In a nutshell, I am interested in understanding the cellular and neurochemical bases of individuality. I am also interested in understanding how experience during youth shapes a person’s personality and mental capacities, enabling the person to pursue many adaptive behaviors or become trapped by compulsive, maladaptive behaviors. Most recently, I have been using an animal model of anorexia nervosa, called activity-based anorexia to fulfill my curiosity. Approximately half of adolescent female rodents that face restricted food access respond paradoxically by increasing wheel running, thereby exacerbating energy expenditure. Unless removed from the environment of wheel access, these animals will perish. Other animals suppress their wheel running, thereby conserving energy and sustaining healthy body weight. Looking into their brain with an electron microscope, I have been able to identify neural circuits and molecular features at synapses in the hippocampus, prefrontal cortex and amygdala that correlate with individual differences in vulnerability to the stress-induced anxiety that is caused by food restriction. By using multiplexed chemogenetics to activate OR suppress discrete populations of neurons, I am learning causal links between activity of specific brain pathways and maladaptive behaviors. These studies, together, point to plasticity of the GABAergic system in prefrontal cortex, hippocampus and amygdala as key features differentiating individual differences in vulnerability to stress-evoked anxiety that lead to maladaptive behaviors. It is my hope that these clues will help design better pharmacological treatments for mental illnesses. When not in the lab or home writing, I love to cook, stroll around the neighborhood, read the NY Times and watch movies. Although I like to watch current block busters, my favorite director still is Werner Herzog, my favorite cartoonist still is Miyazaki and my favorite cartoon characters still are Tottoro and Nausicaa.
My teaching activities. I am passionate about teaching. For this reason, I am happy to have received the Distinguished Teaching Award from NYU in 2021 and to be a two-time recipient of the Golden Dozen Award in Teaching. Please check out my Philosophy of Teaching here.
A bit more about my research….My current research continues to use electron microscopic techniques to examine the cellular bases of interaction between transmitters and receptors that are thought to have important roles in synaptic plasticity. By using the electron microscope, we have observed that neurotransmitter receptors are brought to the pre- and postsynaptic membrane in an activity-dependent manner. This response is measurable within tens of minutes within adult cortices. We have a hunch that cytoskeletal proteins are involved in the activity-dependent trafficking of synaptic molecules within dendritic spines and axon terminals. Thus, we are exploring the role of two candidate molecules that link the recruitment of synaptic molecules to newly forming synapses: drebrin, for the postsynaptic membrane and neurexin, for the axon terminals.
I have two other interests for which research is just beginning. One is to understand the cellular and molecular mechanisms underlying ketamine’s action as an antidepressant and possibly also as a pharmacotherapy for anorexia nervosa. I am using the activity-based anorexia model to explore this point. The other is the cellular basis of individual differences in the motivation to exercise. We all know that exercise is good for our body and brain but some of us (me included) find it difficult to put in the time to exercise. I have observed that mice with the experience of activity-based anorexia during adolescence continue to be avid voluntary runners, even when they become aged and even if they are not hungry. Is there a neural ensemble that becomes solidified, sustaining life-long “love” for exercise? If so, what are the molecular mechanisms that solidify this neural ensemble? In order to answer this question, I am exploring ways to tag neural ensembles that are activated while exercising as adolescents so that I can evaluate how their synaptic connectivities are sustained through life.
For a 90 second introduction to my research, please check out this video.
My academic history. My interest in neuroscience stems from my personal history of having grown up in LA, Tokyo and New York, which caused me to lose and regain my native tongue twice. I wondered what is going on in the brain to enable me to learn a new language so easily as a young child while the same task became so difficult as an adult. This question led to my doctoral research project, which was to look for the cellular basis for the critical period during development that enables sensory experience to translate into stable neuronal connections. I pursued this research in the laboratory of Dr. Philip Siekevitz at the Rockefeller University. I showed that there is a functional link between neuronal activity, second messengers, and phosphorylation of a cytoskeletal protein–MAP2–during the critical period for visual cortex development. These results suggest that neuronal plasticity may depend on the malleability of cell shape, which, in turn, is dependent on the state of phosphorylation of cytoskeletal proteins. For this work, I received a Ph.D. degree in 1985 and had fun writing an article for a popular science magazine, Scientific American.
For my postdoctoral training, I joined the laboratory of Dr. Virginia M. Pickel in the Department of Neurology and Neuroscience, The Weill Cornell Medical College. During this period, I learned how to visualize two types of molecules simultaneously at a level of resolution afforded by an electron microscope, so that molecular interactions at newly forming and well- established synapses could be probed. Using this technique, I have shown that (1) catecholamines diffuse beyond the synaptic cleft to activate receptors at sites that lack ultrastructural features of synapses; (2) glia extend fine processes around glutamatergic synapses to aid in converting neuronally released glutamate to its non-toxic form, glutamine; (3) the novel neuronal messenger–nitric oxide–can be generated both pre- and postsynaptically and within spines expressing NMDA receptors; and (4) NMDA receptors occur both pre- and postsynaptically; (5) NMDA receptor clusters can be found at nonsynaptic sites of dendritic shafts and somata during early life, prior to the arrival of afferents. I also began training to become an instructor of neurobiology while at The Weill Cornell Medical College.