Spatial organization of neuron–astrocyte interactions in the somatosensory cortex

Andrés M. Baraibar, Lindsey Belisle, Giovanni Marsicano, Carlos Matute, Susana Mato, Alfonso Araque, Paulo Kofuji

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Microcircuits in the neocortex are functionally organized along layers and columns, which are the fundamental modules of cortical information processing. While the function of cortical microcircuits has focused on neuronal elements, much less is known about the functional organization of astrocytes and their bidirectional interaction with neurons. Here, we show that Cannabinoid type 1 receptor (CB1R)-mediated astrocyte activation by neuron-released endocannabinoids elevate astrocyte Ca2+ levels, stimulate ATP/adenosine release as gliotransmitters, and transiently depress synaptic transmission in layer 5 pyramidal neurons at relatively distant synapses (>20 μm) from the stimulated neuron. This astrocyte-mediated heteroneuronal synaptic depression occurred between pyramidal neurons within a cortical column and was absent in neurons belonging to adjacent cortical columns. Moreover, this form of heteroneuronal synaptic depression occurs between neurons located in particular layers, following a specific connectivity pattern that depends on a layer-specific neuron-to-astrocyte signaling. These results unravel the existence of astrocyte-mediated nonsynaptic communication between cortical neurons and that this communication is column- and layer-specific, which adds further complexity to the intercellular signaling processes in the neocortex.

Original languageEnglish (US)
Pages (from-to)4498-4511
Number of pages14
JournalCerebral Cortex
Issue number8
StatePublished - Apr 15 2023

Bibliographical note

Funding Information:
Postdoctoral fellowship from Basque Government, Spain, to AMB; National Institutes of Health (NIH-MH R01MH119355 to AA and PK; NIH-NINDS R01NS097312-to AA; and NIH-NIDA R01DA048822 to AA); Department of Defense (W911NF2110328) to AA; FEDER and ISCIII (AES2018-PI18/00513); Basque Government (PIBA19-0059 to SM); ARSEP Foundation to SM and GM.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press. All rights reserved.


  • astrocyte
  • calcium imaging
  • cortex
  • neuron-astrocyte communication
  • synaptic transmission

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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