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首页> 外文期刊>The European Journal of Neuroscience >Hypocretin /orexin preferentially activates caudomedial ventral tegmental area dopamine neurons.
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Hypocretin /orexin preferentially activates caudomedial ventral tegmental area dopamine neurons.

机译：降钙素/肾上腺素优先激活腹内侧腹盖区多巴胺神经元。

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摘要

The hypocretin/orexin (HCRT) neuropeptide system modulates behavioral state and state-dependent processes via actions on multiple neuromodulatory transmitter systems. Recent studies indicate that HCRT selectively increases dopamine (DA) neurotransmission within the prefrontal cortex (PFC) and the shell subregion of the nucleus accumbens (NAs), but not the core subregion of the nucleus accumbens (NAc). The circuitry underlying the differential actions of HCRT across distinct DA systems is unclear. The current study examined whether HCRT preferentially activates PFC- and NAs-projecting relative to NAc-projecting DA neurons within the VTA. One week after infusion of the retrograde tracer fluorogold (FG) into the medial PFC, NAc or NAs, animals received a ventricular infusion of HCRT-1. Subsequent analyses conducted across the rostral-caudal extent of the VTA determined the degree to which: (i) Fos-immunoreactivity (ir) was observed within tyrosine hydroxylase (TH)-ir neurons; (ii) TH-ir was observed within FG-ir neurons; and (iii) Fos-ir was observed within FG-ir neurons. HCRT significantly increased Fos-ir in VTA DA (TH-ir) neurons, primarily in a restricted population of small-to-medium-sized DA neurons located within the caudomedial VTA. Furthermore, within this region of the VTA, PFC- and NAs-projecting TH-ir neurons were more likely to contain Fos-ir than were NAc-projecting TH-ir neurons. These results provide novel evidence that HCRT selectively activates PFC- and NAs-projecting DA neurons within the VTA, and suggest a potential role for HCRT in PFC- and NAs-dependent cognitive and/or affective processes. Moreover, these and other observations suggest that the dysregulation of HCRT-DA interactions could contribute to cognitive/affective dysfunction associated with a variety of behavioral disorders.
机译：降钙素/肾上腺素（HCRT）神经肽系统通过对多个神经调节递质系统的作用来调节行为状态和依赖状态的过程。最近的研究表明，HCRT有选择地增加前额叶皮层（PFC）和伏隔核（NAs）的壳子区域内的多巴胺（DA）神经传递，但不增加伏隔核（NAc）的核心子区域。跨不同DA系统的HCRT的不同动作所依据的电路尚不清楚。本研究检查了HCRT是否相对于VTA中的NAc投射DA神经元优先激活PFC和NAs投射。向内侧PFC，NAc或NAs输注逆行示踪剂氟金（FG）一星期后，动物接受了HCRT-1的心室输注。随后对VTA的尾状范围进行了分析，确定了以下程度：（i）在酪氨酸羟化酶（TH）-ir神经元中观察到Fos免疫反应性（ir）; （ii）在FG-ir神经元内观察到TH-ir; （iii）在FG-ir神经元内观察到Fos-ir。 HCRT显着增加了VTA DA（TH-ir）神经元中的Fos-ir，主要是位于颞内侧VTA内的中小型DA神经元的受限制群体中。此外，在VTA的这一区域内，投射PFC和NAs的TH-ir神经元比投射NAc的TH-ir神经元更可能含有Fos-ir。这些结果提供了新的证据，表明HCRT在VTA内选择性激活PFC和NAs投射的DA神经元，并暗示HCRT在PFC和NAs依赖性认知和/或情感过程中的潜在作用。而且，这些和其他观察结果表明，HCRT-DA相互作用的失调可能导致与多种行为障碍相关的认知/情感功能障碍。

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