Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice

IntroductionGlutamate represents the dominant neurotransmitter that conveys the light information to the brain, including the suprachiasmatic nucleus (SCN), the central pacemaker for the circadian system. The neuronal and astrocytic glutamate transporters are crucial for maintaining efficient glutam...

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Main Authors: Hüseyin Korkmaz, Max Anstötz, Tim Wellinghof, Benedetta Fazari, Angelika Hallenberger, Ann Kathrin Bergmann, Elena Niggetiedt, Fatma Delâl Güven, Federica Tundo-Lavalle, Fathima Faiba A. Purath, Kevin Bochinsky, Lothar Gremer, Dieter Willbold, Charlotte von Gall, Amira A. H. Ali
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Cellular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2025.1538985/full
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author Hüseyin Korkmaz
Max Anstötz
Tim Wellinghof
Benedetta Fazari
Angelika Hallenberger
Ann Kathrin Bergmann
Elena Niggetiedt
Fatma Delâl Güven
Federica Tundo-Lavalle
Fathima Faiba A. Purath
Kevin Bochinsky
Lothar Gremer
Lothar Gremer
Dieter Willbold
Dieter Willbold
Charlotte von Gall
Amira A. H. Ali
Amira A. H. Ali
author_facet Hüseyin Korkmaz
Max Anstötz
Tim Wellinghof
Benedetta Fazari
Angelika Hallenberger
Ann Kathrin Bergmann
Elena Niggetiedt
Fatma Delâl Güven
Federica Tundo-Lavalle
Fathima Faiba A. Purath
Kevin Bochinsky
Lothar Gremer
Lothar Gremer
Dieter Willbold
Dieter Willbold
Charlotte von Gall
Amira A. H. Ali
Amira A. H. Ali
author_sort Hüseyin Korkmaz
collection DOAJ
description IntroductionGlutamate represents the dominant neurotransmitter that conveys the light information to the brain, including the suprachiasmatic nucleus (SCN), the central pacemaker for the circadian system. The neuronal and astrocytic glutamate transporters are crucial for maintaining efficient glutamatergic signaling. In the SCN, glutamatergic nerve terminals from the retina terminate on vasoactive intestinal polypeptide (VIP) neurons, which are essential for circadian functions. To date, little is known about the role of the core circadian clock gene, Bmal1, in glutamatergic neurotransmission of light signal to various brain regions.MethodsThe aim of this study was to further elucidate the role of Bmal1 in glutamatergic neurotransmission from the retina to the SCN. We therefore examined the spontaneous rhythmic locomotor activity, neuronal and glial glutamate transporters, as well as the ultrastructure of the synapse between the retinal ganglion cells (RGCs) and the SCN in adult male Bmal1−/− mice.ResultsWe found that the deletion of Bmal1 affects the light-mediated behavior in mice, decreases the retinal thickness and affects the vesicular glutamate transporters (vGLUT1, 2) in the retina. Within the SCN, the immunoreaction of vGLUT1, 2, glial glutamate transporters (GLAST) and VIP was decreased while the glutamate concentration was elevated. At the ultrastructure level, the presynaptic terminals were enlarged and the distance between the synaptic vesicles and the synaptic cleft was increased, indicative of a decrease in the readily releasable pool at the excitatory synapses in Bmal1−/−.ConclusionOur data suggests that Bmal1 deletion affects the glutamate transmission in the retina and the SCN and affects the behavioral responses to light.
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spelling doaj-art-e365c1979ced4f2f907a7dc6042a847b2025-08-20T02:45:24ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022025-02-011910.3389/fncel.2025.15389851538985Loss of Bmal1 impairs the glutamatergic light input to the SCN in miceHüseyin Korkmaz0Max Anstötz1Tim Wellinghof2Benedetta Fazari3Angelika Hallenberger4Ann Kathrin Bergmann5Elena Niggetiedt6Fatma Delâl Güven7Federica Tundo-Lavalle8Fathima Faiba A. Purath9Kevin Bochinsky10Lothar Gremer11Lothar Gremer12Dieter Willbold13Dieter Willbold14Charlotte von Gall15Amira A. H. Ali16Amira A. H. Ali17Faculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyCore Facility for Electron Microscopy, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyJülich Research Center, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Jülich, GermanyJülich Research Center, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Jülich, GermanyInstitute of Physical Biology, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, GermanyJülich Research Center, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Jülich, GermanyInstitute of Physical Biology, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyFaculty of Medicine, Institute of Anatomy II, Heinrich Heine University, Düsseldorf, GermanyDepartment of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, EgyptIntroductionGlutamate represents the dominant neurotransmitter that conveys the light information to the brain, including the suprachiasmatic nucleus (SCN), the central pacemaker for the circadian system. The neuronal and astrocytic glutamate transporters are crucial for maintaining efficient glutamatergic signaling. In the SCN, glutamatergic nerve terminals from the retina terminate on vasoactive intestinal polypeptide (VIP) neurons, which are essential for circadian functions. To date, little is known about the role of the core circadian clock gene, Bmal1, in glutamatergic neurotransmission of light signal to various brain regions.MethodsThe aim of this study was to further elucidate the role of Bmal1 in glutamatergic neurotransmission from the retina to the SCN. We therefore examined the spontaneous rhythmic locomotor activity, neuronal and glial glutamate transporters, as well as the ultrastructure of the synapse between the retinal ganglion cells (RGCs) and the SCN in adult male Bmal1−/− mice.ResultsWe found that the deletion of Bmal1 affects the light-mediated behavior in mice, decreases the retinal thickness and affects the vesicular glutamate transporters (vGLUT1, 2) in the retina. Within the SCN, the immunoreaction of vGLUT1, 2, glial glutamate transporters (GLAST) and VIP was decreased while the glutamate concentration was elevated. At the ultrastructure level, the presynaptic terminals were enlarged and the distance between the synaptic vesicles and the synaptic cleft was increased, indicative of a decrease in the readily releasable pool at the excitatory synapses in Bmal1−/−.ConclusionOur data suggests that Bmal1 deletion affects the glutamate transmission in the retina and the SCN and affects the behavioral responses to light.https://www.frontiersin.org/articles/10.3389/fncel.2025.1538985/fullBmal1circadian systemSCNvGLUTGLASTVIP
spellingShingle Hüseyin Korkmaz
Max Anstötz
Tim Wellinghof
Benedetta Fazari
Angelika Hallenberger
Ann Kathrin Bergmann
Elena Niggetiedt
Fatma Delâl Güven
Federica Tundo-Lavalle
Fathima Faiba A. Purath
Kevin Bochinsky
Lothar Gremer
Lothar Gremer
Dieter Willbold
Dieter Willbold
Charlotte von Gall
Amira A. H. Ali
Amira A. H. Ali
Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
Frontiers in Cellular Neuroscience
Bmal1
circadian system
SCN
vGLUT
GLAST
VIP
title Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
title_full Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
title_fullStr Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
title_full_unstemmed Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
title_short Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
title_sort loss of bmal1 impairs the glutamatergic light input to the scn in mice
topic Bmal1
circadian system
SCN
vGLUT
GLAST
VIP
url https://www.frontiersin.org/articles/10.3389/fncel.2025.1538985/full
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