Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; email:
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts 02142, USA.
Annu Rev Neurosci. 2020 Jul 8;43:1-30. doi: 10.1146/annurev-neuro-070918-050421. Epub 2019 Jul 12.
Cortical interneurons display striking differences in shape, physiology, and other attributes, challenging us to appropriately classify them. We previously suggested that interneuron types should be defined by their role in cortical processing. Here, we revisit the question of how to codify their diversity based upon their division of labor and function as controllers of cortical information flow. We suggest that developmental trajectories provide a guide for appreciating interneuron diversity and argue that subtype identity is generated using a configurational (rather than combinatorial) code of transcription factors that produce attractor states in the underlying gene regulatory network. We present our updated three-stage model for interneuron specification: an initial cardinal step, allocating interneurons into a few major classes, followed by definitive refinement, creating subclasses upon settling within the cortex, and lastly, state determination, reflecting the incorporation of interneurons into functional circuit ensembles. We close by discussing findings indicating that major interneuron classes are both evolutionarily ancient and conserved. We propose that the complexity of cortical circuits is generated by phylogenetically old interneuron types, complemented by an evolutionary increase in principal neuron diversity. This suggests that a natural neurobiological definition of interneuron types might be derived from a match between their developmental origin and computational function.
皮质中间神经元在形态、生理和其他属性上表现出显著差异，这使得我们难以对其进行适当分类。我们之前曾提出，中间神经元的类型应该根据其在皮质处理中的作用来定义。在这里，我们重新审视了如何根据其作为皮质信息流控制器的分工和功能来对其多样性进行编码的问题。我们认为，发育轨迹为理解中间神经元的多样性提供了指导，并认为亚型身份是使用转录因子的组合（而不是组合）代码产生的，该代码在基础基因调控网络中产生吸引状态。我们提出了我们更新的中间神经元指定的三阶段模型：初始关键步骤，将中间神经元分配到少数几个主要类别中，然后进行明确的细化，在皮层内定居后创建子类，最后是状态确定，反映了中间神经元纳入功能回路集合。最后，我们讨论了表明主要中间神经元类在进化上是古老且保守的发现。我们提出，皮质回路的复杂性是由进化上古老的中间神经元类型产生的，而主要神经元多样性的进化增加则是其补充。这表明，中间神经元类型的自然神经生物学定义可能源于其发育起源和计算功能之间的匹配。
