UCLA

Vertebrate models of learning and memory are hampered by massively complex neural circuits. Further, the engrams of memory in many vertebrate systems are highly distributed, increasing the difficulty of their identification. Invertebrate models, which possess much simpler nervous systems, have been used to relate neuronal changes to behavior changes. However, these invertebrate models are phylogenetically distant, and are physiologically and functionally different from mammalian systems. An ideal model to investigate plasticity or memory in vertebrates would entail a simple neural circuit. One such model, the zebrafish, or danio rerio, offers a variety of advantages in this regard. In addition to its rapid development, high fecundity, and ease of genetic manipulation, it is transparent at the larval stage, making future experimentation in calcium imaging readily available. Additionally, the zebrafish contains a simple neural circuit that mediates a simple behavior. This behavior is the c-start escape response (figure 1), which is dependent on large, bilaterally paired Mauthner cells in a well-understood neural circuit. Because of this, the zebrafish model presents an ideal model in the elusive understanding of the cellular mechanism of learning and memory.

The purpose of my thesis is to develop the zebrafish c-startle escape response as a new model of learning and memory to facilitate assignment of neural function and structure to behavioral memory. To achieve this goal, I have pursued numerous avenues, the first being to define many of the basic response properties that influence the escape response, in order to enable efficient and rational design of learning assays. Through experimentation, I've determined some of the factors that influence the escape response, such as volume of water, the zebrafish circadian rhythm, and even certain acoustic properties of the stimulus itself (pulse length, frequency, decibel). Other experiments to discover and describe other factors that may affect the escape response, such as boldness, will also be discussed.

A secondary goal of my thesis is to discover and reveal new types of memories in the escape response of the zebrafish, such as sensitization and classical conditioning. Using an alarm pheromone, H3NO, we've managed to sensitize the c-start response, and have also elucidated the phototaxic preferences of the zebrafish. These results will certainly lead into studies on classical conditioning of the escape response, such as association of a neutral stimulus (amino acid water) with the alarm pheromone.

Ultimately, these projects should elucidate neural function and plasticity at the M-cell synapse and set the stage for more in depth neurophysiological investigation.