Modulation of Dopaminergic VTA Neurons by Urotensin II

腹侧被盖区神经元释放多巴胺的中脑边缘通路 (VTA)它投射到丘脑核（NAc），被认为在动机和奖励中起作用 流程.一些成瘾性药物通过增强中脑边缘系统对行为产生强有力的影响， 多巴胺活性腹侧被盖区神经元多巴胺的释放受多种因素和神经元的调节。 结构.向腹侧被盖区提供调节输入的一条通路起源于小脑延髓的中桥核。 脑干我们先前已经表明，中桥蛋白-VTA-NAc通路是由新的 神经肽尾加压素II（UII）。 为了促进我们的研究，我们已经开发并验证了白喉毒素与UN的融合物（Dtx-Uli）。这 毒素能够选择性地消融表达UII-R的中桥脑神经元，而不损伤 周围组织通过将这种毒素与微透析和行为模式相结合 （自我管理和条件性位置偏好），我们将确定Uil是否可以调节 强化行为。此外，为了更好地了解中桥核的功能，DTx-Uli将 用来切除这个区域的神经元随后，从不同方面提出了脑桥的功能， 将被测试（例如，前脉冲抑制，条件性位置偏爱）。 药物成瘾是一种多因素的疾病。这种异质性部分是由于遗传倾向。任何 一种在神经元回路中表达的基因，已知其调节 成瘾可能会影响成瘾的发展，尽管该基因可能不是成瘾的直接靶点。 流毒UIL是一种新兴的神经调质，可能与成瘾和发展有关。 上瘾的人此外，在其他工作中，联合国已被证明产生细胞重塑，这可能表明， 在神经可塑性中的作用。因此，未来的研究将包括调查Ull-R在 分子神经生物学变化和成瘾的发展。

The mesolimbic pathway through the release of dopamine from neurons in the ventral tegmental area (VTA), which project to the nucleus accumbens (NAc), is thought to have a role in motivation and reward processes. Some addictive drugs produce their potent effects on behavior by enhancing mesolimbic dopamine activity. Release of dopamine from VTA neurons is controlled by various factors and neuronal structures. One pathway providing regulatory input to the VTA originates in the mesopontine nuclei of the brainstem. We have previously shown that the mesopontine-VTA-NAc pathway is modulated by the novel neuropeptide urotensin II (Uil). To facilitate our studies we have developed and validated a fusion of diphtheria toxin with UN (Dtx-Uli). This toxin is able to selectively ablate Ull-R expressing neurons of the mesopontine without damage to surrounding tissue. Through the combination ofthis toxin with microdialysis and behavioral paradigms (self-administration and conditioned place preference), we will establish whether Uil can modulate reinforced behaviors. In addition, to better understand the function ofthe mesopontine nuclei, the Dtx-Uli will be used to ablate neurons of this region. Subsequently, different aspects of proposed mesopontine function will be tested ( ex. prepulse inhibition, conditioned place preference). Drug addiction is a multifactorial condition. This heterogeneity is partly due to genetic predisposition. Any gene that is expressed in the neuronal circuitry known to modulate the acquisition and maintenance of addiction could impact the development of an addiction, although that gene may not be the direct target of the drug. Uil is an emerging neuromodulator which may have implications in addiction and the development of addiction. Furthermore, in other work UN has been shown to produce cellular remolding, which may point to a role in neuroplasticity. Therefore, future studies will include the investigation ofthe role of Ull-R in molecular neurobiological changes and the development of addiction.