Department of Psychiatry and NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY, USA.
Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
Neuropsychopharmacology. 2019 Sep;44(10):1828-1836. doi: 10.1038/s41386-019-0396-6. Epub 2019 Apr 20.
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway has recently been implicated in the suppression of fear memory. A notable feature of this pathway is the corelease of neurotransmitters and neuropeptides from MHb neurons. Our studies in mice reveal that an activation of substance P-positive dorsomedial habenula (dMHb) neurons results in simultaneous release of glutamate and glycine in the lateral interpeduncular nucleus (LIPN). This glycine receptor activity inhibits an activity-dependent long-lasting potentiation of glutamatergic synapses in LIPN neurons, while substance P enhances this plasticity. An endocannabinoid CB1 receptor-mediated suppression of GABA receptor activity allows substance P to induce a long-lasting increase in glutamate release in LIPN neurons. Consistent with the substance P-dependent synaptic potentiation in the LIPN, the NK1R in the IPN is involved in fear extinction but not fear conditioning. Thus, our study describes a novel plasticity mechanism in the LIPN and a region-specific role of substance P in fear extinction.
中脑内侧缰核-脚间核（MHb-IPN）通路最近被牵涉到恐惧记忆的抑制中。该通路的一个显著特点是从中脑缰核神经元共同释放神经递质和神经肽。我们在小鼠中的研究表明，激活含有 P 物质的中脑背内侧缰核（dMHb）神经元会导致谷氨酸和甘氨酸在外侧脚间核（LIPN）中同时释放。这种甘氨酸受体活性抑制 LIPN 神经元中谷氨酸能突触的活动依赖性长时程增强，而 P 物质增强了这种可塑性。内源性大麻素 CB1 受体介导的 GABA 受体活性抑制允许 P 物质诱导 LIPN 神经元中谷氨酸释放的持久增加。与 LIPN 中的 P 物质依赖性突触增强一致，IPN 中的 NK1R 参与了恐惧消退而不是恐惧条件反射。因此，我们的研究描述了 LIPN 中的一种新的可塑性机制以及 P 物质在恐惧消退中的特定区域作用。
