Abstract

Background Excitatory synaptic transmission in the nucleus accumbens (NAc) is a key biological substrate underlying behavioral responses to psychostimulants and susceptibility to relapse. Studies have demonstrated that cocaine induces changes in glutamatergic signaling at distinct inputs to the NAc. However, consequences of cocaine experience on synaptic transmission from the midline nuclei of the thalamus (mThal) to the NAc have yet to be reported.

Methods To examine synapses from specific NAc core inputs, we recorded light-evoked excitatory postsynaptic currents following viral-mediated expression of channelrhodopsin-2 in the mThal, prefrontal cortex (PFC), or basolateral amygdala from acute brain slices. To identify NAc medium spiny neuron subtypes, we used mice expressing tdTomato driven by the promoter for dopamine receptor subtype 1 (D 1 ). We recorded N-methyl-D-aspartate receptor (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) properties to evaluate synaptic adaptations induced by cocaine experience, a 5-day cocaine exposure followed by 2 weeks of abstinence.

Results Excitatory inputs to the NAc core displayed differential NMDAR properties, and cocaine experience uniquely altered AMPAR and NMDAR properties at mThal-D1(+), mThal-D1(−), and PFC-D1(+) synapses, but not at PFC-D1(−) synapses. Finally, at mThal-D1(+) synapses, cocaine enhanced GluN2C/D function and NMDAR-dependent synaptic plasticity.