- Exploring the triad of behaviour, genes and neuronal networks: Heritability of instrumental conditioning and the Arc/Arg3.1 gene in hippocampal coding
- Award date
- 4 December 2013
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
In this thesis, we set out to study the genetic background of neuronal function that enables adaptive behaviours that are essential for survival, such as understanding the relations between actions and outcomes and forming accurate representations of the environment.
In the experimental protocols we used, exploratory and cue-response behaviour were motivated by sweet rewards, mimicking real-life situations in which we form memories of environments and action-outcome series associated with rewards.
We demonstrated that operant learning and extinction consist of multiple stages that are dissociable, heritable and regulated by different chromosomal areas, characterized the performance of common laboratory mouse lines in acquisition and extinction tasks and suggested mouse models for perseverative disorders.
We dissected the role of Arc/Arg3.1 in neuronal processes that take place during active exploration of environment and subsequent sleep. We found that Arc/Arg3.1 knockout (KO) mice exhibited attenuated hippocampal oscillatory activity in the high frequency range and disrupted synchronized firing during track running.
Furthermore, we showed that Arc/Arg3.1 KO mice had decreased hippocampal sharp wave-ripple activity and that correlated firing activity during sleep was diminished. These alterations may explain why Arc/Arg3.1 mice are impaired spatial learning and lack memory consolidation.
Together, these findings paint an intriguing picture of the genetic background and neuronal processes involved in complex behaviours that are crucial for survival. In order to further understand and unravel this intricate linkage, we will need to continue to study the triad of genes, neuronal networks and behaviour from all its corners.
- Research conducted at: Universiteit van Amsterdam
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