Auditory associative learning drives synaptic responses in tail of the striatum spiny projection neurons

The association of cues with the absence or presence of danger is crucial to survival. The synaptic changes that enable association with the absence of danger are unknown, but a role for the tail of the striatum (TS) has been implicated. To investigate this, we conditioned mice to associate a contextual environment with the threat of foot-shock, which led to freezing, and a sound cue (CS) with the absence of shock, which suppressed contextual freezing. After learning, the CS strongly activated SPNs relative to controls, including a large direct pathway (dSPN) calcium response to sound onset that persisted during anesthesia. In the brain slices of conditioned mice, dSPNs exhibited enhanced synaptic responses to auditory thalamic inputs, with higher NMDA and AMPA receptor-mediated responses, decreased GABAergic inputs, and increased density of dendritic spines. Thus, auditory association with the absence of danger involves enhancement of TS synaptic responses to the associated sound.