An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure.
Cristina Martín-Monteagudo, Javier Sánchez Romero, Julia Adams, Nagore Puente, Pedro Grandes, Giovanni Marsicano, Ana Covelo, Baljit S Khakh, Marta Navarrete
Nature Communications December 9, 2025 DOI: 10.1038/s41467-025-67166-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Cannabis |
| Key findings | THC-induced cognitive deficits require astrocytic glutamate release within a specific ventral hippocampus-NAc ensemble, and attenuating calcium activity in these astrocytes prevents spatial learning and synaptic plasticity impairments. |
Abstract
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.
Comparable studies
Other experimental studies on cannabis, most cited first.
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|---|---|---|---|
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| Which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like effects? Young cannabis users | 2018 | Observational study (naturalistic, within-subject counterbalanced design) | n = 410 |
| Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain Effects Healthy volunteers | 2018 | Experimental study | n = 5 |
| Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis Patients with multiple sclerosis who began using cannabis after disease onset, used it... | 2019 | Quasi-experimental study with odd-even allocation | n = 40 |