Astrocytes gate Hebbian synaptic plasticity in the striatum

• Published in: Nature communications Vol. 7; no. 1; p. 13845
• Main Authors: Valtcheva, Silvana, Venance, Laurent
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.12.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1595/2167; 631/378/2591/2595; 631/378/2596/1308; 631/378/87; 9/74; Action Potentials; Amino acids; Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - physiology; Ceftriaxone - pharmacology; Contingency; Corpus Striatum - cytology; Corpus Striatum - drug effects; Corpus Striatum - physiology; Emergence; Excitatory Amino Acid Transporter 2 - agonists; Excitatory Amino Acid Transporter 2 - antagonists & inhibitors; Excitatory Amino Acid Transporter 2 - physiology; gamma-Aminobutyric Acid - physiology; Hebbian plasticity; Humanities and Social Sciences; In Vitro Techniques; Investigations; Life Sciences; Long-Term Potentiation; Long-Term Synaptic Depression; Male; Models, Neurological; multidisciplinary; Neostriatum; Neural plasticity; Neuronal Plasticity - physiology; Physiology; Plasticity; Rats; Receptors, N-Methyl-D-Aspartate - physiology; Science; Science (multidisciplinary); Sensory Gating; Synaptic plasticity; Variance analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13845

Astrocytes, via excitatory amino-acid transporter type-2 (EAAT2), are the major sink for released glutamate and contribute to set the strength and timing of synaptic inputs. The conditions required for the emergence of Hebbian plasticity from distributed neural activity remain elusive. Here, we investigate the role of EAAT2 in the expression of a major physiologically relevant form of Hebbian learning, spike timing-dependent plasticity (STDP). We find that a transient blockade of EAAT2 disrupts the temporal contingency required for Hebbian synaptic plasticity. Indeed, STDP is replaced by aberrant non-timing-dependent plasticity occurring for uncorrelated events. Conversely, EAAT2 overexpression impairs the detection of correlated activity and precludes STDP expression. Our findings demonstrate that EAAT2 sets the appropriate glutamate dynamics for the optimal temporal contingency between pre- and postsynaptic activity required for STDP emergence, and highlight the role of astrocytes as gatekeepers for Hebbian synaptic plasticity. Astrocytes regulate synaptic signalling via EAAT glutamate uptake, though whether they play a role in Hebbian plasticity is unknown. Here, the authors find targeting EAAT2 disrupts the emergence of spike timing-dependent plasticity, which highlights the role of astrocytes as gatekeepers for Hebbian plasticity.