Periodic Reporting for period 3 - BehavIndividuality (Uncovering the basis of behavioral individuality across developmental time-scales)
Reporting period: 2022-12-01 to 2024-05-31
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.
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. We already found tens of candidate genes that are expressed within the nervous system that show association to differences in behavior among individuals and performed validation of their involvement. 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 different methods from various field for understanding fundamental processes that organize behavioral variation among individuals.
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. We already found tens of candidate genes that are expressed within the nervous system that show association to differences in behavior among individuals and performed validation of their involvement. 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 different methods from various field for understanding fundamental processes that organize behavioral variation among individuals.
The discoveries that we made so far within the project are significantly beyond the state of the art. For example, showing for the first time in any organism that there are multiple individuality types within isogenic populations across developmental timescales. We also demonstrated the dynamic representation of these types within populations, which depended on early-life experiences. We also identified for the first-time variable genes within isogenic populations that are associated with individuality patterns. We expect by the end of the project, to both extend our discoveries to other behavioral paradigms, as well as identify exact underlying molecular and neuronal states that generate inter-individual behavioral diversity.