| Summary: | Summary: Dendritic inhibitory synapses are most efficient in modulating excitatory inputs localized on the same dendrite, but it is unknown whether their location is random or regulated. Here, we show that the formation of inhibitory synapses can be directed by excitatory synaptic activity on the same dendrite. We stimulated dendritic spines close to a GABAergic axon crossing by pairing two-photon glutamate uncaging with postsynaptic depolarization in CA1 pyramidal cells. We found that repeated spine stimulation promoted growth of a GABAergic bouton onto the same dendrite. The dendritic feedback signal required postsynaptic activation of DAGL, which produces the endocannabinoid 2-AG, and was mediated by CB1 receptors. We could also induce inhibitory bouton growth by local, brief applications of 2-AG. Our findings reveal a dendritic signaling mechanism to trigger growth of an inhibitory bouton at dendritic locations with strong excitatory synaptic activity, and this mechanism may serve to ensure inhibitory control over clustered excitatory inputs. : Inhibitory synapses control dendritic inputs with high spatial precision, but it is unclear how the location of new inhibitory synapses is determined. Hu et al. show that clustered excitatory activity can trigger endocannabinoid-mediated growth of an inhibitory bouton onto the same dendrite, suggesting activity-dependent coordination of excitatory and inhibitory synapses. Keywords: two-photon microscopy, two-photon glutamate uncaging, inhibitory synapses, presynaptic boutons, synapse formation, endocannabinoid signaling, E/I balance, dendritic computation, activity-dependent adaptation
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