Wester Jason C, McBain Chris J
Program in Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland 20892.
Program in Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland 20892
J Neurosci. 2016 Mar 2;36(9):2646-62. doi: 10.1523/JNEUROSCI.4000-15.2016.
Spontaneously generated network activity is a hallmark of developing neural circuits, and plays an important role in the formation of synaptic connections. In the rodent hippocampus, this activity is observed in vitro as giant depolarizing potentials (GDPs) during the first postnatal week. Interneurons importantly contribute to GDPs, due to the depolarizing actions of GABA early in development. While they are highly diverse, cortical interneurons can be segregated into two distinct groups based on their embryonic lineage from either the medial or caudal ganglionic eminences (MGE and CGE). There is evidence suggesting CGE-derived interneurons are important for GDP generation; however, their contribution relative to those from the MGE has never been directly tested. Here, we optogenetically inhibited either MGE- or CGE-derived interneurons in a region-specific manner in mouse neonatal hippocampus in vitro. In CA1, where interneurons are the primary source of recurrent excitation, we found that those from the MGE strongly and preferentially contributed to GDP generation. Furthermore, in dual whole-cell patch recordings in neonatal CA1, MGE interneurons formed synaptic connections to and from neighboring pyramidal cells at a much higher rate than those from the CGE. These MGE interneurons were commonly perisomatic targeting, in contrast to those from the CGE, which were dendrite targeting. Finally, inhibiting MGE interneurons in CA1 suppressed GDPs in CA3 and vice versa; conversely, they could also trigger GDPs in CA1 that propagated to CA3 and vice versa. Our data demonstrate a key role for MGE-derived interneurons in both generating and coordinating GDPs across the hippocampus.
During nervous system development, immature circuits internally generate rhythmic patterns of electrical activity that promote the establishment of synaptic connections. Immature interneurons are excitatory rather than inhibitory and actively contribute to the generation of these spontaneous network events, referred to as giant depolarizing potentials (GDPs) in the hippocampus. Interneurons can be generally separated into two distinct groups based on their origin in the embryo from the medial or caudal ganglionic eminences (MGE and CGE). Here we show that MGE interneurons play a dominant role in generating GDPs compared with their CGE counterparts. They accomplish this due to their high synaptic connectivity within the local circuitry. Finally, they can control network activity across large regions of the developing hippocampus.
自发产生的网络活动是发育中神经回路的一个标志，并且在突触连接的形成中起重要作用。在啮齿动物海马体中，这种活动在出生后第一周的体外培养中表现为巨大去极化电位（GDPs）。由于发育早期GABA的去极化作用，中间神经元对GDPs有重要贡献。虽然皮质中间神经元高度多样化，但根据其胚胎起源于内侧或尾侧神经节隆起（MGE和CGE），可将其分为两个不同的组。有证据表明源自CGE的中间神经元对GDP的产生很重要；然而，它们相对于源自MGE的中间神经元的贡献从未被直接测试过。在这里，我们在体外以区域特异性方式用光遗传学方法抑制小鼠新生海马体中源自MGE或CGE的中间神经元。在CA1区，中间神经元是反复兴奋的主要来源，我们发现源自MGE的中间神经元对GDP的产生有强烈且优先的贡献。此外，在新生CA1区的双细胞全细胞膜片钳记录中，MGE中间神经元与相邻锥体细胞之间形成突触连接的速率比源自CGE的中间神经元高得多。与源自CGE的中间神经元（靶向树突）不同，这些MGE中间神经元通常靶向胞体周围。最后，抑制CA1区的MGE中间神经元会抑制CA3区的GDPs，反之亦然；相反，它们也可以在CA1区触发传播到CA3区的GDPs，反之亦然。我们的数据证明了源自MGE的中间神经元在整个海马体中产生和协调GDPs方面的关键作用。
在神经系统发育过程中，未成熟的神经回路在内部产生有节律的电活动模式，促进突触连接的建立。未成熟的中间神经元是兴奋性的而非抑制性的，并积极参与这些自发网络事件的产生，在海马体中这些事件被称为巨大去极化电位（GDPs）。根据中间神经元在胚胎中的起源于内侧或尾侧神经节隆起（MGE和CGE），它们通常可分为两个不同的组。在这里我们表明，与源自CGE的中间神经元相比，源自MGE的中间神经元在产生GDPs方面起主导作用。它们之所以能做到这一点，是因为它们在局部回路中具有高度的突触连接性。最后，它们可以控制发育中的海马体大片区域的网络活动。
