Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2011 Aug 10;31(32):11457-71. doi: 10.1523/JNEUROSCI.1384-11.2011.
Lateral habenula (LHb) neurons signal negative "reward-prediction errors" and inhibit midbrain dopamine (DA) neurons. Yet LHb neurons are largely glutamatergic, indicating that this inhibition may occur through an intermediate structure. Recent studies in rats have suggested a candidate for this role, the GABAergic rostromedial tegmental nucleus (RMTg), but this neural pathway has not yet been tested directly. We now show using electrophysiology and anatomic tracing that (1) the monkey has an inhibitory structure similar to the rat RMTg; (2) RMTg neurons receive excitatory input from the LHb, exhibit negative reward-prediction errors, and send axonal projections near DA soma; and (3) stimulating this structure inhibits DA neurons. Surprisingly, some RMTg neurons responded to reward cues earlier than the LHb, and carry "state-value" signals not found in DA neurons. Thus, our data suggest that the RMTg translates LHb reward-prediction errors (negative) into DA reward-prediction errors (positive), while transmitting additional motivational signals to non-DA networks.
外侧缰核 (LHb) 神经元传递负的“奖赏预测误差”信号，并抑制中脑多巴胺 (DA) 神经元。然而，LHb 神经元主要是谷氨酸能的，这表明这种抑制可能通过中间结构发生。最近在大鼠中的研究提出了这个作用的一个候选结构，即 GABA 能的穹隆脚被盖网状核（RMTg），但这个神经通路尚未被直接测试。我们现在使用电生理学和解剖追踪显示：（1）猴子具有类似于大鼠 RMTg 的抑制性结构；（2）RMTg 神经元接收来自 LHb 的兴奋性输入，表现出负的奖赏预测误差，并在 DA 神经元体附近发送轴突投射；（3）刺激该结构抑制 DA 神经元。令人惊讶的是，一些 RMTg 神经元对奖赏线索的反应早于 LHb，并传递 DA 神经元中未发现的“状态价值”信号。因此，我们的数据表明，RMTg 将 LHb 的奖赏预测误差（负）转化为 DA 的奖赏预测误差（正），同时将额外的动机信号传递给非 DA 网络。
