Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs

Glutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-rel...

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Main Authors: Himawari Hirai, Kohtarou Konno, Miwako Yamasaki, Masahiko Watanabe, Takeshi Sakaba, Yuki Hashimotodani
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-12-01
Series:eLife
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Online Access:https://elifesciences.org/articles/99711
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author Himawari Hirai
Kohtarou Konno
Miwako Yamasaki
Masahiko Watanabe
Takeshi Sakaba
Yuki Hashimotodani
author_facet Himawari Hirai
Kohtarou Konno
Miwako Yamasaki
Masahiko Watanabe
Takeshi Sakaba
Yuki Hashimotodani
author_sort Himawari Hirai
collection DOAJ
description Glutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-release glutamate and GABA, exhibit differences between glutamate and GABA release properties in paired-pulse ratio, Ca2+-sensitivity, presynaptic receptor modulation, and Ca2+ channel-vesicle coupling configuration. Moreover, uniquantal synaptic responses show independent glutamatergic and GABAergic responses. Morphological analysis reveals that most SuM terminals form distinct glutamatergic and GABAergic synapses in proximity, each characterized by GluN1 and GABAAα1 labeling, respectively. Notably, glutamate/GABA co-transmission exhibits distinct short-term plasticities, with frequency-dependent depression of glutamate and frequency-independent stable depression of GABA. Our findings suggest that glutamate and GABA are co-released from different synaptic vesicles within the SuM terminals, and reveal that distinct transmission modes of glutamate/GABA co-release serve as frequency-dependent filters of SuM inputs.
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spelling doaj-art-306c9dfcae0447b4b2d05bd97bc795472024-12-16T15:46:41ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.99711Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputsHimawari Hirai0Kohtarou Konno1Miwako Yamasaki2https://orcid.org/0000-0003-4974-9349Masahiko Watanabe3https://orcid.org/0000-0001-5037-7138Takeshi Sakaba4https://orcid.org/0000-0003-0688-7717Yuki Hashimotodani5https://orcid.org/0000-0001-6723-2736Graduate School of Brain Science, Doshisha University, Kyoto, JapanDepartment of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, JapanDepartment of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, JapanDepartment of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, JapanGraduate School of Brain Science, Doshisha University, Kyoto, JapanGraduate School of Brain Science, Doshisha University, Kyoto, JapanGlutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-release glutamate and GABA, exhibit differences between glutamate and GABA release properties in paired-pulse ratio, Ca2+-sensitivity, presynaptic receptor modulation, and Ca2+ channel-vesicle coupling configuration. Moreover, uniquantal synaptic responses show independent glutamatergic and GABAergic responses. Morphological analysis reveals that most SuM terminals form distinct glutamatergic and GABAergic synapses in proximity, each characterized by GluN1 and GABAAα1 labeling, respectively. Notably, glutamate/GABA co-transmission exhibits distinct short-term plasticities, with frequency-dependent depression of glutamate and frequency-independent stable depression of GABA. Our findings suggest that glutamate and GABA are co-released from different synaptic vesicles within the SuM terminals, and reveal that distinct transmission modes of glutamate/GABA co-release serve as frequency-dependent filters of SuM inputs.https://elifesciences.org/articles/99711co-releasesupramammillary nucleushippocampusshort-term plasticitydentate gyrussynaptic transmission
spellingShingle Himawari Hirai
Kohtarou Konno
Miwako Yamasaki
Masahiko Watanabe
Takeshi Sakaba
Yuki Hashimotodani
Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs
eLife
co-release
supramammillary nucleus
hippocampus
short-term plasticity
dentate gyrus
synaptic transmission
title Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs
title_full Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs
title_fullStr Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs
title_full_unstemmed Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs
title_short Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs
title_sort distinct release properties of glutamate gaba co transmission serve as a frequency dependent filtering of supramammillary inputs
topic co-release
supramammillary nucleus
hippocampus
short-term plasticity
dentate gyrus
synaptic transmission
url https://elifesciences.org/articles/99711
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