Reduced vocal variability in a zebra finch model of dopamine depletion: implications for Parkinson disease.
Reduced vocal variability in a zebra finch model of dopamine depletion: implications for Parkinson disease.
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DOI：
10.14814/phy2.12599
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发表时间：
2015-11
影响因子：
2.5
通讯作者：
White SA
中科院分区：
文献类型：
--
作者：
Miller JE;Hafzalla GW;Burkett ZD;Fox CM;White SA
中脑多巴胺（DA）调节基底神经节回路的活动，对多种物种的运动控制至关重要。在鸣禽中，DA是包括生殖驱动在内的动机行为的基础，并被认为是控制声音变化的神经活动的看门人。在斑胸草雀，Taeniopygia guttata，DA水平增加，在X区，一个专门的子区域的基底神经节，当一只雄鸟唱他的求爱歌，女性（女性导向; FD）。当他唱一个不那么刻板的版本时，水平保持稳定，这不是针对同种（无定向; UD）。在这里，我们使用了一个温和的剂量的神经毒素6-羟基多巴胺（6-OHDA），以减少突触前DA输入到X区，并表征了对FD和UD行为的影响。免疫印迹法用于定量酪氨酸羟化酶（TH）的水平作为生物标志物的DA传入损失的车辆和6-OHDA注射的鸟类。6-OHDA给药后，TH信号在X区较低，但在相邻的子区域腹侧纹状体苍白球（VSP）中不低。DA信号的突触后标记物在两个区域都没有变化。这些观察结果表明，影响是特定的发声基底神经节的突触前传入。同时，声乐变异性降低UD，但不FD歌曲。在帕金森病（PD）患者中观察到类似的声音变异性降低，但与DA损失的联系尚不清楚。6-OHDA鸣禽模型提供了一个独特的机会，以进一步研究如何DA损失皮质基底神经节通路影响发声控制。
Midbrain dopamine (DA) modulates the activity of basal ganglia circuitry important for motor control in a variety of species. In songbirds, DA underlies motivational behavior including reproductive drive and is implicated as a gatekeeper for neural activity governing vocal variability. In the zebra finch, Taeniopygia guttata, DA levels increase in Area X, a song-dedicated subregion of the basal ganglia, when a male bird sings his courtship song to a female (female-directed; FD). Levels remain stable when he sings a less stereotyped version that is not directed toward a conspecific (undirected; UD). Here, we used a mild dose of the neurotoxin 6-hydroxydopamine (6-OHDA) to reduce presynaptic DA input to Area X and characterized the effects on FD and UD behaviors. Immunoblots were used to quantify levels of tyrosine hydroxylase (TH) as a biomarker for DA afferent loss in vehicle- and 6-OHDA-injected birds. Following 6-OHDA administration, TH signals were lower in Area X but not in an adjacent subregion, ventral striatal-pallidum (VSP). A postsynaptic marker of DA signaling was unchanged in both regions. These observations suggest that effects were specific to presynaptic afferents of vocal basal ganglia. Concurrently, vocal variability was reduced during UD but not FD song. Similar decreases in vocal variability are observed in patients with Parkinson disease (PD), but the link to DA loss is not well-understood. The 6-OHDA songbird model offers a unique opportunity to further examine how DA loss in cortico-basal ganglia pathways affects vocal control.