Vandecasteele Marie, Glowinski Jacques, Deniau Jean-Michel, Venance Laurent
Université Pierre et Marie Curie, Paris 75005, France.
Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4904-9. doi: 10.1073/pnas.0703121105. Epub 2008 Mar 17.
Midbrain dopaminergic (DAergic) neurons play a major regulatory role in in goal-directed behavior and reinforcement learning. DAergic neuron activity, and therefore spatiotemporal properties of dopamine release, precisely encodes reward signals. Neuronal activity is shaped both by external afferences and local interactions (chemical and electrical transmissions). Numerous hints suggest the existence of chemical interactions between DAergic neurons, but direct evidence and characterization are still lacking. Here, we show, using dual patch-clamp recordings in rat brain slices, a widespread bidirectional chemical transmission between DAergic neuron pairs. Hyperpolarizing postsynaptic potentials were partially mediated by D2-like receptors, and entirely resulted from the inhibition of the hyperpolarization-activated depolarizing current (Ih). These results constitute the first evidence in paired recordings of a chemical transmission relying on conductance decrease in mammals. In addition, we show that chemical transmission and electrical synapses frequently coexist within the same neuron pair and dynamically interact to shape DAergic neuron activity.
中脑多巴胺能(DAergic)神经元在目标导向行为和强化学习中起主要调节作用。多巴胺能神经元活动以及由此产生的多巴胺释放的时空特性精确地编码奖励信号。神经元活动受外部传入和局部相互作用(化学和电传递)的影响。大量线索表明多巴胺能神经元之间存在化学相互作用,但仍缺乏直接证据和特征描述。在这里,我们使用大鼠脑片的双膜片钳记录表明,多巴胺能神经元对之间存在广泛的双向化学传递。超极化突触后电位部分由D2样受体介导,完全是由超极化激活的去极化电流(Ih)的抑制引起的。这些结果构成了哺乳动物中依赖电导降低的化学传递配对记录的首个证据。此外,我们表明化学传递和电突触经常共存于同一神经元对中,并动态相互作用以塑造多巴胺能神经元活动。