Dawitz Julia, Kroon Tim, Hjorth J J Johannes, Mansvelder Huib D, Meredith Rhiannon M
Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Front Cell Neurosci. 2020 Apr 21;14:91. doi: 10.3389/fncel.2020.00091. eCollection 2020.
The medial entorhinal cortex (MEC) contains specialized cell types whose firing is tuned to aspects of an animal's position and orientation in the environment, reflecting a neuronal representation of space. The spatially tuned firing properties of these cells quickly emerge during the third postnatal week of development in rodents. Spontaneous synchronized network activity (SSNA) has been shown to play a crucial role in the development of neuronal circuits prior to week 3. SSNA in MEC is well described in rodents during the first postnatal week, but there are little data about its development immediately prior to eye opening and spatial exploration. Furthermore, existing data lack single-cell resolution and are not integrated across layers. In this study, we addressed the question of whether the characteristics and underlying mechanisms of SSNA during the second postnatal week resemble that of the first week or whether distinct features emerge during this period. Using a combined calcium imaging and electrophysiology approach , we confirm that in mouse MEC during the second postnatal week, SSNA persists and in fact peaks, and is dependent on ionotropic glutamatergic signaling. However, SSNA differs from that observed during the first postnatal week in two ways: First, EC does not drive network activity in the hippocampus but only in neighboring neocortex (NeoC). Second, GABA does not drive network activity but influences it in a manner that is dependent both on age and receptor type. Therefore, we conclude that while there is a partial mechanistic overlap in SSNA between the first and second postnatal weeks, unique mechanistic features do emerge during the second week, suggestive of different or additional functions of MEC within the hippocampal-entorhinal circuitry with increasing maturation.
内侧内嗅皮层(MEC)包含特殊的细胞类型,其放电活动与动物在环境中的位置和方向相关,反映了空间的神经元表征。这些细胞的空间调谐放电特性在啮齿动物出生后的第三周迅速出现。自发同步网络活动(SSNA)已被证明在出生后第3周之前的神经元回路发育中起关键作用。MEC中的SSNA在出生后的第一周在啮齿动物中已有充分描述,但关于睁眼和空间探索前其发育的数据很少。此外,现有数据缺乏单细胞分辨率,且未跨层整合。在本研究中,我们探讨了出生后第二周SSNA的特征和潜在机制是否与第一周相似,或者在此期间是否出现不同特征的问题。使用钙成像和电生理学相结合的方法,我们证实,在出生后第二周的小鼠MEC中,SSNA持续存在且实际上达到峰值,并且依赖于离子型谷氨酸能信号传导。然而,SSNA在两个方面与出生后第一周观察到的情况不同:第一,内嗅皮层不驱动海马体中的网络活动,而仅驱动相邻新皮层(NeoC)中的网络活动。第二,GABA不驱动网络活动,但以依赖于年龄和受体类型的方式影响网络活动。因此,我们得出结论,虽然出生后第一周和第二周的SSNA在机制上存在部分重叠,但在第二周确实出现了独特的机制特征,这表明随着成熟度的增加,MEC在海马 - 内嗅皮层回路中具有不同或额外的功能。