters (VGLUTs) that ultimately dictate glutamatergic output. A particular VGLUT isoform, VGLUT3, exhibits an overlapping, but unique, distribution with mGluR5, and the dynamic cross talk between mGluR5 and VGLUT3 is key for the function of specific neuronal networks involved in motor coordination, emotions, and cognition. Thus, aberrant signaling of the VGLUT3-mGluR5 axis is linked to various pathologies including, but not limited to, Parkinson disease, anxiety disorders, and drug addiction. We argue that a comprehensive profiling of how coordinated VGLUT3-mGluR5 signaling influences overall glutamatergic neurotransmission is warranted. SIGNIFICANCE STATEMENTVesicular glutamate receptor (VGLUT) 3 machinery orchestrates glutamate release, and its distribution overlaps with metabotropic glutamate receptor (mGluR) 5 in regional brain circuitries, including striatum, hippocampus, and raphe nucleus. Therefore, VGLUT3-mGluR5 cross talk can significantly influence both physiologic and pathophysiologic glutamatergic neurotransmission. Pathological signaling of the VGLUT3-mGluR5 axis is linked to Parkinson disease, anxiety disorders, and drug addiction. However, it is also predicted to contribute to other motor and cognitive disorders.

show abstract

“…In a recent report, VGLUT3 knockout mice showed normal learning behavior and intact social and spatial memory. Nevertheless, mild impairments in working memory and cognitive flexibility have been noted, suggesting a deficit in cortico-hippocampal interaction (Fazekas et al, 2019). Overall, the current evidence describes an evident role for both VGLUT3 and mGluR5 signaling in hippocampal networks, yet the impact on memory-processing and learning phenotypes remain dependant, for the most part, on mGluR5 activity.…”

Section: Vglut3-mglur5 Axis In Hippocampal Networkmentioning

confidence: 71%

Targeting VGLUT Machinery: Implications on mGluR5 Signaling and Behavior

et al. 2020

View full text Add to dashboard Cite

Crosstalk between both pre-and post-synaptic components of glutamatergic neurotransmission plays a crucial role in orchestrating a multitude of brain functions including synaptic plasticity and motor planning. Metabotropic glutamate receptor 5 (mGluR5) exhibits a promising therapeutic potential for many neurodevelopmental and neurodegenerative disorders, as the consequence of its modulatory control over diverse neuronal networks required for memory, motor coordination, neuronal survival and differentiation. Given these crucial roles, mGluR5 signaling is under the tight control of glutamate release machinery mediated through vesicular glutamate transporters (VGLUTs) to ultimately dictate glutamatergic output. A particular VGLUT isoform, VGLUT3, exhibits an overlapping, but unique, distribution with mGluR5 and the dynamic crosstalk between mGluR5 and VGLUT3 is key for the function of specific neuronal networks involved in motor coordination, emotions and cognition. Thus, aberrant signaling of the VGLUT3/mGluR5 axis is linked to various pathologies including, but not limited to, Parkinson's disease, anxiety disorders and drug addiction. We argue that a comprehensive profiling of how coordinated VGLUT3/mGluR5 signaling influences overall glutamatergic neurotransmission is warranted. Significance statement: Vesicular glutamate receptor 3 (VGLUT3) machinery orchestrates glutamate release and its distribution overlaps with metabotropic glutamate receptor 5 (mGluR5) in regional brain circuitries including striatum, hippocampus and raphe nucleus. Therefore, VGLUT3/mGluR5 crosstalk can significantly influences both physiological and pathophysiological glutamatergic neurotransmission. Pathological signaling of the VGLUT3/mGluR5 axis is linked to Parkinson's disease, anxiety disorders and drug addiction. However, it is also predicted to contribute to other motor and cognitive disorders.

show abstract

Consequences of VGluT3 deficiency on learning and memory in mice

Cited by 14 publications

References 64 publications

VGLUT3 Ablation Differentially Modulates Glutamate Receptor Densities in Mouse Brain

VGLUT3 Ablation Differentially Modulates Glutamate Receptor Densities in Mouse Brain

Targeting Vesicular Glutamate Transporter Machinery: Implications on Metabotropic Glutamate Receptor 5 Signaling and Behavior

Targeting VGLUT Machinery: Implications on mGluR5 Signaling and Behavior

Contact Info

Product

Resources

About