Mejias-Aponte Carlos A, Ye Changquan, Bonci Antonello, Kiyatkin Eugene A, Morales Marisela
Integrative Neuroscience Research Branch, Neuronal Networks Section.
Cellular Neurobiology Research Branch, Synaptic Physiology Section, and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Neurosci. 2015 Feb 4;35(5):1965-78. doi: 10.1523/JNEUROSCI.3422-13.2015.
Systemic administration of cocaine is thought to decrease the firing rates of ventral tegmental area (VTA) dopamine (DA) neurons. However, this view is based on categorizations of recorded neurons as DA neurons using preselected electrophysiological characteristics lacking neurochemical confirmation. Without applying cellular preselection, we recorded the impulse activity of VTA neurons in response to cocaine administration in anesthetized adult rats. The phenotype of recorded neurons was determined by their juxtacellular labeling and immunohistochemical detection of tyrosine hydroxylase (TH), a DA marker. We found that intravenous cocaine altered firing rates in the majority of recorded VTA neurons. Within the cocaine-responsive neurons, half of the population was excited and the other half was inhibited. Both populations had similar discharge rates and firing regularities, and most neurons did not exhibit changes in burst firing. Inhibited neurons were more abundant in the posterior VTA, whereas excited neurons were distributed evenly throughout the VTA. Cocaine-excited neurons were more likely to be excited by footshock. Within the subpopulation of TH-positive neurons, 36% were excited by cocaine and 64% were inhibited. Within the subpopulation of TH-negative neurons, 44% were excited and 28% were inhibited. Contrary to the prevailing view that all DA neurons are inhibited by cocaine, we found a subset of confirmed VTA DA neurons that is excited by systemic administration of cocaine. We provide evidence indicating that DA neurons are heterogeneous in their response to cocaine and that VTA non-DA neurons play an active role in processing systemic cocaine.
人们认为，可卡因的全身给药会降低腹侧被盖区（VTA）多巴胺（DA）神经元的放电频率。然而，这一观点是基于使用缺乏神经化学确认的预选电生理特征将记录的神经元分类为DA神经元。在未进行细胞预选的情况下，我们记录了麻醉成年大鼠中VTA神经元对可卡因给药的冲动活动。记录神经元的表型通过其近细胞标记和酪氨酸羟化酶（TH，一种DA标记物）的免疫组织化学检测来确定。我们发现静脉注射可卡因改变了大多数记录的VTA神经元的放电频率。在对可卡因有反应的神经元中，一半被兴奋，另一半被抑制。这两类神经元具有相似的放电率和放电规律，并且大多数神经元在爆发式放电方面没有表现出变化。抑制性神经元在VTA后部更为丰富，而兴奋性神经元则均匀分布于整个VTA。可卡因兴奋的神经元更有可能被足底电击所兴奋。在TH阳性神经元亚群中，36%被可卡因兴奋，64%被抑制。在TH阴性神经元亚群中，44%被兴奋，28%被抑制。与所有DA神经元都被可卡因抑制的普遍观点相反，我们发现了一组经确认的VTA DA神经元，它们在可卡因全身给药时被兴奋。我们提供的证据表明，DA神经元对可卡因的反应具有异质性，并且VTA非DA神经元在处理全身可卡因方面发挥着积极作用。
