Comparative Features of Calretinin, Calbindin and Parvalbumin Expressing Interneurons in Mouse and Monkey Primary Visual and Frontal Cortices

Abstract

Much is known about differences in pyramidal cells across cortical areas and species, but studies of interneurons have focused on comparisons within single cortical areas and/or species. Here we quantified the distribution and somato-dendritic morphology of interneurons expressing one or more of the calcium binding proteins (CaBPs) calretinin (CR), calbindin (CB) and/or parvalbumin (PV) in mouse (Mus musculus) versus rhesus monkey (Macaca mulatta) in two functionally and cytoarchitectonically distinct regions- the primary visual and frontal cortical areas. The density, laminar distribution and morphology of interneurons were assessed in serial brain sections using immunofluorescent multi-labeling, stereological counting and 3D reconstructions. There were significantly higher densities of CB+ and PV+ neurons in visual compared to frontal areas in both species. The main species difference was the significantly greater density and proportion of CR+ interneurons and lower extent of CaBP co-expression in monkey compared to mouse cortices. Cluster analyses revealed that the somato-dendritic morphology of layer 2-3 inhibitory interneurons is more dependent on CaBP expression than on species and area. Only modest effects of species were observed for CB+ and PV+ interneuron morphologies, while CR+ neurons showed no difference. By contrast to pyramidal cells which show highly distinctive area- and species-specific features, here we found more subtle differences in the distribution and features of interneurons across areas and species. These data yield insight into how nuanced differences in the population organization and properties of neurons may underlie specializations in cortical regions to confer species and area-specific functional capacities.

Laminar specificity and coverage of viral-mediated gene expression restricted to GABAergic interneurons and their parvalbumin subclass in marmoset primary visual cortex

“…Specifically, GABA+ and PV+ expression peaks in L2/3 and 4C in marmoset V1, but in L4 and 5 in mouse V1. Similar differences between mouse and primate V1 in the laminar distribution of PV cells were reported previously (Kooijmans et al, 2020;Medalla et al, 2023). Our results on the laminar distribution of PV and GABA immunoreactivity is consistent with previous qualitative and quantitative studies in macaque V1 (Hendry et al, 1989;Blumcke et al, 1990;DeFelipe et al, 1999;Disney and Aoki, 2008;Kelly et al, 2019;Kooijmans et al, 2020;Medalla et al, 2023), and with a quantitative study in marmoset V1 (Goodchild and Martin, 1998).…”

β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction

“…In monkey 2 (M2), we analyzed 136 CB cells, 211 CR cells, and 250 PV cells. CB cells are most dense in layer II-IIIa, and less frequent in other layers, while CR and PV neurons are plentiful in deep layer III, in line with previous reports of density across the cortical column ( Condé et al, 1994 ; Medalla et al, 2023 ). Statistics were carried out in Prism 9 (Graphpad Software, San Diego CA).…”

“…Free-floating sections were used to label β1-AR and the calcium-binding proteins PV, CB, and CR for confocal and electron microscopy. These label most inhibitory neurons in primate cortex and are largely non-overlapping ( Cond et al, 1994 ; Medalla et al, 2023 ; Joyce et al, 2020 ; DeFelipe, 1997 ). Sections underwent antigen retrieval in 10 mM sodium citrate (J.T.…”

“…The current study examined this hypothesis by exploring the expression of β1-AR on PV interneurons in layer III of macaque dlPFC using both multiple label immunofluorescence (MLIF) and immunoelection microscopy (immunoEM). We also examined β1-AR expression on inhibitory neurons labeled for calbindin (CB) and calretinin (CR), which together with PV label most inhibitory neurons in primate dlPFC ( Cond et al, 1994 ; Medalla et al, 2023 ). Previous research has documented β1-AR on dendritic spines of pyramidal cells in these circuits ( Datta et al, 2024 ), but had not tested whether they were also localized on inhibitory interneurons.…”