CART neurons in the lateral hypothalamus communicate with the nucleus accumbens shell via glutamatergic neurons in paraventricular thalamic nucleus to modulate reward behavior
CART neurons in the lateral hypothalamus communicate with the nucleus accumbens shell via glutamatergic neurons in paraventricular thalamic nucleus to modulate reward behavior
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DOI：
10.1007/s00429-017-1544-6
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发表时间：
2018-04-01
影响因子：
3.1
通讯作者：
Kokare, Dadasaheb M.
中科院分区：
文献类型：
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作者：
Choudhary, Amit G.;Somalwar, Amita R.;Kokare, Dadasaheb M.
丘脑室旁核（PVT）作为处理食物和药物相关奖励信息的中转节点，但其传入和传出尚未完全定义。我们测试了这样的假设：下丘脑外侧 (LH) 中的 CART 神经元投射到 PVT 神经元，PVT 神经元又通过谷氨酸能纤维与伏核壳 (AcbSh) 进行通信，伏核壳是奖励的典型部位。使用通过右侧 LH 内侧前脑束中的电极进行自我刺激的大鼠。 PVT 内给予 CART (55-102) 剂量依赖性（10-50 ng/大鼠）可降低颅内自刺激 (ICSS) 阈值并增加杠杆按压活动，表明肽的奖励促进作用。然而，用 CART 抗体（intra-PVT）或 MK-801（NMDA 拮抗剂，intra-AcbSh）治疗产生了相反的效果。亚有效剂量的MK-801（0.01μg/大鼠，AcbSh内）和有效剂量的CART（25ng/大鼠，PVT内）的组合减弱了CART的奖励作用。此外，我们筛选了 LH-PVT-AcbSh 回路，以了解调节体验引起的神经适应性变化。在 ICSS 植入电极同侧的 LH 中，我们注意到 CART mRNA 表达增加了两倍多。此外，条件化大鼠的 PVT 显示 (a) c-Fos 表达细胞和 CART 纤维末端以及 (b) CART 和囊泡谷氨酸转运蛋白 2 免疫染色元件明显增加。与此同时，AcbSh 显示 NMDA 受体亚基 NR1 的表达显着增加。我们认为 LH-PVT 中的 CART 和 PVT-AcbSh 回路中的谷氨酸可能支持自然条件下的食物寻找行为并存储奖励记忆。
Paraventricular thalamic nucleus (PVT) serves as a transit node processing food and drug-associated reward information, but its afferents and efferents have not been fully defined. We test the hypothesis that the CART neurons in the lateral hypothalamus (LH) project to the PVT neurons, which in turn communicate via the glutamatergic fibers with the nucleus accumbens shell (AcbSh), the canonical site for reward. Rats conditioned to self-stimulate via an electrode in the right LH-medial forebrain bundle were used. Intra-PVT administration of CART (55-102) dose-dependently (10-50 ng/rat) lowered intracranial self-stimulation (ICSS) threshold and increased lever press activity, suggesting reward-promoting action of the peptide. However, treatment with CART antibody (intra-PVT) or MK-801 (NMDA antagonist, intra-AcbSh) produced opposite effects. A combination of sub-effective dose of MK-801 (0.01 mu g/rat, intra-AcbSh) and effective dose of CART (25 ng/rat, intra-PVT) attenuated CART's rewarding action. Further, we screened the LH-PVT-AcbSh circuit for neuroadaptive changes induced by conditioning experience. A more than twofold increase was noticed in the CART mRNA expression in the LH on the side ipsilateral to the implanted electrode for ICSS. In addition, the PVT of conditioned rats showed a distinct increase in the (a) c-Fos expressing cells and CART fiber terminals, and (b) CART and vesicular glutamate transporter 2 immunostained elements. Concomitantly, the AcbSh showed a striking increase in expression of NMDA receptor subunit NR1. We suggest that CART in LH-PVT and glutamate in PVT-AcbSh circuit might support food-seeking behavior under natural conditions and also store reward memory.