Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
J Neurosci. 2022 Aug 24;42(34):6581-6592. doi: 10.1523/JNEUROSCI.0838-22.2022. Epub 2022 Jul 15.
The nucleus accumbens shell (NAcSh) is a key brain region where environmental cues acquire incentive salience to reinforce motivated behaviors. Principal medium spiny neurons (MSNs) in the NAcSh receive extensive glutamatergic projections from limbic regions, among which, the ventral hippocampus (vH) transmits information enriched in contextual cues, and the basolateral amygdala (BLA) encodes real-time arousing states. The vH and BLA project convergently to NAcSh MSNs, both activated in a time-locked manner on a cue-conditioned motivational action. In brain slices prepared from male and female mice, we show that co-activation of the two projections induces long-term potentiation (LTP) at vH-to-NAcSh synapses without affecting BLA-to-NAcSh synapses, revealing a heterosynaptic mechanism through which BLA signals persistently increase the temporally contingent vH-to-NAcSh transmission. Furthermore, this LTP is more prominent in dopamine D1 receptor-expressing (D1) MSNs than D2 MSNs and can be prevented by inhibition of either D1 receptors or dopaminergic terminals in NAcSh. This heterosynaptic LTP may provide a dopamine-guided mechanism through which vH-encoded cue inputs that are contingent to BLA activation acquire increased circuit representation to reinforce behavior. In motivated behaviors, environmental cues associated with arousing stimuli acquire increased incentive salience, processes mediated in part by the nucleus accumbens (NAc). NAc principal neurons receive glutamatergic projections from the ventral hippocampus (vH) and basolateral amygdala (BLA), which transmit information encoding contextual cues and affective states, respectively. Our results show that co-activation of the two projections induces long-term potentiation (LTP) at vH-to-NAc synapses without affecting BLA-to-NAc synapses, revealing a heterosynaptic mechanism through which BLA signals potentiate the temporally contingent vH-to-NAc transmission. Furthermore, this LTP is prevented by inhibition of either D1 receptors or dopaminergic axons. This heterosynaptic LTP may provide a dopamine-guided mechanism through which vH-encoded cue inputs that are contingent to BLA activation acquire increased circuit representation to reinforce behavior.
伏隔核壳（NAcSh）是一个关键的大脑区域，环境线索在这里获得激励显著性，从而加强动机行为。NAcSh 中的主要中间神经元（MSNs）接收来自边缘区域的广泛谷氨酸能投射，其中腹侧海马（vH）传递富含上下文线索的信息，而基底外侧杏仁核（BLA）编码实时唤醒状态。vH 和 BLA 向 NAcSh MSNs 汇聚投射，两者在与线索条件相关的动机行为上以时间锁定的方式被激活。在从雄性和雌性小鼠制备的脑片中，我们表明，这两个投射的共同激活会在 vH 到 NAcSh 突触处诱导长时程增强（LTP），而不会影响 BLA 到 NAcSh 突触，揭示了一种异突触机制，通过该机制，BLA 信号持续增加时间相关的 vH 到 NAcSh 传递。此外，这种 LTP 在多巴胺 D1 受体表达（D1）MSNs 中比 D2 MSNs 更为明显，并且可以通过抑制 NAcSh 中的 D1 受体或多巴胺能末梢来预防。这种异突触 LTP 可能提供了一种多巴胺指导的机制，通过该机制，与 BLA 激活相关的环境线索获得了增加的电路表示，以加强行为。在动机行为中，与唤醒刺激相关的环境线索获得了增加的激励显著性，这一过程部分由伏隔核（NAc）介导。NAc 主要神经元接收来自腹侧海马（vH）和基底外侧杏仁核（BLA）的谷氨酸能投射，分别传递编码上下文线索和情感状态的信息。我们的结果表明，这两个投射的共同激活会在 vH 到 NAc 突触处诱导长时程增强（LTP），而不会影响 BLA 到 NAc 突触，揭示了一种异突触机制，通过该机制，BLA 信号增强了时间相关的 vH 到 NAc 传递。此外，这种 LTP 可以通过抑制 D1 受体或多巴胺能轴突来预防。这种异突触 LTP 可能提供了一种多巴胺指导的机制，通过该机制，与 BLA 激活相关的 vH 编码线索输入获得了增加的电路表示，以加强行为。
