Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons
Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons
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DOI：
10.1523/jneurosci.20-10-03864.2000
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发表时间：
2000-05-15
影响因子：
5.3
通讯作者：
Sesack, SR
中科院分区：
文献类型：
--
作者：
Carr, DB;Sesack, SR
前额叶皮层（PFC）向腹侧被盖区（VTA）的兴奋性投射在调节VTA神经元活动和前脑区多巴胺（DA）细胞外水平方面起着重要作用。以往的研究表明，PFC终末与腹侧被盖区DA和非DA神经元的树突形成突触。然而，这些细胞的投射目标是未知的。为了解决是否PFC传入神经支配不同群体的腹侧被盖区神经元的项目，以核延髓（NAc）或PFC，三重标记的方法，结合前包埋免疫金银标记的酪氨酸羟化酶（TH）或GABA的顺行和逆行追踪的过氧化物酶标记。在腹侧被盖区，PFC终端形成不对称的突触到树突状轴的TH或GABA的免疫反应。PFC终末也与从NAc或PFC逆行标记的VTA树突形成突触。从NAc逆行标记的树突和突触后至PFC传入纤维有时对GABA呈免疫反应性，但从未被TH标记。相反，树突逆行标记的PFC和突触后PFC传入的TH有时免疫反应，但从来没有GABA标记。这些结果提供了第一次证明PFC传入突触上确定的细胞群体中的腹侧被盖区，并表明了相当程度的特异性的PFC投射的目标。出乎意料的发现，选择性PFC突触输入到含有GABA的mesoporbens神经元和DA-含有mesocortical神经元表明新的机制，通过PFC可以影响活动的上升DA和GABA的预测。
Excitatory projections from the prefrontal cortex (PFC) to the ventral tegmental area (VTA) play an important role in regulating the activity of VTA neurons and the extracellular levels of dopamine (DA) within forebrain regions. Previous investigations have demonstrated that PFC terminals synapse on the dendrites of DA and non-DA neurons in the VTA. However, the projection targets of these cells are not known. To address whether PFC afferents innervate different populations of VTA neurons that project to the nucleus accumbens (NAc) or to the PFC, a triple labeling method was used that combined peroxidase markers for anterograde and retrograde tract-tracing with pre-embedding immunogold-silver labeling for either tyrosine hydroxylase (TH) or GABA. Within the VTA, PFC terminals formed asymmetric synapses onto dendritic shafts that were immunoreactive for either TH or GABA. PFC terminals also synapsed on VTA dendrites that were retrogradely labeled from the NAc or the PFC. Dendrites retrogradely labeled from the NAc and postsynaptic to PFC afferents were sometimes immunoreactive for GABA but were never TH-labeled. Conversely, dendrites retrogradely labeled from the PFC and postsynaptic to PFC afferents were sometimes immunoreactive for TH but were never GABA-labeled. These results provide the first demonstration of PFC afferents synapsing on identified cell populations in the VTA and indicate a considerable degree of specificity in the targets of the PFC projection. The unexpected finding of selective PFC synaptic input to GABA-containing mesoaccumbens neurons and DA-containing mesocortical neurons suggests novel mechanisms through which the PFC can influence the activity of ascending DA and GABA projections.