Author
Listed:
- Roberta de Ceglia
(University of Lausanne)
- Ada Ledonne
(University of Lausanne
IRCCS Santa Lucia Foundation)
- David Gregory Litvin
(University of Lausanne
Wyss Center for Bio and Neuro Engineering, Campus Biotech)
- Barbara Lykke Lind
(University of Lausanne
University of Copenhagen)
- Giovanni Carriero
(University of Lausanne)
- Emanuele Claudio Latagliata
(IRCCS Santa Lucia Foundation)
- Erika Bindocci
(University of Lausanne)
- Maria Amalia Di Castro
(Sapienza University)
- Iaroslav Savtchouk
(University of Lausanne
Marquette University)
- Ilaria Vitali
(University of Lausanne)
- Anurag Ranjak
(University of Lausanne)
- Mauro Congiu
(University of Lausanne)
- Tara Canonica
(University of Lausanne)
- William Wisden
(Imperial College London)
- Kenneth Harris
(University College London)
- Manuel Mameli
(University of Lausanne)
- Nicola Mercuri
(IRCCS Santa Lucia Foundation
University of Rome “Tor Vergata”)
- Ludovic Telley
(University of Lausanne)
- Andrea Volterra
(University of Lausanne
Wyss Center for Bio and Neuro Engineering, Campus Biotech)
Abstract
Multimodal astrocyte–neuron communications govern brain circuitry assembly and function1. For example, through rapid glutamate release, astrocytes can control excitability, plasticity and synchronous activity2,3 of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions4–7. For astrocytes to communicate through fast focal glutamate release, they should possess an apparatus for Ca2+-dependent exocytosis similar to neurons8–10. However, the existence of this mechanism has been questioned11–13 owing to inconsistent data14–17 and a lack of direct supporting evidence. Here we revisited the astrocyte glutamate exocytosis hypothesis by considering the emerging molecular heterogeneity of astrocytes18–21 and using molecular, bioinformatic and imaging approaches, together with cell-specific genetic tools that interfere with glutamate exocytosis in vivo. By analysing existing single-cell RNA-sequencing databases and our patch-seq data, we identified nine molecularly distinct clusters of hippocampal astrocytes, among which we found a notable subpopulation that selectively expressed synaptic-like glutamate-release machinery and localized to discrete hippocampal sites. Using GluSnFR-based glutamate imaging22 in situ and in vivo, we identified a corresponding astrocyte subgroup that responds reliably to astrocyte-selective stimulations with subsecond glutamate release events at spatially precise hotspots, which were suppressed by astrocyte-targeted deletion of vesicular glutamate transporter 1 (VGLUT1). Furthermore, deletion of this transporter or its isoform VGLUT2 revealed specific contributions of glutamatergic astrocytes in cortico-hippocampal and nigrostriatal circuits during normal behaviour and pathological processes. By uncovering this atypical subpopulation of specialized astrocytes in the adult brain, we provide insights into the complex roles of astrocytes in central nervous system (CNS) physiology and diseases, and identify a potential therapeutic target.
Suggested Citation
Roberta de Ceglia & Ada Ledonne & David Gregory Litvin & Barbara Lykke Lind & Giovanni Carriero & Emanuele Claudio Latagliata & Erika Bindocci & Maria Amalia Di Castro & Iaroslav Savtchouk & Ilaria Vi, 2023.
"Specialized astrocytes mediate glutamatergic gliotransmission in the CNS,"
Nature, Nature, vol. 622(7981), pages 120-129, October.
Handle:
RePEc:nat:nature:v:622:y:2023:i:7981:d:10.1038_s41586-023-06502-w
DOI: 10.1038/s41586-023-06502-w
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Cited by:
- Péter Berki & Csaba Cserép & Zsuzsanna Környei & Balázs Pósfai & Eszter Szabadits & Andor Domonkos & Anna Kellermayer & Miklós Nyerges & Xiaofei Wei & Istvan Mody & Araki Kunihiko & Heinz Beck & He Ka, 2024.
"Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices,"
Nature Communications, Nature, vol. 15(1), pages 1-24, December.
- Eiji Shigetomi & Hideaki Suzuki & Yukiho J. Hirayama & Fumikazu Sano & Yuki Nagai & Kohei Yoshihara & Keisuke Koga & Toru Tateoka & Hideyuki Yoshioka & Youichi Shinozaki & Hiroyuki Kinouchi & Kenji F., 2024.
"Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2,"
Nature Communications, Nature, vol. 15(1), pages 1-18, December.
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