Carlos D. Aizenman - US grants

The scientific goal of this project is to understand the mechanisms by which the external environment shapes the way the nervous system is wired. The brains of developing organisms face an immense challenge since they must allow the organisms to function within their environment even while the nervous system is not yet fully developed. It is not fully known how the brain achieves the balance between early function and the need to remain flexible. One strategy employed by the brain to achieve this is through a process called neural plasticity, which allows brain circuits to adapt to patterns of sensory input received from the external environment. This project uses the developing visual system of frog tadpoles as a model for early brain development. Experiments will study the correlation between the developmental emergence of visually-guided swimming behavior to the properties of tiny electrical signals generated in the tadpole brain in response to visual stimuli. This will allow investigators to first map neural circuits involved in processing visual stimuli and then to understand the role of the visual environment in building this circuitry through neural plasticity. For example, if visual input is required for proper wiring of visual circuits, then tadpoles raised in a dark environment or under conditions in which communication between the eye and brain is disrupted, are expected to develop abnormally. This study will also focus on mechanisms by which the brain can adapt to deficits in sensory input to achieve normal function. Together, these experiments will provide important insight into the mechanisms by which the brain's complex circuitry emerges during development and which allow it to adapt to a changing environment. A second goal of this project is to develop an educational program which will allow high-school students from underrepresented minority groups to engage first-hand in this research. This program will allow for two students each year to come to Brown and participate in a basic Neuroscience course and work in Dr. Aizenman's laboratory over the summer. The ultimate goal is to encourage these students to pursue a career in the life sciences by providing first-hand laboratory experience and mentoring. In addition, the program will also provide training opportunities to undergraduate and graduate students in the laboratory.

The only way to truly understand how the human brain works is to understand how it is first put together during early development. To do this, we need to first grasp, at a basic level, the fundamental principles by which developing brain circuits are initially formed and how early experience can shape these connections. This project addresses these questions by studying the development of the visual system of tadpoles from the African clawed frog, Xenopus laevis. This relatively simple brain circuit allows investigators to ask highly tractable questions about early brain development and answer them by designing experiments that investigate development at the level of single brain cells to the more complex behavior of brain circuits, and ultimately, to complex behaviors. Thus, these studies will provide an understanding of the mechanisms underlying visually guided behavior from initial perception in the eye all the way to behavioral output. An in-depth, integrated, view of this developing brain circuit can be used to derive fundamental principles of brain development. Remarkably, these principles have been shown to be applicable to all vertebrates including humans. This proposal continues a program established by the investigator to run a Neuroscience Summer Fellowship at Brown University for underrepresented minority high-school students, with the goal of increasing the participation of these students in careers related to Science, Technology, Engineering, and Mathematics (STEM).

Specifically, this proposal seeks to understand the mechanisms by which neural circuits in the Xenopus tadpole optic tectum allow the organism to process incoming sensory information and transform it into meaningful motor output. This sensory-motor transformation is essential for the organism to interact with its environment. Data from many levels of analysis will be integrated, including recording from retinal ganglion cells in the eye, recording the balance of excitation and inhibition and spike output of the tectum in vivo, recording network activity of multiple tectal cells in vivo using calcium imaging, quantifying visually guided behavior with a high speed camera, and using dynamic clamp to probe the integrative properties of tectal neurons in response to behaviorally relevant stimuli. Together these data will give us an unprecedented understanding of the steps and circuitry involved.

Project Summary/Abstract Assessment of current programs designed to increase diversity in STEM disciplines at Brown University has revealed the need to specifically address the critical transition from undergraduate into doctoral training programs. The goal of Brown PREP is to diversify and enrich the biomedical research endeavor by increasing the number of students enrolled in and completing doctoral training programs. Informed by best practices and lessons learned from an institutional pilot PREP program, we describe an innovative program characterized by a comprehensive and customizable set of interventions to support and advance underrepresented students' academic and career development. Each year, our program will recruit and support eight research-oriented baccalaureate graduates from underrepresented backgrounds and provide them with interdisciplinary research experiences, individualized academic planning, professional development, and skill-building activities to increase their competitiveness and readiness for high-caliber doctoral programs. Participating departments for Brown's proposed PREP reside in the Life and Medical Sciences Division and include biology, neuroscience, psychology, public health and cognitive, linguistic and psychological sciences. In addition to intensive interdisciplinary research experiences and knowledge development, multiple mentorship and community building opportunities permeate the activities of the Brown PREP. Creating a community of scholars that will help students successfully navigate program requirements is viewed as essential to helping students reach their full potential in a short period of time. The use of Individual Development Plans (IDP) will ensure that the Brown PREP research, educational and professional development activities are specifically tailored to address each student's academic and career goals. As important, the Brown PREP will provide opportunities for faculty to engage in conversations about the importance of developing a diverse workforce in the biomedical and behavioral sciences. We have developed a comprehensive evaluation plan to assess outcomes and progress toward meeting the overall goal and aims of this project and monitor quality assurance across the proposed interventions. As designed, the Brown PREP will increase the production of underrepresented students who obtain a doctoral degree in the biomedical sciences; institutionalize best practices on training and mentoring diverse scholars that can be shared among the Brown community and beyond; and diversify the biomedical research workforce.