Fear Erasure Facilitated by Immature Inhibitory Neuron Transplantation

Abstract

Transplantation of embryonic γ-aminobutyric acid (GABA)ergic neurons has been shown to modify disease phenotypes in rodent models of neurologic and psychiatric disorders. However, whether transplanted interneurons modulate fear memory remains largely unclear. Here, we report that transplantation of embryonic interneurons into the amygdala does not alter host fear memory formation. Yet approximately 2 weeks after transplantation, but not earlier or later, extinction training produces a marked reduction in spontaneous recovery and renewal of fear response. Further analyses reveal that transplanted interneurons robustly form functional synapses with neurons of the host amygdala and exhibit similar developmental maturation in electrophysiological properties as native amygdala interneurons. Importantly, transplanted immature interneurons reduce the expression of perineuronal nets, promote long-term synaptic plasticity, and modulate both excitatory and inhibitory synaptic transmissions of the host circuits. Our findings demonstrate that transplanted immature interneurons modify amygdala circuitry and suggest a previously unknown strategy for the prevention of extinction-resistant pathological fear.

Keywords: amygdala; embryonic interneuron; fear extinction; fear recovery; immature neuron; synaptic plasticity; transplantation.