Associative learning and memory in zebrafish

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Learning and memory are complex biological processes whose mechanisms are still poorly understood. In 2005, we proposed to use a simple vertebrate, the zebrafish, to start studying learning and memory. We argued that the simplicity of this vertebrate, and the fact that it represents an evolutionarily ancient biology, will allow us to discover the most fundamental, that is, core features and mechanisms of learning & memory. Because of the simplicity of this species, we also argued that with the zebrafish such discoveries may be made in a more efficient manner than what would be possible with other laboratory organisms. We completed an NSERC grant in which we characterized features of zebrafish (for example, how they move, what stimuli they respond to and what motivates them) that were crucial for running learning tasks and for interpreting the results of these tests. In the second NSERC grant cycle (starting in 2011) we developed numerous learning tasks for zebrafish, and demonstrated that despite the simplicity of this species, zebrafish are capable of learning complex spatial tasks. This type of learning is what supports episodic memory in humans, a form of memory that allows us to remember who we are and what happened to us throughout our life. In the current application, we now propose to extend our work to the characterization of memory in zebrafish. We will study short-, medium- and long-term memory using simple (non-spatial), complex associative relational (spatial) and procedural (skill-related) memory tasks. We will develop computerized stimulus delivery and behavioural response quantification methods that will allow us to run the memory tests in an automated manner without human interference. We will use drugs to manipulate memory phases and forms. We will also test mutant zebrafish in which known genes are disrupted, as a proof of concept study for future high throughput screening for novel mutations (and genes) involved in learning & memory. Numerous sophisticated genetic methods have been developed for the zebrafish, but very little is known about its learning & memory characteristics. Thus, mechanistic analysis of these complex processes has not been possible. The goal of our proposal is to fill this gap, and make the behavioral pillar of the behavior genetics bridge as strong as its genetics pillar is. Ultimately, our studies with zebrafish will answer many questions about how memory is formed, stored and recalled, questions fundamentally important to our every day life.