The Effect Of The Interaction Between Nucleus Accumbens DA Receptor And NMDA Receptor Subtypes On The Discharge Characteristics Of MSN

Mesocorticolimbic dopamine syetem(MLDS),is the basic circuit of drug addiction,whereas the nucleus accumbens(NAc)is the core of this loop.NAc receives glutamatergic afferents from prefrontal cortex(PFC),hippocampus,and amygdala,and dopaminergic afferents from ventral tegmental area(VTA).These projections converged on a single NAc medium spiny neuron(MSN).NAc accepts the effects of the dopamine(DA)system and the glutamate system simultaneously that the two systems are closely linked and have direct structural and functional connections.The interaction between the dopamine system and the glutamate system has been reported.For example,DA can regulate the loading of NMDA receptor(NMDAR)and AMPA receptor(AMPAR)in striatum.The D1R/NR1 complex regulates D1R-dependent NMDAR current enhancement and D1-MSN LTP formation.Direct action of D2R-NR2B is associated with enhanced cocaine-induced postsynaptic DA input in the striatum.All these evidences suggest that the interaction between the two systems affects the regulation of receptor function,synaptic conduction,and neural plasticity.However,it still unknown whether the interaction affects the excitability of neurons.In this study,by using whole-cell patch clamp electrophysiology with isolated brain slices,we observed the changes of the intrinsic excitability and spike adaptation of MSNs in NAc Shell area(NAcShell)induced by activation of NMDAR or DAR.Particularly,the effects of the interactions between DAR and NMDAR subtypes,D2R-NR2B and D1-NR2A,on firing properties of NAcShell MSNs were examinated.The main results are as following:1.NMDAR activation increased the intrinsic excitability and the spike adaptation of NAcShell MSNsNon-selective NMDAR activation significantly increased the intrinsic exicitability which is characterized by the dcreased rheobase and increased spike numbers at lower injected depolarizing current(100?250 pA).In contrast,NMDAR activation significantly decreased the spike train duration at higher injected depolarizing current(250?400 pA).Selective activation of NR2A-containing NMDAR significantly decreased the spike train duration but had no effects on the rheobase and the spike number,whereas selective activation of NR2B-containing NMDAR significantly increased the spike number but had no influence on the reobase.The results showed that NMDAR activation increased the intrinsic excitability and the spike adaptation of MSNs.Furthermore,NR2A-containing NMDAR activation enhanced the spike adaptation and NR2B-containing NMDAR activation increased the intrinsic excitability of MSNs.2.Application of Dopamine inhibited the enhancement of intrinsic excitablity of MSNs by NMDAR activationCompared with initial status,continuously activation of NMDAR after application of dopmine still decreased the spike train duration of MSN at higher injected depolarizing current but had no effect on the rheobase and the spike number at the lower injected depolarizing current of MSNs.The results showed that the activation of both D1R and D2R inhibited the increasement of intrinsic excitability induced by NMDAR.3.Effects of the interaction between DAR and NMDAR on the excitability of NAcShell MSNsCompared with the initial status,activation of NR2B-containing NMDAR after D2R activation significantly decreased the spike train duration at higher injected depolarizing current,but had no influence on the rheobase and spike numger at lower injected depolarizing current of MSNs.Compared with the initial status,activation of NR2A-containing NMDAR after D1R activation significantly decreased the spike train duration at higher injected depolarizing current,but had no effects on the rheobase and the spike number of MSNs at lower injected depolarizing current.The results showed that D2R activation inhibited the increasement of intrinsic excitability induced by NR2B-containing NMDAR activation.Moreover,DIR activation had no effect on the decrease of spike train duration induced by NR2A-containing NMDAR activation.In summary,the following conclusions can be drawn:NMDAR activation increased the intrinsic excitability and the spike adaptation of NAcShell MSNs.The enhancement of the spike adaptation was induced by NR2A-containing NMDAR activation and the increasement of the intrinsic excitability was induced by NR2B-containing NMDAR activation.DAR activation inhibited the enhancement of intrinsic excitability induced by NMDAR activation through the interaction between D2R and NR2B-containing NMDAR.