Barrel cortex development lacks a key stage of hyperconnectivity from deep to superficial layers in a rat model of Absence Epilepsy

IF 6.7 2区 医学 Q1 NEUROSCIENCES Progress in Neurobiology Pub Date : 2024-01-19 DOI:10.1016/j.pneurobio.2023.102564
Simona Plutino , Emel Laghouati , Guillaume Jarre , Antoine Depaulis , Isabelle Guillemain , Ingrid Bureau
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Abstract

During development of the sensory cortex, the ascending innervation from deep to upper layers provides a temporary scaffold for the construction of other circuits that remain at adulthood. Whether an alteration in this sequence leads to brain dysfunction in neuro-developmental diseases remains unknown. Using functional approaches in a genetic model of Absence Epilepsy (GAERS), we investigated in barrel cortex, the site of seizure initiation, the maturation of excitatory and inhibitory innervations onto layer 2/3 pyramidal neurons and cell organization into neuronal assemblies. We found that cortical development in GAERS lacks the early surge of connections originating from deep layers observed at the end of the second postnatal week in normal rats and the concomitant structuring into multiple assemblies. Later on, at seizure onset (1 month old), excitatory neurons are hyper-excitable in GAERS when compared to Wistar rats. These findings suggest that early defects in the development of connectivity could promote this typical epileptic feature and/or its comorbidities.

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缺失性癫痫大鼠模型的桶状皮层发育缺乏从深层到浅层的超连接关键阶段
在感觉皮层的发育过程中,从深层到上层的上升神经支配为成年后其他回路的构建提供了一个临时支架。这一顺序的改变是否会导致神经发育疾病中的大脑功能障碍仍是未知数。我们在失神性癫痫遗传模型(GAERS)中使用功能方法,研究了桶状皮层(癫痫发作的起始部位)中第 2/3 层锥体神经元的兴奋性和抑制性神经支配的成熟过程,以及细胞组织成神经元集合的过程。我们发现,GAERS 的大脑皮层发育缺乏正常大鼠出生后第 2 周末期观察到的源自深层的早期连接激增以及随之而来的多集合结构。之后,在癫痫发作开始时(1 个月大),与 Wistar 大鼠相比,GAERS 的兴奋性神经元兴奋性过高。这些研究结果表明,连接性发育的早期缺陷可能会促进这种典型的癫痫特征和/或其合并症。
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来源期刊
Progress in Neurobiology
Progress in Neurobiology 医学-神经科学
CiteScore
12.80
自引率
1.50%
发文量
107
审稿时长
33 days
期刊介绍: Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.
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