An astrocytic ensemble at vHip-NAc synapses modulates cognitive impairments induced by chronic tetrahydrocannabinol exposure.
Nature Communications December 9, 2025 Cristina Martín-Monteagudo, Javier Sánchez Romero, Julia Adams et al.
Cannabis, the most widely used illicit drug, is often consumed during adolescence. Its active component, THC, disrupts glutamate balance and synaptic plasticity in the nucleus accumbens (NAc). A specific group of astrocytes in the NAc, linked to the ventral hippocampus-NAc circuit, is critical for these effects. Using the AstroLight tool, researchers found that THC increases calcium activity and glutamate release in these astrocytes. This glutamate release depends on p38α signaling, as mice lacking astrocytic p38α showed no such changes. Blocking THC-induced calcium activity in this astrocyte ensemble prevented spatial learning and synaptic plasticity impairments, highlighting these astrocytes as potential therapeutic targets.