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Exploring the triad of behaviour, genes and neuronal networks: Heritability of
instrumental conditioning and the Arc/Arg3.1 gene in hippocampal coding
Malkki, H.A.I.
Publication date 2013
Link to publication
Citation for published version (APA):
Malkki, H. A. I. (2013). Exploring the triad of behaviour, genes and neuronal networks: Heritability of instrumental conditioning and the Arc/Arg3.1 gene in hippocampal coding.
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For animals, the ability to navigate an environment and to form lasting, yet flexible memories of preferred and avoided locations, is essential for foraging. Similarly, acquiring and
consolidating events such as actions and outcomes, as well as to flexibly alter such associations is one of the core skills for survival.
The importance of the mouse as an animal model in neuroscientific research has increased sharply in the past decade due to the vast amount of available genetic and molecular tools. However, mouse models of flexible learning, particularly in forms other than fear learning, have been scarce. Similarly, most previous animal studies attempting to elucidate the neuronal processing underlying memory consolidation processes used the rat as an animal model.
The scope of this thesis is twofold: First, we studied acquisition and extinction of
instrumental conditioning by quantitative genetics, which allows identifying the heritable background of behavioural traits as well as suggesting chromosomal areas and even genes attributed to them. We aimed to develop and validate a flexible appetitive learning protocol that would require a relatively low number of training sessions and allow high-throughput screening of mouse lines of interest. Using this training protocol, we characterized the performance of common inbred mouse strains in a series of appetitively motivated learning tasks. We also phenotyped a set of recombinant-inbred mouse lines using this task to assess the heritability and dissociability of different stages of operant/instrumental learning and subsequent extinction, and to distinguish chromosomal areas that regulate these stages. Furthermore, mouse lines with specific deficits in one or more of these stages have the potential to become mouse models in studying cognitive impairments and perseverative disorders.
The second part of the thesis focuses on hippocampus-dependent spatial learning. Like operant behaviour, plasticity and spatial coding in the hippocampus are under genetic control. In order to dissect the neuronal processes that underlie acquisition and consolidation of spatial learning, we used a mouse model that lacks function of the Arc/Arg3.1 gene that has, on the one hand, been shown to play an important role in synaptic plasticity and that, on the other hand, has been associated with deficits in memory consolidation and in spatial learning. To bridge the gap between findings that describe the effect of loss of Arc/Arg3.1 function at the level of synaptic plasticity with behavioural findings, we recorded hippocampal neuronal spiking activity and local field potentials in behaving mice which were exploring different environments.
