An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure
Nat Commun. 2025-12-09; :
DOI: 10.1038/s41467-025-67166-w
Lire sur PubMed
https://www.bordeaux-neurocampus.fr/12351
Martín-Monteagudo C(1), Sánchez Romero J(1), Adams JM(2), Puente N(3)(4),
Grandes P(3)(4), Marsicano G(5), Covelo A(5)(6)(7), Khakh BS(2), Navarrete
M(8)(9).
Author information:
(1)Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid,
Spain.
(2)Department of Physiology, University of California Los Angeles, Los Angeles,
CA, USA.
(3)Department of Neurosciences, Faculty of Medicine and Nursing, University of
the Basque Country UPV/EHU, Leioa, Spain.
(4)Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Leioa,
Spain.
(5)Université de Bordeaux, INSERM, Neurocentre Magendie, Bordeaux, France.
(6)CINBIO, University of Vigo, Vigo, Spain.
(7)Galicia Sur Health Research Institute (IISGS), Laboratory of Neuroscience,
Vigo, Spain.
(8)Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid,
Spain. .
(9)Centro de Neurociencias Cajal, Consejo Superior de Investigaciones
Científicas, Alcalá de Henares, Spain. .
Cannabis is the most widely used illicit drug, particularly during adolescence.
Its consumption disrupts glutamate homeostasis and synaptic plasticity in the
nucleus accumbens (NAc). Here, we identify a functionally distinct accumbal
astrocytic ensemble, associated with the ventral hippocampus-NAc (vHip→NAc)
circuit, that is critical for tetrahydrocannabinol (THC)-induced synaptic and
behavioral impairments. We employed the AstroLight tool to selectively
manipulate this astrocytic ensemble. Our findings reveal that THC increases
astrocytic calcium activity and glutamatergic tone within the NAc. These
glutamatergic alterations are absent in astrocyte-specific p38α knockout mice,
implicating p38α signaling in astrocyte-mediated plasticity. Astrocytic
glutamate release within the vHip→NAc ensemble is required for THC-induced
cognitive deficits, and targeted attenuation of THC-induced calcium activity in
this ensemble prevents spatial learning and synaptic plasticity impairments.
These results highlight a critical role for astrocytic ensembles in shaping
behavior and emphasize their potential as therapeutic targets for mitigating the
cognitive consequences of THC exposure.
© 2025. The Author(s).
DOI: 10.1038/s41467-025-67166-w
PMID: 41360811
Conflict of interest statement: Competing interests: The authors declare no
competing interests.