Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, OX1 3TH Oxford, UK.
Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, OX1 3TH Oxford, UK.
Cell. 2019 Mar 7;176(6):1393-1406.e16. doi: 10.1016/j.cell.2018.12.037. Epub 2019 Feb 14.
Retrieving and acting on memories of food-predicting environments are fundamental processes for animal survival. Hippocampal pyramidal cells (PYRs) of the mammalian brain provide mnemonic representations of space. Yet the substrates by which these hippocampal representations support memory-guided behavior remain unknown. Here, we uncover a direct connection from dorsal CA1 (dCA1) hippocampus to nucleus accumbens (NAc) that enables the behavioral manifestation of place-reward memories. By monitoring neuronal ensembles in mouse dCA1→NAc pathway, combined with cell-type selective optogenetic manipulations of input-defined postsynaptic neurons, we show that dCA1 PYRs drive NAc medium spiny neurons and orchestrate their spiking activity using feedforward inhibition mediated by dCA1-connected parvalbumin-expressing fast-spiking interneurons. This tripartite cross-circuit motif supports spatial appetitive memory and associated NAc assemblies, being independent of dorsal subiculum and dispensable for both spatial novelty detection and reward seeking. Our findings demonstrate that the dCA1→NAc pathway instantiates a limbic-motor interface for neuronal representations of space to promote effective appetitive behavior.
检索和作用于预测食物环境的记忆是动物生存的基本过程。哺乳动物大脑中的海马锥体神经元(PYRs)提供了空间的记忆表现。然而,这些海马体表现支持记忆引导行为的基质仍然未知。在这里,我们发现了从背侧 CA1(dCA1)海马体到伏隔核(NAc)的直接连接,使位置奖励记忆的行为表现成为可能。通过监测小鼠 dCA1→NAc 通路中的神经元集合,结合对输入定义的突触后神经元进行细胞类型选择性光遗传学操作,我们表明 dCA1 PYRs 驱动 NAc 中间神经元,并使用由 dCA1 连接的表达 parvalbumin 的快速放电中间神经元介导的前馈抑制来协调其放电活动。这种三分交叉电路模式支持空间食欲记忆和相关的 NAc 集合,独立于背侧下托和对空间新颖性检测和奖励寻求都不是必需的。我们的发现表明,dCA1→NAc 通路为空间神经元表现建立了边缘-运动接口,以促进有效的食欲行为。