Tomchik Lab Research
How does learning influence information flow in the brain?
How do genetic disorders affect neuronal function?
Our research focuses on dissecting the mechanisms of learning and memory in normal conditions and in models of genetic disorders (e.g., neurofibromatosis type 1 [NF1]). Genetic disorders such as NF1 affect learning and memory, as well as a range of other cognitive and behavioral processes, increasing the risk of developing attention-deficit/hyperactivity disorder, autism spectrum disorder, and others. Therefore, we seek to understand both how learning and memory works in normal conditions, as well as how genetic disorders affect neuronal function broadly. This research involves technical approaches ranging from genetics & biochemistry to in vivo imaging with genetically-encoded fluorescent reporters and circuit manipulation with thermo/optogenetics. These experiments involve the mechanistically powerful genetic model organism Drosophila melanogaster and human induced pluripotent stem cells.
Learning and Memory
Humans and animals are endowed with great capacity to adjust our behaviors, allowing us to respond appropriately to different situations. This capacity for learning is one of the most important and fundamental functions of our brain, which is why memory loss is so catastrophic to individuals, their families, and the health care system. Our lab endeavors to understand how memory works, and how it fails in diseases that result in memory loss. To reveal how the 86 billion neurons in the human brain support learning and memory, we must break the problem down into more tractable questions using "simpler" model organisms - ones that have fewer neurons in their brains to contend with. We therefore study neuronal function underlying learning in Drosophila. The powerful genetics of this model system, combined with our approaches for in vivo imaging and localized manipulation of neuronal activity, enable deep characterization of neuronal circuit function. We are focusing on how dopaminergic pathways are involved in shaping learning and memory. Specifically, we are studying the roles of candidate signaling molecules that are potentially involved in memory formation. In addition, we are looking at how major signaling cascades (cAMP/PKA, Ca2+, etc.) are activated during learning, and how activation of these pathways modulates the responses of the neurons that encode memories. Finally, we are examining how neuronal responses are altered following memory acquisition or upon salient environmental changes, with a focus on dopaminergic circuit function.
Neurofibromatosis type 1
Neurofibromatosis type 1 (NF1) is a disorder characterized by tumors and cutaneous symptoms, but also increases risk for cognitive and behavioral alterations. Approximately 60% of people with NF1 have attention problems (such as attention-deficit/hyperactivity disorder [ADHD]) and ~14% have autism spectrum disorder. Therefore, the genetic mutation that causes NF1 affects brain function. A major focus of our research is aimed at understanding how the genetic mutations underlying NF1 impact neuronal function, ultimately leading to behavioral changes. In pursuit of this overarching goal, we are studying how Nf1 mutations lead to hyperactivity, neuronal circuit dysfunction, and metabolic alterations in Drosophila. A major initial observation from these studies was that Nf1 mutations lead to hyperactivity and excessive grooming. This must result from overactivation of neuronal circuits that regulate motor behaviors, providing a platform to examine how Nf1 affects neuronal circuits. We are using this model to examine the neurodevelopmental contributions of Nf1 to neuronal function, elucidate the molecular biology of the disorder, examine novel protein interactions, probe the neuronal circuit effects of Nf1 mutations, and test the role of metabolic alterations that accompany NF1. The goal of these studies is to build the foundation of knowledge of the disorder that will be necessary to develop novel avenues for therapeutic intervention.
