ORCID: https://orcid.org/0000-0002-6336-566X; Negrean, Adrian ORCID: https://orcid.org/0000-0002-9256-7412; Chen, Yang ORCID: https://orcid.org/0000-0002-6774-3007; Iyer, Rishyashring ORCID: https://orcid.org/0000-0001-9126-9491; Reep, Daniel ORCID: https://orcid.org/0009-0009-7638-9538; Liu, Anyi; Palutla, Anirudh ORCID: https://orcid.org/0009-0000-3997-4943; Xie, Michael E. ORCID: https://orcid.org/0000-0002-4026-9181; MacLennan, Bryan J.; Hagihara, Kenta M.; Kinsey, Lucas W.; Sun, Julianna L.; Yao, Pantong; Zheng, Jihong ORCID: https://orcid.org/0000-0002-1247-6087; Tsang, Arthur; Tsegaye, Getahun; Zhang, Yonghai ORCID: https://orcid.org/0009-0004-6121-427X; Patel, Ronak H.; Arthur, Benjamin J. ORCID: https://orcid.org/0000-0003-3545-8807; Hiblot, Julien ORCID: https://orcid.org/0000-0002-7883-8079; Leippe, Philipp; Tarnawski, Miroslaw ORCID: https://orcid.org/0000-0001-5297-5668; Marvin, Jonathan S. ORCID: https://orcid.org/0000-0003-2294-4515; Vevea, Jason D.; Turaga, Srinivas C. ORCID: https://orcid.org/0000-0003-3247-6487; Tebo, Alison G. ORCID: https://orcid.org/0000-0003-0788-5617; Carandini, Matteo ORCID: https://orcid.org/0000-0003-4880-7682; Rossi, L. Federico ORCID: https://orcid.org/0000-0001-5831-4860; Kleinfeld, David ORCID: https://orcid.org/0000-0001-9797-4722; Konnerth, Arthur ORCID: https://orcid.org/0000-0002-9548-2676; Svoboda, Karel ORCID: https://orcid.org/0000-0002-6670-7362; Turner, Glenn C. ORCID: https://orcid.org/0000-0002-5341-2784; Hasseman, Jeremy P. ORCID: https://orcid.org/0000-0002-0096-7321 und Podgorski, Kaspar ORCID: https://orcid.org/0000-0002-0374-2005
(2026):
Glutamate indicators with increased sensitivity and tailored deactivation rates.
In: Nature Methods, Vol. 23: pp. 417-425
[PDF, 29MB]
Abstract
Understanding how neurons integrate signals from thousands of input synapses requires methods to monitor neurotransmission across many sites simultaneously. The fluorescent protein glutamate indicator iGluSnFR enables visualization of synaptic signaling, but the sensitivity, scale and speed of such measurements are limited by existing variants. Here we developed two highly sensitive fourth-generation iGluSnFR variants with fast activation and tailored deactivation rates: iGluSnFR4f for tracking rapid dynamics, and iGluSnFR4s for recording from large populations of synapses. These indicators detect glutamate with high spatial specificity and single-vesicle sensitivity in vivo. We used them to record natural patterns of synaptic transmission across multiple experimental contexts in mice, including two-photon imaging in cortical layers 1–4 and hippocampal CA1, and photometry in the midbrain. The iGluSnFR4 variants extend the speed, sensitivity and scalability of glutamate imaging, enabling direct observation of information flow through neural networks in the intact brain.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine > Munich Cluster for Systems Neurology (SyNergy) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-131244-8 |
| ISSN: | 1548-7091 |
| Annotation: | Published online December 23, 2025 |
| Language: | English |
| Item ID: | 131244 |
| Date Deposited: | 20. Jan 2026 13:26 |
| Last Modified: | 02. Jun 2026 12:36 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
Actions (login required)
- View Item
