Institut de Neurobiologie de la Méditerranée INMED, Institut National de la Santé et de la Recherche Médicale INSERM U1249, 13273 Marseille, France.
Aix-Marseille University, 13273 Marseille, France.
J Neurosci. 2020 Jan 29;40(5):1028-1041. doi: 10.1523/JNEUROSCI.1100-19.2019. Epub 2019 Dec 12.
The nucleus accumbens (NAc) is a mesocorticolimbic structure that integrates cognitive, emotional and motor functions. Although its role in psychiatric disorders is widely acknowledged, the understanding of its circuitry is not complete. Here, we combined optogenetic and whole-cell recordings to draw a functional portrait of excitatory disambiguated synapses onto D1 and D2 medium spiny neurons (MSNs) in the adult male mouse NAc core. Comparing synaptic properties of ventral hippocampus (vHipp), basolateral amygdala (BLA) and prefrontal cortex (PFC) inputs revealed a hierarchy of synaptic inputs that depends on the identity of the postsynaptic target MSN. Thus, the BLA is the dominant excitatory pathway onto D1 MSNs (BLA > PFC = vHipp) while PFC inputs dominate D2 MSNs (PFC > vHipp > BLA). We also tested the hypothesis that endocannabinoids endow excitatory circuits with pathway- and cell-specific plasticity. Thus, whereas CB1 receptors (CB1R) uniformly depress excitatory pathways regardless of MSNs identity, TRPV1 receptors (TRPV1R) bidirectionally control inputs onto the NAc core in a pathway-specific manner. Finally, we show that the interplay of TRPV1R/CB1R shapes plasticity at BLA-NAc synapses. Together these data shed new light on synapse and circuit specificity in the adult NAc core and illustrate how endocannabinoids contribute to pathway-specific synaptic plasticity. We examined the impact of connections from the ventral hippocampus (vHipp,) basolateral amygdala (BLA) and prefrontal cortex (PFC) onto identified medium spiny neurons (MSNs) in the adult accumbens core. We found BLA inputs were strongest at D1 MSNs while PFC inputs dominate D2 MSNs. Pathway- and cell-specific circuit control was also facilitated by endocannabinoids that endow bidirectional synaptic plasticity at identified BLA-NAc synapses. These data provide mechanistic insights on synapse and circuit specificity in the adult NAc core.
伏隔核(NAc)是一个边缘皮质和边缘皮质结构,整合认知、情感和运动功能。尽管它在精神疾病中的作用得到广泛认可,但对其电路的理解并不完整。在这里,我们结合光遗传学和全细胞膜片钳记录技术,绘制了成年雄性小鼠 NAc 核心中兴奋性分离突触投射到 D1 和 D2 中间神经元(MSNs)的功能图谱。比较腹侧海马(vHipp)、基底外侧杏仁核(BLA)和前额叶皮层(PFC)输入的突触特性,揭示了一个依赖于突触后靶标 MSN 身份的突触输入层次结构。因此,BLA 是 D1 MSNs 的主要兴奋性通路(BLA > PFC = vHipp),而 PFC 输入则支配 D2 MSNs(PFC > vHipp > BLA)。我们还测试了内源性大麻素赋予兴奋性回路以通路和细胞特异性可塑性的假设。因此,尽管 CB1 受体(CB1R)均匀地抑制无论 MSN 身份如何的兴奋性通路,但 TRPV1 受体(TRPV1R)以通路特异性的方式双向控制 NAc 核心的输入。最后,我们表明 TRPV1R/CB1R 的相互作用塑造了 BLA-NAc 突触的可塑性。这些数据为成年 NAc 核心中的突触和电路特异性提供了新的认识,并说明了内源性大麻素如何促进通路特异性突触可塑性。我们研究了来自腹侧海马(vHipp)、基底外侧杏仁核(BLA)和前额叶皮层(PFC)的连接对成年伏隔核核心中鉴定的中间神经元(MSNs)的影响。我们发现 BLA 输入在 D1 MSNs 最强,而 PFC 输入则支配 D2 MSNs。内源性大麻素也促进了通路特异性的电路控制,赋予了鉴定的 BLA-NAc 突触的双向突触可塑性。这些数据提供了关于成年 NAc 核心中突触和电路特异性的机制见解。
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