Periodic Reporting for period 1 - TERRITORY (The neural basis of dynamic territorial aggression and fear)
Periodo di rendicontazione: 2023-05-01 al 2025-10-31
The urge to defend one’s territory is an evolutionarily conserved instinct aimed at securing optimal access to food, mates, and shelter. Conflict arises when territories become unstable due to seasonal changes in resource availability, or when population density increases. Under such conditions, individuals must carefully balance social aggression and avoidance to maximize their control of territorial resources while avoiding subordination at the hands of their neighbors. What is the neural basis of such dynamic territorial behaviors? We have found that an evolutionarily conserved medial hypothalamic brain structure serves as a switch between social aggression and avoidance. In this proposal we ask where and how is territory encoded in the brain and how could it control this hypothalamic switch? A clue emerges from recent work in which we discovered that neural activity in this structure encodes a map of social space much like the mammalian hippocampus encodes a map of navigational space. However, unlike hippocampal place cells that arise spontaneously as animals explore, hypothalamic territory cells require social experience to form. We will develop a semi-natural laboratory testing environment where we can monitor the dynamic acquisition of territories in mice over time and apply in vivo neural recording, activity perturbation, and computational modelling to extract precise synaptic integration and plasticity mechanisms that underlie territory-based decision-making in the mammalian brain. Uncovering the neural basis of territorial behaviors is an essential step toward a biological understanding of human aggression and fear and could provide insight into interventions for maladaptive responses to threats to personal space, resources, and beliefs.
During the initial funding period we have completed our initial experiments establishing and validating the large semi-natural behavioral testing apparatus for eliciting territorial behaviors in pairs of male mice. We also established all the methods needed for the recording of neuronal ensemble activity in vHIP and VMHvl in this apparatus, including the necessary automated behavioral quantification methods. Finally, we have established several novel tools that will be critical in the next steps to understand cellular-level function and plasticity in these circuits. The following list highlights our major accomplishments during this funding period:
• Recruit and retain the necessary personnel to launch the ERC project
• Established a semi-natural territorial behavioral apparatus and testing protocols and allow us to monitory the evolution of robust territorial behaviors in laboratory mice (Battivelli et al. Sci Rep 2024; Battivelli et al. Nat Rev Neurosci 2024)
• Successfully establish a number of technologies necessary for in vivo and in vitro monitoring of neural plasticity and efficient long-term neural manipulation and inhibition
• Recruit and retain the necessary personnel to launch the ERC project
• Established a semi-natural territorial behavioral apparatus and testing protocols and allow us to monitory the evolution of robust territorial behaviors in laboratory mice (Battivelli et al. Sci Rep 2024; Battivelli et al. Nat Rev Neurosci 2024)
• Successfully establish a number of technologies necessary for in vivo and in vitro monitoring of neural plasticity and efficient long-term neural manipulation and inhibition
The project aims to understand the neural circuit basis of how the mammalian brain modulates social dominance behavior based on territorial context. If successful, the outcome of the project could have significant impact both on further basic neruoscience research as well as in translational research aimed at addressing the pharmacological modulation of human dominance-related states and related mental suffering. Its predicted impat on basic neruoscience research centers on its aim to develop methods to measure territorial behavior in laboratory animals that has so far only been described in wild species. Such an advance would open up avenues to use technologies like brain recording and manipulation only available in the laboratory to understand these beahviors. At the same time basic resaerch wodul be advanced by its demonstration that spatial control regions in the brain (e.g. hippocampus) also control innate social behavior centers in the instinctive parts of our brains (e.g. hypothelamus). This advance has great conceptual value and sets precedent for a new manner of considering how mammalian brains regulate social behaviors. Finally, the understanding generated by the proposal could be used to identify neural circuit targets to which drugs could be designed for the relief of pathological (i.e. associated with suffering) social behaviors (e.g. social anxiety and aggression, shame and embarrassment).