Neuron
Volume 108, Issue 5, 9 December 2020, Pages 919-936.e11
Journal home page for Neuron

Article
LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia

https://doi.org/10.1016/j.neuron.2020.08.030Get rights and content
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Highlights

  • Induction of synaptic LTP prompts withdrawal of perisynaptic astroglia

  • The underlying mechanisms involve NKCC1 transporter and cofilin

  • Reduced synaptic astroglial coverage boosts extrasynaptic glutamate escape

  • LTP induction thus enhances NMDAR-dependent inter-synaptic cross-talk

Summary

Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localization reveal that LTP induction thus prompts spatial retreat of astroglial glutamate transporters, boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which a memory trace at one synapse could alter signal handling by multiple neighboring connections.

Keywords

Excitatory synapse
long-term potentiation
glutamate spillover
perisynaptic astroglial processes
astrocyte plasticity
glutamate sensor imaging
super-resolution microscopy
hippocampus
whisker stimulation
barrel cortex

Cited by (0)

13

These authors contributed equally

14

Lead Contact

15

Dr Nagelhus sadly passed away on 10 January 2020