Exploring the Role of Astroglial Glutamate Release and Association With Synapses in Neuronal Function and Behavior

Biol Psychiatry. 2018 Dec 1;84(11):778-786. doi: 10.1016/j.biopsych.2017.10.029. Epub 2017 Nov 11.


Astrocytes are stellate cells whose appearance can resemble a pointed star, especially when visualizing glial fibrillary acidic protein, a canonical marker for astrocytes. Accordingly, there is a commonly made connection between the points of light that shine in the night sky and the diffuse and abundant cells that buffer ions and provide support for neurons. An exceptional amount of function has been attributed to, negated for, and potentially reaffirmed for these cells, especially regarding their ability to release neuroactive molecules and influence synaptic plasticity. This makes the precise role of astrocytes in tuning neural communication seem difficult to grasp. However, data from animal models of addiction demonstrate that a variety of drug-induced molecular adaptations responsible for relapse vulnerability take place in astrocyte systems that regulate glutamate uptake and release. These findings highlight astrocytes as a critical component of the neural systems responsible for addiction, serving as a key component of the plasticity responsible for relapse and drug seeking. Here I assemble recent findings that utilize genetic tools to selectively manipulate or measure flux of internal calcium in astrocytes, focusing on G protein-coupled receptor-mediated mobilization of calcium and the induction of glutamate release. Further, I compile evidence regarding astrocyte glutamate release as well as astrocyte association with synapses with respect to the impact of these cellular phenomena in shaping synaptic transmission. I also place these findings in the context of the previous studies of Scofield et al., who explored the role of astrocytes in the nucleus accumbens in the neural mechanisms underlying cocaine seeking.

Keywords: Astrocyte; Calcium; Cocaine; GPCR; Gliotransmission; Glutamate.

Publication types

  • Research Support, N.I.H., Extramural
  • Review
  • Video-Audio Media

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Calcium Channels, N-Type / metabolism
  • Cocaine / administration & dosage
  • Dopamine Uptake Inhibitors / administration & dosage
  • Drug-Seeking Behavior
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / metabolism*
  • Humans
  • Neuronal Plasticity
  • Neurons / physiology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Synapses / physiology*
  • Synaptic Transmission / physiology


  • Calcium Channels, N-Type
  • Dopamine Uptake Inhibitors
  • Glial Fibrillary Acidic Protein
  • Glutamic Acid
  • Cocaine