Abstract

Taking advantage of two Otp-specific reporter lines of transgenic mice (Otp-eGFP and Otp-Cre; Rpl22-HA), we identify and describe different Otp cell populations across various pallial regions, including the pallial amygdala, the piriform cortex, the mesocortex, the neocortex, and the hippocampal complex. Some of these populations can be followed throughout development, suggesting migration from external sources (for example, those of the pallial amygdala and at least some of the cingulate cortex). Other cells become visible during postnatal development (some of those in the neocortex and hippocampal formation) or in adulthood (those of the parahippocampal lobe), and seem to be produced locally. We discuss the possible role of Otp in these different populations during different moments of ontogenesis. We also analyze the connectivity patterns of some of these cells and discuss their functional implications. For example, our data suggest that Otp cells of the pallial amygdala might be engaged in networks with other Otp cells of the medial amygdala with the same embryonic origin, and may regulate specific aspects of social behavior. Regarding Otp cells in the parahippocampal lobe, they seem to be projection neurons and may regulate hippocampal function during spatial navigation and memory formation. The two reporter transgenic mice employed here provide very powerful tools for high precision studies on these different Otp cells of the pallium, but careful attention should be paid to the age and to differences between lines.

Highlights

  • Neuron classification across cerebral cortex and other parts of the brain is undergoing a revolution thanks to the incorporation of powerful data from single cell transcriptomics, proteomics, genomics and epigenomics, which allow high-resolution analysis of cells across different areas, and explain how they originate and function in relation to landscapes that dynamically change throughoutPallial Otp Cells ontogenesis or in disease (Trapnell, 2015; Tasic et al, 2018; Yuste et al, 2020; Armand et al, 2021; Zhang et al, 2021)

  • Using two Otp-specific reporter lines of transgenic mice, our results provide new evidence for the presence of different populations of Otp cells in various areas of the pallium, including the pallial amygdala, the neocortex, the piriform cortex, the claustrum and endopiriform nuclei, the hippocampal formation and the parahippocampal lobe

  • Otp cells of the pallial amygdala: A previous experimental study showed that, during embryonic development, Otp cells of the preoptic area, medial bed nucleus of the stria terminalis (BSTM) and medial amygdala originate in the supraopto-paraventricular domain (SPV) hypothalamic domain (García-Moreno et al, 2010), and we showed that the vast majority of these cells originate in the telencephalon-opto-hypothalamic domain (TOH) domain, at the frontier between telencephalon and hypothalamus, and coexpress Otp and Foxg1 (Morales et al, 2021)

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Summary

INTRODUCTION

Neuron classification across cerebral cortex and other parts of the brain is undergoing a revolution thanks to the incorporation of powerful data from single cell transcriptomics, proteomics, genomics and epigenomics, which allow high-resolution analysis of cells across different areas, and explain how they originate and function in relation to landscapes that dynamically change throughout. This approach is helping to better understand the evolution of different cell types by discerning between conservation, divergence, and convergence processes (Tosches et al, 2018; Yuste et al, 2020; Colquitt et al, 2021) Some of these studies have provided insightful conclusions when using transcription factors vs activity-dependent proteins. Cell-type specific genetic tools using reporter transgenic animals are very powerful to gain access to individual neuron populations for high precision studies on their distribution, morphology, molecular features, connectivity, and function (Daigle et al, 2018) Studies using this approach are still in their infancy, but they are providing enormous amounts of data that are helping to identify new cell types. The latter transgenic mouse was used for confirmatory purposes on the presence of Otp cells across different areas of the pallium

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