Kasugai et al Neuron 2019 D-16-02077R1

Associative learning is thought to involve different forms of activity-dependent synaptic plasticity. While previous studies have mostly focused on learning-related changes occurring at excitatory glutamatergic synapses, we found that associative learning such as fear conditioning also entails long-lasting functional and structural plasticity of GABAergic synapses onto pyramidal neurons of the murine basal amygdala. Fear conditioning-mediated structural remodeling of GABAergic synapses was associated with a change in mIPSC kinetics and an increase in the fraction of synaptic benzodiazepine-sensitive (BZD) GABAA receptors containing the α2 subunit, without altering the intrasynaptic distribution and overall amount of BZD-GABAA receptors. These structural and functional synaptic changes were partly reversed by extinction training. These findings provide evidence that associative learning, such as Pavlovian fear conditioning and extinction, sculpts inhibitory synapses to regulate inhibition of active neuronal networks, a process which may tune amygdala circuit responses to threat.