Safety learning induces postsynaptic potentiation of direct pathway spiny projection neurons in the tail of the striatum

The association of a sensory cue with an outcome is a crucial step in learning to identify safe versus threatening situations. Here we assessed how learned sound-safety association alters neuronal activity in tail of the striatum (TS), where auditory cortical and thalamic inputs converge. Prior to training, foot shock elicited responses by TS direct and indirect pathway spiny projection neurons (SPNs), while sound tones produced no response. However, once the sound association was learned, sound tones strongly activated TS SPNs, even when the animal was under anesthesia. This conditioned auditory response occurred concurrently with alterations of direct pathway SPNs in the TS, including increased responses to cortical and auditory thalamic inputs, increased excitatory response with an enhanced ratio of NMDA to AMPA receptors, decreased responses to inhibitory input, and increased dendritic spines. This convergence of postsynaptic changes provides responses to relevant auditory cues during associative learning. TeaserSound-safety association enhances response to learned sound in striatal neurons via postsynaptic mechanisms