The perception of a stimulus is strongly influenced by the background surrounding it. In mammals, this figure-ground perception to identify stimuli from the environment is crucial for survival, such as detecting predators. My project aims to explore the neural mechanisms behind figure-ground perception, especially focusing on the role of vasointestinal peptide positive (VIP) and somatostatin (SOM) interneurons in the primary visual cortex (V1). To explore the mechanism, I will first develop a novel mice behavioral task that can accurately quantify figure-ground modulation. Then, I will use optogenetics to activate or silence VIP and SOM neurons to explore how these perturbations affect mices performance in the task. In doing so, I aim to uncover how VIP-SOM disinhibitory circuit contributes to figure-ground perception.
Mitochondrial dysregulation has emerged as a cause for certain forms of Parkinson’s disease. Investigations of the mechanisms linking mitochondrial function to Parkinson’s have focused on the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc-DA neurons). Norepinephrine-releasing neurons in the locus coeruleus (LC-NE neurons) rely on mitochondria for their daily activity in healthy individuals and also severely degenerate in Parkinson’s. Both SNc-DA neurons and LC-NE neurons are crucial for maintaining various aspects of wakefulness, but it is unclear whether mitochondrial dysregulation in each neuron population distinctly impacts sleep disturbances characteristic of Parkinson’s. For my project, I will address the hypothesis that mitochondrial dysregulation in LC-NE neurons versus that in SNc-DA neurons will have different effects on sleep in a mouse model, which could provide insight for targeted therapies to improve sleep in patients. Toward this goal, I will study mice using a targeted genetic approach where a key […]
Understanding the genetic basis of organ regeneration remains a central challenge in the field of developmental biology. Teeth are a classic model for organogenesis, since many homologous ectodermal organs (e.g., teeth and hair) follow similar patterns of development and regeneration. Threespine stickleback fish are a powerful model organism for studying tooth regeneration in vertebrates because they possess the ancestral dental phenotype of polyphyodonty, in which teeth are continuously replaced throughout adult life. Past research has shown that Foxc1 regulates Bmp6, a gene important for viability, growth, and tooth patterning in threespine stickleback fish, and maintaining quiescence, a period of rest, in mouse hair follicle stem cells. My project aims to study whether Foxc1a and Foxc1b are required for regulating tooth regeneration in threespine sticklebacks. I hypothesize that Foxc1a and Foxc1b play homologous roles in reestablishing quiescence in fish tooth stem cells as Foxc1 does in past studies of mouse […]
People with high level of nearsightedness will have a 5- to 10-fold chance of developing glaucoma, cataract, and sight-threatening diseases such as retinal detachment later in life. Atropine eye drop is one of the most effective therapies for nearsightedness control. I will conduct a small-scaled randomized controlled trial to understand the impact of eye color on the effectiveness of atropine eye drop. Many studies on atropine have focused on Asian populations, and few studies have compared the effect of atropine between Asians and Europeans, who tend to have much lighter iris color and might respond to the drug differently. A prior animal study has shown that the effect of atropine diminishes quicker in rabbits with lighter iris color but has a more sustained and long-lasting effect on rabbits with darker iris color. Therefore, I aim to investigate if the drug has less therapeutic efficacy on light-irides subjects. and see if […]
In arthropods and vertebrates, Hox genes determine how an organism develops along the axis running from its head to its tail. Little is known of Hox function outside of these standard animal models, but studies in annelids (segmented worms) suggest that Hox genes not only play a conserved role in embryonic patterning, but are also deployed in ways specific to annelids. For example, hox3 is expressed around the posterior growth zone (PGZ), from which all new segments arise. I hypothesize that hox3 is a stem cell marker in annelids that is necessary for PGZ activity. I will examine this hypothesis with expression analysis and CRISPR mutagenesis of hox3 in Helobdella austinensis, a leech. My proposed research represents one of the first analyses of Hox function in a segmented animal that is not an arthropod or a vertebrate; it thus adds to our understanding of how developmental mechanisms evolved during the […]
