Cortical interlaminar astrocytes across the therian mammal radiation

Abstract

Interlaminar astrocytes (ILA) in the cerebral cortex possess a soma in layer I and extend an interlaminar process that runs perpendicular to the pia into deeper cortical layers. We examined cerebral cortex from 46 species that encompassed most orders of therian mammalians, including 22 primate species. We described two distinct cell types with interlaminar processes that have been referred to as ILA, that we termed pial ILA and supial ILA. ILA subtypes differ in somatic morphology, position in layer I, and presence across species. We further described rudimentary ILA that have short GFAP+ processes that do not exit layer I, and “typical” ILA with longer GFAP+ processes that exit layer I. Pial ILA were present in all mammalian species analyzed, with typical ILA observed in Primates, Scandentia, Chiroptera, Carnivora, Artiodactyla, Hyracoidea, and Proboscidea. Subpial ILA were absent in Marsupialia, and typical subpial ILA were only found in Primate. We focused on the properties of pial ILA by investigating the molecular properties of pial ILA and confirming their astrocytic nature. We found that while the density of pial ILA somata only varied slightly, the complexity of ILA processes varied greatly across species. Primates, specifically bonobo, chimpanzee, orangutan, and human, exhibited pial ILA with the highest complexity. We showed that interlaminar processes contact neurons, pia, and capillaries, suggesting a potential role for ILA in the blood-brain barrier and facilitating communication among cortical neurons, astrocytes, capillaries, meninges, and cerebrospinal fluid.

Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains

“…The regional specificity of the astrocytic human-specific expression differences matches reports of molecular and functional heterogeneity of astrocytes in adult brain regions [Haim and Rowitch, 2017]. In turn, excess of astrocytic human-specific expression differences matches histological differences reported between humans and the other primate species for interlaminar astrocytes, polarized astrocytes, and varicose projection astrocytes [Oberheim et al, 2009;Falcone et al, 2018]. Similarly, oligodendrocyte progenitor cells showing rapid expression evolution in human caudate nucleus were reported to dysfunction in the caudate nucleus of schizophrenia patients [Georgieva et al, 2006;Uranova et al, 2007;Cassoli et al, 2015;Mauney et al, 2015], a disorder suggested to affect aspects of cognition particular to humans [Konopka and Geschwind, 2010;Dean, 2009].…”

Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

“…Layer I astrocytes exhibited a unique vulnerability to AD-like pathology in chimpanzees. Layer I of the primate cortex contains interlaminar astrocytes, a distinctive class of astrocytes which show greater complexity in primates compared to other mammals (Colombo, 1996;Colombo, 2001;Colombo, Gayol, Yañez, & Marco, 1997;Colombo, Hartig, Lipina, & Bons, 1998;Colombo & Reisin, 2004;Falcone et al, 2018;Oberheim et al, 2009). The somata of these interlaminar astrocytes in layer I possess long processes that extend deep into the cortical layers, terminating in layers III and IV.…”

“…Astrocyte morphology and function appears to have evolved in humans and in tandem with other cortical microstructural features. These modifications may work to render humans more susceptible to neuropathologies such as AD (Colombo, Quinn, & Puissant, ; Colombo, Yáñez, Puissant, & Lipina, ; Falcone et al, ; Magistretti, ; Oberheim et al, ; Oberheim, Wang, Goldman, & Nedergaard, ). Studies in aged great apes have reported the presence of senile plaques and tau pathology (Edler et al, ; Gearing, Rebeck, Hyman, Tigges, & Mirra, ; Gearing, Tigges, Mori, & Mirra, ; Gearing, Tigges, Mori, & Mirra, ; Kimura et al, ; Perez et al, ; Rosen et al, 2008; Selkoe, Bell, Podlisny, Price, & Cork, ).…”

Modeling human‐specific interlaminar astrocytes in the mouse cerebral cortex

“…It is not known whether the organized structure of neuronal columns serves as the prerequisite for the development of interlaminar processes. Reciprocally, interlaminar astrocytes have been shown to come in close contact with MAP2 positive dendrites (Falcone et al, 2019) and here we show interaction with VGLUT1 positive presynaptic terminals, but whether interlaminar astrocyte activity modulates neuronal activity is yet to be investigated.…”

“…Two-site injection resulted in the widespread distribution of RFP-expressing hiPSC-astrocytes in the frontal cortex (Figure 2b,c). In the un-injected hemisphere of the same chimeric mice, GFAP immunostaining revealed only the recently described mouse rudimentary interlaminar astrocytes (Falcone et al, 2019), with very short processes that do not exit layer I, as well as the typical protoplasmic astrocytes in other cortical layers (Figure 3d). While at what are likely to be sites of engraftment of hiPSC-astrocytes, thick bands of cell bodies are found in the superficial cortex, further away, cells are mainly confined to layer 1 (Figure 2c and Figure 3).…”