Larimer Phillip, Spatazza Julien, Stryker Michael P, Alvarez-Buylla Arturo, Hasenstaub Andrea R
Center for Integrative Neuroscience, University of California, San Francisco, California.
Department of Neurology, University of California, San Francisco, California.
J Neurophysiol. 2017 Jul 1;118(1):131-139. doi: 10.1152/jn.00096.2017. Epub 2017 Mar 29.
Interneuron precursors transplanted into visual cortex induce network plasticity during their heterochronic maturation. Such plasticity can have a significant impact on the function of the animal and is normally present only during a brief critical period in early postnatal development. Elucidating the synaptic and physiological properties of interneuron precursors as they mature is key to understanding how long-term circuit changes are induced by transplants. We studied the development of transplant-derived interneurons and compared it to endogenously developing interneurons (those that are born and develop in the same animal) at parallel developmental time points, using patch-clamp recordings in acute cortical slices. We found that transplant-derived interneurons develop into fast-spiking and non-fast-spiking neurons characteristic of the medial ganglionic eminence (MGE) lineage. Transplant-derived interneurons matured more rapidly than endogenously developing interneurons, as shown by more hyperpolarized membrane potentials, smaller input resistances, and narrower action potentials at a juvenile age. In addition, transplant-derived fast-spiking interneurons have more quickly saturating input-output relationships and lower maximal firing rates in adulthood, indicating a possible divergence in function. Transplant-derived interneurons both form inhibitory synapses onto host excitatory neurons and receive excitatory synapses from host pyramidal cells. Unitary connection properties are similar to those of host interneurons. These transplant-derived interneurons, however, were less densely functionally connected onto host pyramidal cells than were host interneurons and received fewer spontaneous excitatory inputs from host cells. These findings suggest that many physiological characteristics of interneurons are autonomously determined, while some factors impacting their circuit function may be influenced by the environment in which they develop. Transplanting embryonic interneurons into older brains induces a period of plasticity in the recipient animal. We find that these interneurons develop typical fast-spiking and non-fast-spiking phenotypes by the end of adolescence. However, the input-output characteristics of transplant-derived neurons diverged from endogenously developing interneurons during adulthood, and they showed lower connection rates to local pyramidal cells at all time points. This suggests a unique and ongoing role of transplant-derived interneurons in host circuits, enabling interneuron transplant therapies.
移植到视觉皮层的中间神经元前体细胞在其异时成熟过程中诱导网络可塑性。这种可塑性会对动物的功能产生重大影响,且通常仅在出生后早期发育的短暂关键期出现。阐明中间神经元前体细胞成熟过程中的突触和生理特性是理解移植如何诱导长期电路变化的关键。我们研究了移植来源的中间神经元的发育,并在平行的发育时间点将其与内源性发育的中间神经元(即在同一动物体内产生和发育的中间神经元)进行比较,使用急性皮质切片中的膜片钳记录。我们发现,移植来源的中间神经元发育成具有内侧神经节隆起(MGE)谱系特征的快速发放和非快速发放神经元。移植来源的中间神经元比内源性发育的中间神经元成熟得更快,在幼年时表现为更超极化的膜电位、更小的输入电阻和更窄的动作电位。此外,移植来源的快速发放中间神经元在成年期具有更快饱和的输入-输出关系和更低的最大发放率,表明功能上可能存在差异。移植来源的中间神经元既在宿主兴奋性神经元上形成抑制性突触,也从宿主锥体细胞接收兴奋性突触。单突触连接特性与宿主中间神经元相似。然而,这些移植来源的中间神经元在功能上与宿主锥体细胞的连接密度低于宿主中间神经元,并且从宿主细胞接收的自发兴奋性输入较少。这些发现表明,中间神经元的许多生理特征是自主决定的,而一些影响其电路功能的因素可能受其发育环境的影响。将胚胎中间神经元移植到成年大脑中会在受体动物中诱导一段可塑性时期。我们发现,到青春期结束时,这些中间神经元会发育出典型的快速发放和非快速发放表型。然而,移植来源的神经元在成年期的输入-输出特征与内源性发育的中间神经元不同,并且在所有时间点与局部锥体细胞的连接率都较低。这表明移植来源的中间神经元在宿主电路中具有独特且持续的作用,为中间神经元移植治疗提供了可能。