Up to half of Wilsons disease patients suffer from sleep disorders, including poor sleep quality, REM behavioral disorders (RBD), and cataplexy. However, the neural basis of these symptoms is poorly understood. My project this summer is to determine whether the ATP7B-/- knockout mouse is a good model system for studying the sleep disorders manifested in Wilsons disease, especially in the context of neural pathways involving copper homeostasis. Using automated sleep scoring methods, we will quantify sleep signatures in ATP7B-/- knockout and wildtype control mice. The brain copper changes in recorded mice will then be analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to create a map of copper distribution from which key brain regions associated with sleep changes can be identified. The ATP7B-/- knockout mouse has the potential to be incredibly useful in studying neurological symptoms and sleep disorders in Wilsons disease patients, as well as for REM […]
Suppose that we have a (finite or infinite) series of independent, identically distributed real-valued random variables (increments of time). From this series, we can form a random walk. We can consider the partial sums of this series and analyze the average value of the walk the partial sum divided by the number of increments up to that point at each of its time increments. This project is focused on studying the distribution of the maximum average value of a random walk through a variety of computational algorithms. While there already exists an explicit formula for the probability that the maximum average value is at most any given real number 0 x 1, this formula presents computational challenges for small values of x. What is especially interesting is the asymptotic aspect: how quickly does the probability that the maximal average is at most x approach zero as x approaches zero from […]
Contactin-associated protein-like 2 (CNTNAP2) mutations are strongly associated with autism spectrum disorder, which presents with repetitive behaviors. Research has shown that mice lacking CNTNAP2 exhibit decreased numbers of GABAergic interneurons throughout the brain, and that the number and function of these interneurons in the striatum are associated with the presentation of repetitive behaviors. Recent work has shown that enriched environment rearing restores GABAergic interneuron numbers in the striatum and rescues behavioral deficits in rodent models of neuropsychiatric disorders. I will be looking at how different rearing conditions affect striatal gene expression and behaviors in CNTNAP2 knockout mice. My project will explore the interactions between genes and the environment, particularly the potential for environmental aspects to alter striatal interneuron cell types and the presence of repetitive behaviors. The goal of my project is to help provide insight into how environmental factors may influence neurodevelopmental disorders.
In humans, Positive Transcription Elongation Factor b (P-TEFb) is an RNA Polymerase II regulator crucial for proper gene expression. To execute its regulatory function, P-TEFb itself is precisely regulated via reversible interactions with an snRNP complex. Using biochemical techniques, past studies have confirmed LARP7, HEXIM1, and BRD4 to be protein partners of P-TEFb. My project aims to study the dynamic regulatory role of known protein partners LARP7, HEXIM1, and BRD4 in P-TEFb regulation. I will apply a new technique called proximity-assisted photoactivation (PAPA) to single particle tracking (SPT) and live cell imaging in order to examine protein-protein interactions between P-TEFb and each protein partner in human osteosarcoma cells. PAPA involves a sender fluorophore reactivating a receiver fluorophore when the two are in proximity. By tagging P-TEFb and each partner with these fluorophores, PAPA can be used to detect their interaction corresponding to the sub-population of protein complexes showing sender […]
Psychedelics have been used medicinally for thousands of years by Native Americans, but research into their clinical effects and mechanisms was prematurely halted in the 1960s. Exploration of the effects of psychedelics is long overdue. Recent studies have found that single doses of psychedelics can have positive, long-lasting effects, but very few studies examine psychedelic effects on behavior. My project aims to discover how psychedelics influence associative learning behavior. Associative learning involves learning the association between a cue and an outcome. I hypothesize that mice treated with psychedelics will become better at associative learning. To test this hypothesis, I will condition mice in an enriched environment with novel flooring and then condition them in a non-enriched environment with a different flooring. Both conditions will isolate the mouse; the enriched environment is like a moude playground, whereas the non-enriched environment is a boring empty cage. If mice have learned the […]