Graduate Program in Neurobiology, University of Washington, Seattle, Washington 98195, USA.
J Neurosci. 2010 Jan 20;30(3):1027-37. doi: 10.1523/JNEUROSCI.3585-09.2010.
Dopaminergic neurons in mammals respond to rewards and reward-predicting cues, and are thought to play an important role in learning actions or sensory cues that lead to reward. The anatomical sources of input that drive or modulate such responses are not well understood; these ultimately define the range of behavior to which dopaminergic neurons contribute. Primary rewards are not the immediate objective of all goal-directed behavior. For example, a goal of vocal learning is to imitate vocal-communication signals. Here, we demonstrate activation of dopaminergic neurons in songbirds driven by a basal ganglia region required for vocal learning, area X. Dopaminergic neurons in anesthetized zebra finches respond more strongly to the bird's own song (BOS) than to other sounds, and area X is critical for these responses. Direct pharmacological modulation of area X output, in the absence of auditory stimulation, is sufficient to bidirectionally modulate the firing rate of dopaminergic neurons. The only known pathway from song control regions to dopaminergic neurons involves a projection from area X to the ventral pallidum (VP), which in turn projects to dopaminergic regions. We show that VP neurons are spontaneously active and inhibited preferentially by BOS, suggesting that area X disinhibits dopaminergic neurons by inhibiting VP. Supporting this model, auditory-response latencies are shorter in area X than VP, and shorter in VP than dopaminergic neurons. Thus, dopaminergic neurons can be disinhibited selectively by complex sensory stimuli via input from the basal ganglia. The functional pathway we identify may allow dopaminergic neurons to contribute to vocal learning.
哺乳动物的多巴胺能神经元对奖励和奖励预测线索作出反应，被认为在学习导致奖励的行为或感觉线索方面发挥着重要作用。驱动或调节这种反应的输入的解剖学来源尚不清楚；这些最终定义了多巴胺能神经元所贡献的行为范围。主要奖励不是所有目标导向行为的直接目标。例如，声乐学习的目标是模仿声乐交流信号。在这里，我们证明了鸣禽中多巴胺能神经元的激活是由发声学习所必需的基底神经节区域（X 区）驱动的。在麻醉的斑马雀中，多巴胺能神经元对鸟类自身的歌声（BOS）的反应比其他声音更强，而 X 区对这些反应至关重要。在没有听觉刺激的情况下，直接对 X 区输出进行药理学调节足以双向调节多巴胺能神经元的放电率。已知的从歌唱控制区域到多巴胺能神经元的唯一途径涉及来自 X 区到腹侧苍白球（VP）的投射，而 VP 又投射到多巴胺能区域。我们表明，VP 神经元自发活动，并且优先被 BOS 抑制，这表明 X 区通过抑制 VP 来抑制多巴胺能神经元。支持该模型，X 区的听觉反应潜伏期比 VP 短，VP 比多巴胺能神经元短。因此，多巴胺能神经元可以通过来自基底神经节的输入选择性地被复杂的感觉刺激去抑制。我们确定的功能途径可能允许多巴胺能神经元为声乐学习做出贡献。
