Periodic Reporting for period 4 - BehavIndividuality (Uncovering the basis of behavioral individuality across developmental time-scales)
Período documentado: 2024-06-01 hasta 2025-11-30
Long-term behavioral patterns across development are highly dynamic across and within developmental stages and temporally synchronized with the individual’s developmental clock. However, while long-term behavior may be shared by many individuals, reflected by stereotypic behavioral patterns, individuals within the same population may also show unique patterns of behavior that distinguish them from each other. This inter-individual variation in behavior exists even when animals are experiencing the same environment and have the same genotype. This phenomenon, which was characterized across multiple species, from invertebrates to humans, implies that there are additional non-genetic mechanisms that generate behavioral variation among individuals. Studying these novel sources of behavioral variation is crucial for the basic understanding of why individuals behave differently and may also shed light on sources of the emergence of mental disorders only in some individuals within the population. The general objectives of our project are: (1) understanding the underlying molecular differences across individuals, within the nervous system, that generate behavioral variation (2) exploring how these changes affect the nervous system’s function to affect behavioral diversity and (3) studying how different environments (like stress) affect variation in behavioral responses within the population. The results from these studies will uncover fundamental and conserved biological processes that generate behavioral diversity across development.
Overall, the action has successfully achieved its core scientific objectives by establishing a mechanistic and conceptual framework for understanding how behavioral individuality is generated, maintained, and reorganized across development. By combining large-scale longitudinal behavioral analysis with neuronal and environmental perturbations, as well as single-individual molecular profiling, the project has revealed how neuromodulatory processes interacts with developmental dynamics, to shape stable yet flexible individual differences in behavior. The tools, datasets, and conceptual advances developed through this action provide a lasting foundation for additional mechanistic studies and broadly enable the investigation of individuality across neural, developmental, and behavioral systems.
Overall, the action has successfully achieved its core scientific objectives by establishing a mechanistic and conceptual framework for understanding how behavioral individuality is generated, maintained, and reorganized across development. By combining large-scale longitudinal behavioral analysis with neuronal and environmental perturbations, as well as single-individual molecular profiling, the project has revealed how neuromodulatory processes interacts with developmental dynamics, to shape stable yet flexible individual differences in behavior. The tools, datasets, and conceptual advances developed through this action provide a lasting foundation for additional mechanistic studies and broadly enable the investigation of individuality across neural, developmental, and behavioral systems.
During the first period of the ERC project, our group made significant progress and achieved many of our scientific goals towards understanding the internal neuronal and molecular mechanisms and the external environments that shape behavioral individuality across development.
First, we discovered that starvation early in life generates distinct behavioral effects across different life stages that are temporally mediated by the segregated function of different neuromodulatory pathways. These complex long-term effects of stress are manifested by buffering if behavioral alterations during mid-development and by exposing strong effects at early and late stages. In addition, a novel unsupervised analysis of temporal patterns of individual biases across development uncovered, for the first time, multiple individuality types that coexist within isogenic populations and further identified specific neuromodulatory effects on their composition following early starvation.
Second, we studied the underlying mechanisms of individuality by identifying stochastic differences in gene-expression states that generate stable behavioral individuality within population. We developed a protocol for measuring both behavioural and gene-regulatory states at the individual level, across hundreds of individuals. Third, we focus on identifying neuronal circuits that are involved in generating inter-individual variation in the context decision making across development. We have already developed a unique experimental paradigm and custom-made computational methods for analyzing variation in decision making time across development and under various environmental conditions. Altogether, we utilized diverse methods from multiple fields to investigate the fundamental processes that organize behavioral variation among individuals. In summary, this action delivered a comprehensive and mechanistic understanding of behavioral individuality across development, including how developmental history shapes individual differences. Specifically, we demonstrated that early-life stress reorganizes behavioral individuality in a stage-specific manner, revealing temporally segregated effects controlled by distinct neuromodulatory systems (Ali Nasser et al. 2023). The project further established structured developmental behavioral spaces that capture both conserved and individual-specific dimensions of behavior (Cell Reports; Harel et al. 2024) and introduced an experimental framework enabling the direct linkage of behavioral phenotypes and gene-expression states within the same individual animal (Ganem et al. 2025). These empirical advances are integrated into a broader conceptual framework defining emerging principles of behavioral individuality across timescales and biological levels (Current Opinion in Neurobiology; Flavell, Oren-Suissa, Stern 2025). Together, these results define new principles governing the generation, and time-organization of individual behavioral differences and provide a foundation for future studies of variability in neural and behavioral systems.
First, we discovered that starvation early in life generates distinct behavioral effects across different life stages that are temporally mediated by the segregated function of different neuromodulatory pathways. These complex long-term effects of stress are manifested by buffering if behavioral alterations during mid-development and by exposing strong effects at early and late stages. In addition, a novel unsupervised analysis of temporal patterns of individual biases across development uncovered, for the first time, multiple individuality types that coexist within isogenic populations and further identified specific neuromodulatory effects on their composition following early starvation.
Second, we studied the underlying mechanisms of individuality by identifying stochastic differences in gene-expression states that generate stable behavioral individuality within population. We developed a protocol for measuring both behavioural and gene-regulatory states at the individual level, across hundreds of individuals. Third, we focus on identifying neuronal circuits that are involved in generating inter-individual variation in the context decision making across development. We have already developed a unique experimental paradigm and custom-made computational methods for analyzing variation in decision making time across development and under various environmental conditions. Altogether, we utilized diverse methods from multiple fields to investigate the fundamental processes that organize behavioral variation among individuals. In summary, this action delivered a comprehensive and mechanistic understanding of behavioral individuality across development, including how developmental history shapes individual differences. Specifically, we demonstrated that early-life stress reorganizes behavioral individuality in a stage-specific manner, revealing temporally segregated effects controlled by distinct neuromodulatory systems (Ali Nasser et al. 2023). The project further established structured developmental behavioral spaces that capture both conserved and individual-specific dimensions of behavior (Cell Reports; Harel et al. 2024) and introduced an experimental framework enabling the direct linkage of behavioral phenotypes and gene-expression states within the same individual animal (Ganem et al. 2025). These empirical advances are integrated into a broader conceptual framework defining emerging principles of behavioral individuality across timescales and biological levels (Current Opinion in Neurobiology; Flavell, Oren-Suissa, Stern 2025). Together, these results define new principles governing the generation, and time-organization of individual behavioral differences and provide a foundation for future studies of variability in neural and behavioral systems.
The discoveries made within this project significantly advance the state of the art in the study of behavioral individuality. Notably, we demonstrated for the first time in any organism the existence of multiple, structured individuality types within isogenic populations across developmental timescales. Using large-scale longitudinal behavioral data and unsupervised analytical approaches, we identified distinct individuality dimensions that emerge directly from behavior, revealing a structured organization of individual differences beyond population averages. We further showed that the representation of these individuality types and dimensions within populations is dynamic and is shaped by early-life experiences, uncovering a developmental reorganization of behavioral variation. In addition, we identified variable gene-expression states within isogenic populations that are associated with stable individual behavioral patterns, providing direct molecular correlates of individuality. Together, these results establish a mechanistic framework linking developmental history, neuromodulatory and molecular variability, and long-term behavioral diversity, moving the field beyond descriptive population-level analyses toward single-individual understanding of behavioral variation.