Center for Neural Science, New York University, New York, New York 10003.
Center for Neural Science, New York University, New York, New York 10003
J Neurosci. 2018 Oct 17;38(42):9091-9104. doi: 10.1523/JNEUROSCI.1971-18.2018. Epub 2018 Sep 5.
The nucleus accumbens (NAc) is critical for motivated behavior and is rewired following exposure to drugs of abuse. Medium spiny neurons (MSNs) in the NAc express either D1 or D2 receptors and project to distinct downstream targets. Differential activation of these MSNs depends on both excitation from long-range inputs and inhibition via the local circuit. Assessing how long-range excitatory inputs engage inhibitory circuitry is therefore important for understanding NAc function. Here, we use slice electrophysiology and optogenetics to study ventral hippocampal (vHPC)-evoked feedforward inhibition in the NAc of male and female mice. We find that vHPC-evoked excitation is stronger at D1+ than D1- MSNs, whereas inhibition is unbiased at the two cell types. vHPC inputs contact both parvalbumin-positive (PV+) and somatostatin-positive (SOM+) interneurons, but PV+ cells are preferentially activated. Moreover, suppressing PV+ interneurons indicates they are primarily responsible for vHPC-evoked inhibition. Finally, repeated cocaine exposure alters the excitation of D1+ and D1- MSNs, without concomitant changes to inhibition, shifting the excitation/inhibition balance. Together, our results highlight the contributions of multiple interneuron populations to feedforward inhibition in the NAc. Moreover, they demonstrate that inhibition provides a stable backdrop on which drug-evoked changes to excitation occur within this circuit. Given the importance of the nucleus accumbens (NAc) in reward learning and drug-seeking behaviors, it is critical to understand what controls the activity of cells in this region. While excitatory inputs to projection neurons in the NAc have been identified, it is unclear how the local inhibitory network becomes engaged. Here, we identify a sparse population of interneurons responsible for feedforward inhibition evoked by ventral hippocampal input and characterize their connections within the NAc. We also demonstrate that the balance of excitation and inhibition that projection neurons experience is altered by exposure to cocaine. Together, this work provides insight into the fundamental circuitry of this region as well as the effects of drugs of abuse.
伏隔核（NAc）对于动机行为至关重要，并且在接触滥用药物后会被重新布线。NAc 中的中间神经元（MSNs）表达 D1 或 D2 受体，并投射到不同的下游靶点。这些 MSNs 的差异激活取决于来自长程输入的兴奋和通过局部回路的抑制。因此，评估长程兴奋性输入如何与抑制性回路相互作用对于理解 NAc 功能非常重要。在这里，我们使用切片电生理学和光遗传学研究了雄性和雌性小鼠 NAc 中腹侧海马（vHPC）诱发的前馈抑制。我们发现，vHPC 诱发的兴奋在 D1+MSNs 上比 D1-MSNs 更强，而抑制在两种细胞类型上是无偏的。vHPC 输入与 PV+和 SOM+中间神经元接触，但优先激活 PV+细胞。此外，抑制 PV+中间神经元表明它们主要负责 vHPC 诱发的抑制。最后，重复可卡因暴露改变了 D1+和 D1-MSNs 的兴奋，而抑制没有伴随变化，从而改变了兴奋/抑制平衡。总之，我们的研究结果强调了多个中间神经元群体对 NAc 中前馈抑制的贡献。此外，它们表明抑制为该回路中兴奋的药物诱发变化提供了稳定的背景。鉴于伏隔核（NAc）在奖励学习和觅药行为中的重要性，了解控制该区域细胞活动的因素至关重要。虽然已经确定了 NAc 中的投射神经元的兴奋性输入，但尚不清楚如何使局部抑制网络参与其中。在这里，我们确定了一个负责腹侧海马传入引起的前馈抑制的稀疏中间神经元群体，并描述了它们在 NAc 中的连接。我们还证明，可卡因暴露会改变投射神经元所经历的兴奋和抑制之间的平衡。总的来说，这项工作提供了对该区域基本回路以及滥用药物的影响的深入了解。
