Abstract
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.
Highlights
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
Baseline excitatory postsynaptic currents (EPSCs) were recorded for 10 min in voltage–clamp mode and recordings were switched to current–clamp mode to pair a single excitatory postsynaptic potential (EPSP) induced by presynaptic stimulation with a single postsynaptic spike induced by a brief depolarization of the medium-sized spiny neurons (MSNs) (Fig. 1b)
Our findings demonstrate that astrocytes play a key role in the establishment of spike timing-dependent plasticity (STDP), through EAAT2-mediated glutamate uptake
Summary
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. We investigate the role of EAAT2 in the expression of a major physiologically relevant form of Hebbian learning, spike timing-dependent plasticity (STDP). 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. Fast removal of glutamate by astrocytes contributes to set the strength and timing of synaptic inputs by controlling periand extrasynaptic receptor activation during neuronal activity[18]. We demonstrate here that astrocytes, via EAAT2, set the appropriate glutamate dynamics for the emergence and the establishment of synaptic Hebbian learning rule, such as STDP
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
