Animal behavior is driven by interconnected circuits of nerve cells in the brain and the spinal cord. Although diversification of these networks through evolutionary history has led to the incredible range of behaviors we observe in animals today, little work has been done to address the fundamental question: How do neural circuits evolve? One way in which neural circuits may change is through the addition of new nerve cells to the brain and their subsequent incorporation into functional networks. This research uses the startle neural circuit of fish to explore the effects of adding new nerve cells to circuits. The startle circuit is advantageous to use as a case study for examining mechanisms for changing circuits because it includes relatively few and easily identified nerve cells and controls a discrete and well-described behavior. New startle neurons will be genetically introduced into the hindbrain. Physiological recordings and laser ablation techniques will be used to examine the role specific cells play in the animal?s behavior. It is hypothesized that while new nerve cells make some connections into preexisting circuits other connections will be restricted and that redundancy of function within circuits may act to mask aberrant nerve cell activity, preventing it from disrupting behaviors. By investigating how new nerve cells integrate into simple neural circuits in the brain, this research will provide a case study for understanding principles by which circuits may be modified through evolution and insight into the flexibility for and constraints on such changes. The broader impact of this proposal includes outreach to middle school girls in disadvantaged areas of the south side of Chicago through activities in schools and in the research laboratory. In addition, this proposed research will involve undergraduates and graduate students, providing opportunities for training in a diverse array of scientific approaches and methodologies.
With this project we examine how the brain is organized and drives behavior. We use the zebrafish as a model system because their genetics are well known, their brain organization shares a number of underlying organizational features with other vertebrates and, as larvae, they are transparent making the brain and spinal cord optically accessible. The behavioral system we study is the startle response, the rapid, high acceleration response to a threatening stimulus. Across the large majority of animal species, the startle is elicited by a simple network of large-sized nerve cells. Unlike the neural underpinnings of many other behaviors, we an identify startle circuit neurons, in some cases, down to the level of the individual neuron. This accessibility of the circuit and background understanding of its components, provide a foundation for experimental and comparative approaches to neural circuit structure and function. We have found that when we use molecular approaches to introduce startle nerve cells into the brain in different locations from where they are normally found (ectopic neurons), that the brain has significant abilities to integrate those cells into functioning networks. However, these abilities to connect are not uniform and seems to depend on the location of the connecting neurons and their normal projection patterns. Another way to examine how brain and neural circuit structure relate to behavior is to compare brain and behavior across a range of species. Through a broad comparison across vertebrate animals we found that there are several discrete changes in the brain circuit that controls startles. One of the big changes occurs in teleost fishes, the massive radiation of bony fishes that dominates our saltwater and freshwater environments, leading to the question of whether increase in startle performance (and escape from predators), was a factor in the success of this group. Through the course of this study we also had to address a fundamental underlying question about the functions of the startle circuit. Specifically, we examined whether there were two distinct subtypes of startle in larval zebrafish and other species. We found that an overlapping neural circuit can generate two distinct behaviors, providing new insight into the system. This finding also changes how we interpret physiological and behavioral data for this model of nervous system function. Along with the research components of this project, it has included education and outreach components. A number of undergraduate and graduate students have been trained on this project and have gone on to pursue careers in scientific research and medicine. Outreach to local schools was performed as part of a program, Sisters-4-Science run through the organization Project Exploration, that brings women scientists to local schools to work with middle school girls. In addition to leading activities such as brain dissections and reinforcing the scientific method, we share our own research and lives as scientists.
