Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition

Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons. This form of plasticity is expressed postsynaptically and requires both CaMKIIα and the β2 subunit of the GABA-A receptor. Importantly, this process may function to preserve dendritic inhibition, as genetic deletion of NMDAR signaling results in a selective weakening of dendritic inhibition. Overall, our results reveal a new mechanism for linking excitatory and inhibitory input in neuronal dendrites and provide novel insight into the homeostatic regulation of synaptic transmission in cortical circuits. •Activation of NMDARs potentiates GABAergic inhibition from SOM-INs•Dendritic, but not perisomatic, GABAergic synapses are sensitive to CaMKIIα activity•GABAergic potentiation requires expression of the GABAAR β2 subunit•Loss of NMDARs alters the balance of inhibition along the somatodendritic axis Using electrophysiology and optogenetics, Chiu et al. show that activation of NMDA-type glutamate receptors selectively potentiates inhibition from somatostatin-expressing interneurons onto cortical pyramidal cells. This work suggests a mechanism for regulating the balance of excitation and inhibition in neuronal dendrites.