Lassen Matthew B, Brown J Elliott, Stobbs Sarah H, Gunderson Seth H, Maes Levi, Valenzuela C Fernando, Ray Andrew P, Henriksen Steven J, Steffensen Scott C
Brigham Young University, Provo, UT 84602, USA.
Brain Res. 2007 Jul 2;1156:46-58. doi: 10.1016/j.brainres.2007.04.053. Epub 2007 Apr 25.
The neural substrate of brain stimulation reward (BSR) has eluded identification since its discovery more than a half-century ago. Notwithstanding the difficulties in identifying the neuronal integrator of BSR, the mesocorticolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) of the midbrain has been implicated. We have previously demonstrated that the firing rate of a subpopulation of gamma-aminobutyric acid (GABA) neurons in the VTA increases in anticipation of BSR. We show here that GABA neurons in the VTA, midbrain, hypothalamus, and thalamus of rats express connexin-36 (Cx36) gap junctions (GJs) and couple electrically upon DA application or by stimulation of the internal capsule (IC), which also supports self-stimulation. The threshold for responding for IC self-stimulation was the threshold for electrical coupling between GABA neurons, the degree of responding for IC self-stimulation was proportional to the magnitude of electrical coupling between GABA neurons, and GJ blockers increased the threshold for IC self-stimulation without affecting performance. Thus, a network of electrically coupled GABA neurons in the ventral brain may form the elusive neural integrator of BSR.
自半个多世纪前发现脑刺激奖赏（BSR）以来，其神经基质一直未被确定。尽管确定BSR的神经元整合器存在困难，但起源于中脑腹侧被盖区（VTA）的中脑皮质边缘多巴胺（DA）系统被认为与之有关。我们之前已经证明，在预期BSR时，VTA中γ-氨基丁酸（GABA）神经元亚群的放电率会增加。我们在此表明，大鼠VTA、中脑、下丘脑和丘脑的GABA神经元表达连接蛋白36（Cx36）间隙连接（GJ），并且在应用DA或刺激内囊（IC）时会发生电耦合，而刺激内囊也支持自我刺激。IC自我刺激的反应阈值是GABA神经元之间电耦合的阈值，IC自我刺激的反应程度与GABA神经元之间电耦合的大小成正比，并且GJ阻滞剂会提高IC自我刺激的阈值而不影响行为表现。因此，腹侧脑中电耦合的GABA神经元网络可能构成了难以捉摸的BSR神经整合器。
