Pluripotent stem cell derived inhibitory interneurons – principles and applications in health and disease
Francesca Keefe
Meng Li
摘要：Inhibitory interneurons are gamma-aminobutyric acid-ergic (GABAergic) nerve cells that act to maintain the appropriate excitation-inhibition bal-ance, and synchronise the output of principle cells to generate rhythmic patterns of firing (Kessaris et al., 2014). This critical role, along with their brain-wide distribution, has led to the implication of interneurons in many neuropathologies, including schizophrenia, autism, dystonia and epilepsies (Marín, 2012). This has in turn fuelled a growing interest into their inves-tigation. The molecular and functional heterogeneities within this class of neurons have resulted in a complex multifactorial classification system to assign interneurons into multiple subtypes (Figure 1A). Our journey to-wards understanding the interneuron diversity behind the classification sys-tem has brought to light the following principles. First, the subtype reflects the birthplace of the interneuron. Within the developing brain, inhibitory interneurons are born within focal regions, including the caudal and medial ganglionic eminences (CGE and MGE, respectively). Fate-mapping exper-iments in rodents demonstrated that calretinin (CR), vasoactive intestinal peptide and reelin positive interneurons are predominantly derived from CGE progenitors. Whereas, somatostatin (SST) and parvalbumin (PV) sub-types are MGE-derived, with an apparent SST: PV ratio shift along the MGE dorsoventral gradient (Kessaris et al., 2014). Second, interneuron subtypes exhibit differential vulnerability in neurological diseases (Marín, 2012). Third, there are brain region-specific differences in interneuron subtype composition, which are also species-dependent (Wu and Parent, 2000). The significance of these findings is unclear, as the manner to which interneuron lineages are determined by intrinsic and extrinsic cues remains under inves-tigation (Kessaris et al., 2014).
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论文发表日期：2020-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：2( 251-252 )