NYU Neuroscience Institute, New York University Langone Medical Center New York, NY, USA.
Front Neural Circuits. 2012 Jul 9;6:44. doi: 10.3389/fncir.2012.00044. eCollection 2012.
Inhibitory neurons are critical for regulating effective transfer of sensory information and network stability. The precision of inhibitory function likely derives from the existence of a variety of interneuron subtypes. Their specification is largely dependent on the locale of origin of interneuron progenitors. Neocortical and hippocampal inhibitory neurons originate the subpallium, namely in the medial and caudal ganglionic eminences (MGE and CGE), and in the preoptic area (POA). In the hippocampus, neuronal nitric oxide synthase (nNOS)-expressing cells constitute a numerically large GABAergic interneuron population. On the contrary, nNOS-expressing inhibitory neurons constitute the smallest of the known neocortical GABAergic neuronal subtypes. The origins of most neocortical GABAergic neuron subtypes have been thoroughly investigated, however, very little is known about the origin of, or the genetic programs underlying the development of nNOS neurons. Here, we show that the vast majority of neocortical nNOS-expressing neurons arise from the MGE rather than the CGE. Regarding their molecular signature, virtually all neocortical nNOS neurons co-express the neuropeptides somatostatin (SST) and neuropeptide Y (NPY), and about half of them express the calcium-binding protein calretinin (CR). nNOS neurons thus constitute a small cohort of the MGE-derived SST-expressing population of cortical inhibitory neurons. Finally, we show that conditional removal of the transcription factor Sox6 in MGE-derived GABAergic cortical neurons results in an absence of SST and CR expression, as well as reduced expression of nNOS in neocortical nNOS neurons. Based on their respective abundance, origin and molecular signature, our results suggest that neocortical and hippocampal nNOS GABAergic neurons likely subserve different functions and have very different physiological relevance in these two cortical structures.
抑制性神经元对于调节感觉信息的有效传递和网络稳定性至关重要。抑制功能的精确性可能源于各种中间神经元亚型的存在。它们的特化在很大程度上取决于中间神经元祖细胞的起源部位。新皮层和海马的抑制性神经元起源于神经节隆起的内侧和尾侧部（MGE 和 CGE）和视前区（POA）。在海马体中，神经元型一氧化氮合酶（nNOS）表达细胞构成了一个数量庞大的 GABA 能中间神经元群体。相反，nNOS 表达的抑制性神经元构成了已知的最大的新皮层 GABA 能神经元亚型。大多数新皮层 GABA 能神经元亚型的起源已经得到了彻底的研究，然而，关于 nNOS 神经元的起源或发育背后的遗传程序知之甚少。在这里，我们表明，绝大多数新皮层 nNOS 表达神经元来自 MGE，而不是 CGE。就其分子特征而言，几乎所有新皮层 nNOS 神经元都共同表达神经肽 SST 和神经肽 Y（NPY），其中约一半表达钙结合蛋白 calretinin（CR）。因此，nNOS 神经元构成了源自 MGE 的 SST 表达皮质抑制神经元中的一小群。最后，我们表明，在源自 MGE 的 GABA 能皮质神经元中条件性去除转录因子 Sox6 会导致 SST 和 CR 表达缺失，以及新皮层 nNOS 神经元中 nNOS 表达减少。基于它们各自的丰度、起源和分子特征，我们的结果表明，新皮层和海马体的 nNOS GABA 能神经元可能具有不同的功能，并且在这两个皮质结构中具有非常不同的生理相关性。
