Periodic Reporting for period 1 - OxytocINspace (Oxytocin-driven territorial mapping in the mammalian hippocampal formation)
Berichtszeitraum: 2023-06-01 bis 2024-11-30
How are the concepts of social hierarchy and territory ownership ("my space, our space, your space, no one's space") ingrained and integrated in our brains? The human migration out of Africa over 70,000 years ago was driven by sophisticated brain operations coordinating spatial navigation with inherent concepts of social hierarchy and cooperation as well as territories—areas of land that groups of animals or humans identify as "their own" and safeguard from intrusion by others. Territorial behavior, far from diminishing throughout human evolution, became even more central to human societies, after the advent of agriculture and settled living had established the groundwork for geographically defined territories ("borders"). Even today, it continues to significantly influence our perception of space categorized into private, public, or neutral zones.
But what are those neural mechanisms underlying an individuals' capacity to comprehend spatial geometry in the context of spatial ownership and social hierarchies, ultimately contributing to the perception of territoriality? Our brain possesses a fundamental system, primarily located in the hippocampus, which is abundant in spatially-selective neurons responsive to spatial metrics like distances, landmarks, and borders. So how is space organized into socially significant territories in the hippocampal system? Our international team proposes that this process is mediated by the Oxytocin system. Oxytocin, a neurohormone known for enhancing social activity in mammals, has recently been discovered to also modulate neural activity in the hippocampus. However, its potential role in territorial representation remains unexplored. In our study we make full use of our expertise in diverse areas of neuroscience, including social behavior, spatial navigation, neurophysiology, anatomy, and cell signaling, to examine the similarities and differences in brain function related to socio-territorial strategies across five mammalian species: bats, mice, rats, marmosets, and macaques. This comparative multi-species approach will allow us to identify common motifs as well as differences, while taking into account the diverse social and territorial life-styles of these species.
Our primary objective is to investigate how neurons encoding spatial geometry (such as place cells, boundary cells, and grid cells) respond to socially-dependent territorial parameters like ownership, utility, and hierarchies. Our cross-species perspective will for the first time offer insights into the neural circuitry governing both ancestral and contemporary mammalian territorial behavior. Moreover, the collaborative efforts of our teams will have significant implications for human mental health, providing a foundation for potential oxytocin-based treatments for alterations in individual territorial positioning observed in patients with autism spectrum disorders, borderline personality disorder, major depression, and other psychiatric illnesses.
But what are those neural mechanisms underlying an individuals' capacity to comprehend spatial geometry in the context of spatial ownership and social hierarchies, ultimately contributing to the perception of territoriality? Our brain possesses a fundamental system, primarily located in the hippocampus, which is abundant in spatially-selective neurons responsive to spatial metrics like distances, landmarks, and borders. So how is space organized into socially significant territories in the hippocampal system? Our international team proposes that this process is mediated by the Oxytocin system. Oxytocin, a neurohormone known for enhancing social activity in mammals, has recently been discovered to also modulate neural activity in the hippocampus. However, its potential role in territorial representation remains unexplored. In our study we make full use of our expertise in diverse areas of neuroscience, including social behavior, spatial navigation, neurophysiology, anatomy, and cell signaling, to examine the similarities and differences in brain function related to socio-territorial strategies across five mammalian species: bats, mice, rats, marmosets, and macaques. This comparative multi-species approach will allow us to identify common motifs as well as differences, while taking into account the diverse social and territorial life-styles of these species.
Our primary objective is to investigate how neurons encoding spatial geometry (such as place cells, boundary cells, and grid cells) respond to socially-dependent territorial parameters like ownership, utility, and hierarchies. Our cross-species perspective will for the first time offer insights into the neural circuitry governing both ancestral and contemporary mammalian territorial behavior. Moreover, the collaborative efforts of our teams will have significant implications for human mental health, providing a foundation for potential oxytocin-based treatments for alterations in individual territorial positioning observed in patients with autism spectrum disorders, borderline personality disorder, major depression, and other psychiatric illnesses.
So far, our OxytocINspace consortium members have worked on establishing the methods and paradigms required to advance towards the main goals. This includes neuroanatomical, electrophysiological, and behavioural paradigms
We have already confirmed that oxytocin nerve fibres indeed target the hippocampal formation, where territorial information is integrated, in all mammalian species studied by our consortium members. Furthermore, we have verified in various of these species that the hippocampal formation contains neurons expressing oxytocin receptors, meaning that oxytocin can modulate neural activity in this region.