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Differences in glutamate uptake between cortical regions impact neuronal NMDA receptor activation

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Romanos Jennifer, Benke Dietmar, Saab Aiman, Zeilhofer Hanns Ulrich, Santello Mirko,
Project Cortical mechanisms controlling migraine pain
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Original article (peer-reviewed)

Journal Communications Biology
Page(s) 2
Title of proceedings Communications Biology

Open Access

Type of Open Access Publisher (Gold Open Access)


Rapid removal of synaptically-released glutamate from the extracellular space is necessary to spatially and temporally limit neuronal activation. In the adult mammalian CNS, glutamate uptake is performed primarily by astrocytes through high-affinity glutamate transporters. Recent evidence suggests that astrocytes may have specialized functions in specific circuits, but the extent and significance of such specialization are unclear. By performing direct patch-clamp recordings and two-photon glutamate imaging, we compared glutamate clearance in the frontal and somatosensory cortex and how this impacts neuronal function. We report that, in the somatosensory cortex, glutamate uptake by astrocytes is reduced during sustained synaptic stimulation, when compared to lower stimulation frequencies. Conversely, glutamate uptake capacity is increased in the frontal cortex during higher synaptic stimulation frequency, thereby limiting extracellular buildup of glutamate. This efficient glutamate clearance heavily relies on Na+/K+-ATPase function and is achieved by the simultaneous activation of GLT-1 and non-GLT-1 transporters, which reduce neuronal excitation by limiting NMDA receptor activation in layer 5 pyramidal neurons. Thus, increased glutamate uptake capacity in the frontal cortex, may prevent excessive neuronal excitation during intense synaptic activity. These results may explain why diseases associated with network hyperexcitability differentially affect individual brain areas.