Rotaru Diana C, Barrionuevo German, Sesack Susan R
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Comp Neurol. 2005 Sep 26;490(3):220-38. doi: 10.1002/cne.20661.
The mediodorsal nucleus of the thalamus (MD) represents the main subcortical structure that projects to the prefrontal cortex (PFC) and it regulates key aspects of the cognitive functions of this region. Within the PFC, GABA local circuit neurons shape the activity patterns and hence the "memory fields" of pyramidal cells. Although the connections between the MD and PFC are well established, the ultrastructural relationships between projecting fibers from the MD and different subclasses of GABA cells in the PFC are not known. In order to address this issue in the rat, we examined MD axons labeled by tract-tracing in combination with immunogold-silver to identify different calcium-binding proteins localized within separate populations of interneurons. Electron micrographic examination of PFC sections from these animals revealed that MD terminals made primarily asymmetric synapses onto dendritic spines and less commonly onto dendritic shafts. Most of the dendrites receiving MD synaptic input were immunoreactive for parvalbumin (ParV), whereas MD synapses onto dendrites labeled for calretinin or calbindin were less frequent. We also observed that some MD terminals were themselves immunoreactive for calcium-binding proteins, again more commonly for ParV. These results suggest that the MD exerts a dual influence on PFC pyramidal cells: direct inputs onto spines and an indirect influence mediated via synapses onto each subclass of interneurons. The apparent preferential input to ParV cells endows MD afferents with a strong indirect inhibitory influence on pyramidal neuron activity by virtue of ParV cell synapses onto soma, proximal dendrites, and axon initial segments.
丘脑背内侧核（MD）是投射到前额叶皮质（PFC）的主要皮质下结构，它调节该区域认知功能的关键方面。在PFC内，GABA局部回路神经元塑造活动模式，从而塑造锥体细胞的“记忆场”。虽然MD和PFC之间的连接已得到充分证实，但MD投射纤维与PFC中不同亚类GABA细胞之间的超微结构关系尚不清楚。为了解决大鼠中的这个问题，我们结合免疫金银法检查了经束路追踪标记的MD轴突，以识别位于不同中间神经元群体内的不同钙结合蛋白。对这些动物的PFC切片进行电子显微镜检查发现，MD终末主要在树突棘上形成不对称突触，较少在树突干上形成突触。大多数接受MD突触输入的树突对小白蛋白（ParV）具有免疫反应性，而MD在标记有钙视网膜蛋白或钙结合蛋白的树突上形成的突触则较少见。我们还观察到一些MD终末本身对钙结合蛋白具有免疫反应性，同样更常见的是对ParV有反应。这些结果表明，MD对PFC锥体细胞有双重影响：直接输入到树突棘上，以及通过与每个中间神经元亚类的突触介导的间接影响。对ParV细胞的明显优先输入使MD传入纤维通过ParV细胞在胞体、近端树突和轴突起始段上的突触，对锥体细胞活动产生强烈的间接抑制作用。
