Techniques that allow the manipulation of specific neural circuits have greatly increased in the past few years. DREADDs (Designer receptors exclusively activated by designer drugs) provide an elegant way to manipulate individual brain structures and/or neural circuits, including neuromodulatory pathways. Considerable efforts have been made to increase cell-type specificity of DREADD expression while decreasing possible limitations due to multiple viral vectors injections. In line with this, a retrograde canine adenovirus type 2 (CAV-2) vector carrying a Cre-dependent DREADD cassette has been recently developed. In combination with Cre-driver transgenic animals, the vector allows one to target neuromodulatory pathways with cell-type specificity. In the present study, we specifically targeted catecholaminergic pathways by injecting the vector in knock-in rat line containing Cre recombinase cassette under the control of the tyrosine hydroxylase promoter. We assessed the efficacy of infection of the nigrostriatal pathway and the catecholaminergic pathways ascending to the orbitofrontal cortex (OFC) and found cell-type-specific DREADD expression.

在过去的几年中，允许操纵特定神经回路的技术已大大增加。DREADD（被设计药物独家激活的设计受体）提供了一种优雅的方式来操纵单个大脑的结构和/或神经回路，包括神经调节途径。为了增加DREADD表达的细胞类型特异性，同时减少了由于多次病毒载体注射而引起的可能的限制，已经做出了相当大的努力。与此相符，最近已经开发了带有Cre依赖性DREADD盒的逆行2型犬腺病毒（CAV-2）载体。与Cre-driver转基因动物组合后，该载体可使人以细胞类型特异性靶向神经调节途径。在目前的研究中，我们通过在酪氨酸羟化酶启动子的控制下将载体注入含有Cre重组酶盒的敲入大鼠品系中，从而专门针对儿茶酚胺能途径。我们评估了黑质纹状体途径和儿茶酚胺能途径感染升至眶额叶皮层（OFC）的感染功效，并发现了细胞类型特异性DREADD表达。