Intramural Research Program, National Institute on Drug Abuse, National Institute on Health, Baltimore, MD, USA.
Neuropsychopharmacology. 2018 Mar;43(4):680-689. doi: 10.1038/npp.2017.228. Epub 2017 Oct 6.
Brain stimulation has identified two central subsets of stimulation sites with motivational relevance. First, there is a large and disperse set of sites where stimulation is reinforcing, increasing the frequency of the responses it follows, and second, a much more restricted set of sites where-along with reinforcement-stimulation also has drive-like effects, instigating feeding, copulation, predation, and other motivated acts in otherwise sated or peaceful animals. From this work a dispersed but synaptically interconnected network of reinforcement circuitry is emerging: it includes afferents to the ventral tegmental area and substantia nigra; the dopamine systems themselves; glutamatergic afferents to the striatum; and one of two dopamine-receptor-expressing efferent pathways of the striatum. Stimulation of a limited subset of these sites, including descending inhibitory medial forebrain bundle fibers, induces both feeding and reinforcement, and suggests the possibility of a subset of fibers where stimulation has both drive-like and reinforcing effects. This review stresses the common findings of sites and connectivity between electrical and optogenetic studies of core drive and reinforcement sites. By doing so, it suggests the biological importance of optogenetic follow-up of less-publicized electrical stimulation findings. Such studies promise not only information about origins, neurotransmitters, and connectivity of related networks, by covering more sensory and at least one putative motor component they also promote a much deeper understanding of the breadth of motivational function.
脑刺激已经确定了与动机相关的两个具有刺激作用的核心子集。首先,有一个很大且分散的刺激部位集合,刺激会增强它所跟随的反应频率;其次,还有一个更为局限的部位集合,刺激除了具有增强作用外,还具有类似驱动力的效应,激发进食、交配、捕食和其他在原本满足或平静的动物中产生的受驱动的行为。从这项工作中,一个分散但突触互联的强化回路网络正在浮现:它包括腹侧被盖区和黑质的传入神经;多巴胺系统本身;纹状体的谷氨酸能传入神经;以及纹状体中两种多巴胺受体表达的传出途径之一。刺激这些部位的有限子集,包括下行抑制性内侧前脑束纤维,会同时诱导进食和增强作用,并提示刺激具有类似驱动力和增强作用的纤维子集的可能性。这篇综述强调了核心驱动和强化部位的电刺激和光遗传学研究之间的共同发现的部位和连接性。这样做,它表明了对光遗传学方法跟进未被广泛报道的电刺激发现的生物学重要性。这些研究不仅有望提供有关相关网络起源、神经递质和连接性的信息,而且通过涵盖更多的感觉至少一个假定的运动成分,还促进了对动机功能广度的更深入理解。