Astrocytes of the early postnatal brain

Abstract

In the rodent forebrain, the majority of astrocytes are generated during the early postnatal phase. Following differentiation, astrocytes undergo maturation which accompanies the development of the neuronal network. Neonate astrocytes exhibit a distinct morphology and domain size which differs to their mature counterparts. Moreover, many of the plasma membrane proteins prototypical for fully developed astrocytes are only expressed at low levels at neonatal stages. These include connexins and Kir4.1, which define the low membrane resistance and highly negative membrane potential of mature astrocytes. Newborn astrocytes moreover express only low amounts of GLT-1, a glutamate transporter critical later in development.Furthermore, they show specific differences in the properties and spatio-temporal pattern of intracellular calcium signals, resulting from differences in their repertoire of receptors and signalling pathways. Therefore, roles fulfilled by mature astrocytes, including ion and transmitter homeostasis, are underdeveloped in the young brain.Similarly, astrocytic ion signalling in response to neuronal activity, a process central to neuron-glia interaction, differs between the neonate and mature brain. This review describes the unique functional properties of astrocytes in the first weeks after birth and compares them to later stages of development. We conclude that with an immature neuronal network and wider extracellular space, astrocytic support might not be as demanding and critical compared to the mature brain. The delayed differentiation and maturation of astrocytes in the first postnatal weeks might thus reflect a reduced need for active, energy-consuming regulation of the extracellular space and a less tight control of glial feedback onto synaptic transmission.

Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development

“…We also identified several non-neuronal populations, including proliferative progenitors ( MKI67 + , NUSAP1 + ), glia ( GFAP + , HOPX + ), and intermediate progenitors ( EOMES + , NHLH1 + ), that had approximately equal representation in both day 93 and day 140 COs. The role of glia and progenitor populations in neurogenesis, neuronal maturation, and neural network activity has been extensively characterized in the developing human brain ( Felix et al., 2020 ; Wilton et al., 2019 ). Their stable presence in early- and late-stage COs is likely a reflection of their similar functions in developing COs.

Figure 3 scRNA-seq Reveals Dynamic Cell Type Diversity Throughout the Developmental Trajectory of COs (A) Uniform-manifold approximation map (UMAP) of single-cell RNA-sequencing data from two COs with 8,578 cells total analyzed in one independent experiment.

…”

Altered Gap Junction Network Topography in Mouse Models for Human Hereditary Deafness

“…LSO astrocytes in the two KO models exhibited similar basic membrane properties as reported earlier for the WT, namely a very negative membrane potential and a low membrane resistance [ 1 , 37 ]. Thus, expression of Kir and K 2 P channels, which set both membrane potential and membrane resistance [ 45 ], is independent from spontaneous cochlea-driven neuronal activity. However, LSO astrocytes in both KO models exhibited more often a non-linear I / V relationship ( Figure 2 ), which is indicative of partially impaired development, as they stayed in an earlier developmental state (cf.…”

Approaches to Study Gap Junctional Coupling

“…A hallmark of classical astrocytes is their large K + conductance ( Stephan et al, 2012 ), which results in a highly negative membrane potential ( Zhou et al, 2006 ; Kafitz et al, 2008 ). Further, astrocyte properties are less constant as the expression of many astrocyte-typical proteins is regulated during early postnatal development ( Felix et al, 2020b ). For example, the expression of inwardly rectifying k + channels (Kir 4.1 ) and two-pore domain K + channels (K 2P ) increases ( Seifert et al, 2009 ; Nwaobi et al, 2014 ; Lunde et al, 2015 ; Moroni et al, 2015 ; Olsen et al, 2015 ) causing a strong decrease in membrane resistance ( R M ; Zhou et al, 2006 ; Kafitz et al, 2008 ; Stephan et al, 2012 ; Zhong et al, 2016 ).…”