BACKGROUND
Excitatory synaptic transmission in the nucleus accumbens (NAc) is a key biological substrate underlying behavioral responses to psychostimulants and susceptibility to relapse. Recent 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 (EPSCs) following viral-mediated expression of channelrhodopsin-2 in the mThal, prefrontal cortex (PFC), or basolateral amygdala (BLA) from acute brain slices. To identify NAc medium spiny neuron (MSN) subtypes we utilized mice expressing tdTomato driven by the promoter for the dopamine receptor subtype 1 (D1). We recorded N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) properties to evaluate synaptic adaptations induced by cocaine experience, a 5-day cocaine exposure followed by 2-weeks of abstinence.
RESULTS
We determine that excitatory inputs to the NAc core display differential NMDAR properties and cocaine experience uniquely alters AMPAR and NMDAR properties at mThal-D1(+), mThal-D1(−), and PFC-D1(+) synapses, but not PFC-D1(−) synapses. Finally, at mThal-D1(+) synapses, we demonstrate that cocaine enhances GluN2C/D function and NMDAR-dependent synaptic plasticity.
CONCLUSIONS
Our results identify contrasting cocaine-induced AMPAR and NMDAR modifications at mThal- and PFC-NAc core synapses. These changes include an enhancement of NMDAR function and plasticity at mThal-D1(+) synapses. Incorporation of GluN2C/D-containing NMDARs most likely underlies these phenomena and represents a potential therapeutic target for psychostimulant use disorders.