NeuroParTI: Evolutionary Trade-off Analysis of Human and Macaque Monkey Neurochemistry

Kastaubh Patil – FZ Jülich
Nicola Palomero-Gallagher – FZ Jülich

The complexity and specialization of neurotransmitter and receptor (NTR) systems in humans have afforded us nuanced, adaptive behaviours and a unique spectrum of cognitive abilities. These NTR systems are the molecular foundation for communication between neurons, and a balanced NTR ecosystem is crucial for brain functioning and mental health. Disruptions in this balance have been implicated in a spectrum of neurological and psychiatric conditions, such as depression, anxiety, schizophrenia, and various cognitive impairments. Despite the pivotal role of NTRs in brain function, our understanding of these systems, particularly from an evolutionary standpoint, remains incomplete. Comprehending the NTR's organisational principles in the human brain, therefore, could yield valuable insights into the brain's structural and functional segregation, both in health and disease states. To bridge this knowledge gap, our project seeks to explore the organisational principles of NTR systems using innovative methodologies and newly accessible brain imaging data from both humans and macaque monkeys to identify evolutionary trade-offs. By juxtaposing and analysing NTR systems across species, we aim to uncover the evolutionary forces that have shaped the balance between NTR systems in humans. We perform systematic comparisons with established methods and cross-validate our findings with established facets of macroscopic brain organization and genetic correlates. This rigorous approach will offer novel insights into the fundamental neurochemical organisation of the human brain and neural underpinnings of a range of behaviours. This understanding might ultimately contribute to novel treatments for neurological and psychiatric disorders. Additionally, this project will generate a wealth of resources, including detailed imaging data describing macaque monkey NTR systems in 3D, novel methodological frameworks, and new software tools. These valuable assets, while being integral to our project, will also prove invaluable to the broader scientific community, thus extending the impact of our work beyond the immediate project scope.