# CRCNS US-German Research Proposal: Quantitative and Computational Dissection of Glutamatergic Crosstalk at Tripartite Synapses > **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2023 · $125,824 ## Abstract CRCNS US-German Research Proposal: Quantitative and computational dissection of glutamatergic crosstalk at tripartite synapses (1) Christine R Rose, Heinrich Heine University, Düsseldorf, Germany (2) Christian Henneberger, University of Bonn, Germany (3) Ghanim Ullah, University of South Florida, Tampa, FL, USA Project Description 1 Introduction and Background Transmission at chemical synapses is the central mechanism by which information is transferred between neurons. Synaptic connections such as glutamatergic excitatory synapses are often perceived and modeled as point-to-point connections. However, there is substantial evidence that crosstalk between various glutamatergic synapses can occur when the presynaptically released glutamate is sensed not only by its direct postsynaptic partner but also by nearby synapses of the same and other neurons [4]. Notably, this phenomenon termed “glutamate spillover” not only defines the input-specificity of a given synaptic connection and its crosstalk to neighboring synapses, but is also involved in and controlled by activity-dependent plasticity [1, 7, 8]. How easily glutamate escapes from its release site and how far it spreads into the tissue depends on the morphological and molecular properties of the extracellular space (ECS) as well as on the efficacy of glutamate clearance, which primarily depends on astrocytic uptake [11, 12]. We and others have shown that the efficacy of perisynaptic glutamate uptake by astrocytes displays a remarkable heterogeneity between brain regions and, importantly, can vary drastically from one synapse to the next within a brain region [3, 7, 8]. This is in part because the morphological coverage of synapses by perisynaptic astrocyte processes (PAPs) can differ strongly between individual synapses [14]. Moreover, the Henneberger lab has recently shown that higher synaptic coverage by PAPs correlates with a higher local efficacy of glutamate uptake [3]. We have also demonstrated that in addition to being heterogeneous, astrocytic glutamate uptake and PAPs morphology both are controlled by neuronal plasticity [1]. Moreover, glutamate uptake is governed by the transporters’ stoichiometry, importing one glutamate molecule into the astrocyte by using the energy gained from co-transporting three Na+ and one proton down the electrochemical gradients, whilst also exporting one K+ [12]. While the inwardly-directed Na+ gradient is the main driving force for glutamate uptake, recent work by Rose lab and others have shown that glutamatergic activity causes local or global Na+ transients in astrocytes ([Na+]A) [15]. In the mouse hippocampus, astrocytic Na+ signals in fact arise predominately due to the activity of glutamate transporters themselves, degrading the Na+ gradient and thereby transiently weakening uptake capacity in a negative feedback-loop [15-17]. In the neocortex, glutamatergic synaptic activity in addition results in prominent Na+ influx through NMDA receptors, boostin... ## Key facts - **NIH application ID:** 10612169 - **Project number:** 1R01NS130916-01 - **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA - **Principal Investigator:** Ghanim Ullah - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2023 - **Award amount:** $125,824 - **Award type:** 1 - **Project period:** 2023-02-15 → 2027-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10612169 ## Citation > US National Institutes of Health, RePORTER application 10612169, CRCNS US-German Research Proposal: Quantitative and Computational Dissection of Glutamatergic Crosstalk at Tripartite Synapses (1R01NS130916-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10612169. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*