Astrocytes gate Hebbian synaptic plasticity in the striatum

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.

Unravelling and Exploiting Astrocyte Dysfunction in Huntington’s Disease

“…In Q175 mice, EPSC decay was slowed [93], notably when the EPSC included NMDAR-mediated currents at membrane potentials of +50 mV and higher. This observation is in line with the results from normal mice and rats where pharmacological block of GLT1 with TBOA induced EPSC prolongation [94] and changes in the preferentially expressed type of plasticity [82]. It was suggested that GLT1 blockade results in the recruitment of a critical number of perisynaptic NMDA receptors to elicit non-Hebbian forms of plasticity at the expense of spike-time dependent plasticity (STDP).…”

“…Some of the iGluSnFR and Ca 2+ signal alterations observed in R6/2 mice could be rescued by astrocyte delivery of Kir4.1 [81]. Thus, it appears that Kir4.1 can set into effect a sequence of events that results in restoration of normal astrocyte ion and membrane potential gradients, recovery of GLT1 function, reduced perisynaptic glutamate levels as well as altered synaptic transmission and plasticity [82] in HD model mice. However, there was no evidence for elevated astrocyte glutamate release, which had been suggested based on cell-culture work [83].…”

“…While in normal mice glutamate transport is hardly ever overwhelmed [91], slowed glutamate uptake and spillover to perisynaptic sites are now being considered in some mechanisms of synaptic plasticity [82] and in neurological conditions, including HD. Recent experiments with the fluorescent glutamate sensor iGluSnFR illuminate the reduced glutamate clearance capacity of striatal astrocytes in R6/2 mice [81].…”

Synaptic Barristor Based on Phase‐Engineered 2D Heterostructures

“…The neuromodulator such as an astrocyte was recently proposed to play a critical role in www.advmat.de www.advancedsciencenews.com cellular programing to achieve a high level of neural information processing. [45][46][47][48] As shown in Figure 4a, here, we define the gate, drain, and source terminals of the synaptic device as a neuromodulator, pre-and postneurons, respectively. [45][46][47][48] As shown in Figure 4a, here, we define the gate, drain, and source terminals of the synaptic device as a neuromodulator, pre-and postneurons, respectively.…”

“…[45] Importantly, in those synapses, synaptic transmission can be further activated by intimate association of pre-and postsynaptic membranes with the surrounding neuromodulator. [45][46][47][48] As shown in Figure 4a, here, we define the gate, drain, and source terminals of the synaptic device as a neuromodulator, pre-and postneurons, respectively. Unlike conventional twoneuronal-based synaptic devices, the synaptic weight in the synaptic barristor can be additionally controlled by modulating the V G independent of the input spikes from neurons, where the role of the gate terminal is analogous to that of a neuromodulator as the gatekeeper for synaptic plasticity.…”