Glutamatergic transmission in the nucleus accumbens shell (NAcSh) is a substrate for reward learning and motivation. Metabotropic glutamate (mGlu) receptors regulate NAcSh synaptic strength by inducing long-term depression (LTD). Inputs from prefrontal cortex (PFC) and medio-dorsal thalamus (MDT) drive opposing motivated behaviors yet mGlu receptor regulation of these synapses is unexplored. We examined Group I mGlu receptor regulation of PFC and MDT glutamatergic synapses onto specific populations of NAc medium spiny neurons (MSNs) using D1tdTom BAC transgenic mice and optogenetics. Synaptically evoked long-term depression (LTD) at MDT-NAcSh synapses required mGlu₅ but not mGlu₁ and was specific for D1(+) MSNs, whereas PFC LTD was expressed at both D1(+) and D1(-) MSNs and required mGlu₁ but not mGlu₅. Two weeks after five daily non-contingent cocaine exposures (15 mg/kg), LTD was attenuated at MDT-D1(+) synapses but was rescued by the mGlu5-positive allosteric modulator (PAM) VU0409551. These results highlight unique plasticity mechanisms regulating specific NAcSh synapses.

中文翻译：

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mGlu1和mGlu5调节伏隔核壳的不同兴奋性输入。

伏伏核壳（NAcSh）中的谷氨酸能传递是奖励学习和动机的基础。代谢型谷氨酸（mGlu）受体通过诱导长期抑郁（LTD）来调节NAcSh突触强度。前额叶皮层（PFC）和中背丘脑（MDT）的输入驱动相反的动机行为，但尚未探索这些突触的mGlu受体调节。我们使用D1tdTom BAC转基因小鼠和光遗传学方法研究了I类mGlu受体对PFC和MDT谷氨酸能突触对NAc中等多刺神经元（MSNs）特定种群的调节。MDT-NAcSh突触的突触诱发的长期抑郁症（LTD）需要mGlu _5，但不需要mGlu ₁并且是D1（+）MSN特有的，而PFC LTD在D1（+）和D1（-）MSN上均表达，并且需要mGlu ₁而不是mGlu ₅。每天五次非临时性可卡因暴露（15 mg / kg）两周后，LTD在MDT-D1（+）突触处减弱，但被mGlu5阳性变构调节剂（PAM）VU0409551拯救。这些结果突出了调节特定NAcSh突触的独特可塑性机制。