Chiye Aoki

Adolescent brain plasticity, individual differences in vulnerability and resilience to mental illnesses, including eating disorders and anxiety, neural circuits, synaptic molecules, electron microscopy.

The long-term goal of my research has been to understand the cell biological mechanisms underlying plasticity and stability of neurons. The mammalian brain undergoes dramatic developmental changes after birth, yielding neural functions that reflect the experience of early life. Once mature, the pathways of the brain become more stable while maintaining a certain degree of plasticity. I have learned that this developmental process is prolonged into adolescence for brain regions that are highly associational, such as the prefrontal cortex and hippocampus. 

Currently, I am most interested in understanding the cellular bases of resilience gained when adolescent individuals are placed in stressful environments. I am focusing my research on plasticity of synaptic circuits within the prefrontal cortex and hippocampus, using the paradigm of food restriction-evoked stress which elicits excessive exercise and severe body weight loss in rodents, much as is seen among patients diagnosed with anorexia nervosa. The approach of analyzing synaptic properties in these brain regions across individuals with varying degrees of resilience has shown interesting correlates, providing clues about molecules within circuits that influence maladaptive behavior and resilience. I take these clues to interrogate the circuits and molecules involved in the generation of maladaptive behavior, using knockdown and knockout of genes, pharmacology and chemogenetic modulations. I am also exploring the synaptic mechanisms underlying the ameliorative properties of sub-anesthetic doses of ketamine against anorexia-like maladaptive behaviors.  

Chiye Aoki and Adrienne N. Santiago (2022) Pathway-specific GABAergic inhibition contributes to the gain of resilience against anorexia-like behavior of adolescent female mice. Frontiers in Behavioral Neuroscience, In Press, PDF . DOI: 10.3389/fnbeh.2022.990354.

Adrienne N. Santiago, Emily A. Makowicz, Muzi (Andrew) Du and Chiye Aoki. (2021) Food restriction engages prefrontal corticostriatal cells and local microcircuitry to drive the decision to run versus conserve energy. Cerebral Cortex, 31(6) 2868-2885. PDF DOI: 10.1093/cercor/bhaa394 Suppl Material

Chowdhury, Tara G., Wable, Gauri S., Chen,Yi-Wen, Tateyama,Kei, Yu, Irene, Wang, Jia-Yi , Reyes, Alex D. and Aoki, Chiye. (2018) Voluntary wheel running exercise evoked by food-restriction stress exacerbates weight loss of adolescent female rats but also promotes resilience by enhancing GABAergic inhibition of pyramidal neurons in the dorsal hippocampus. Cerebral Cortex, 29(10):4035-4049. PDF doi: 10.1093/cercor/bhy283. PMCID:PMC6931273

Chen,Yi-Wen, Sherpa, Ang D. and C Aoki. (2018) Single injection of ketamine during mid-adolescence promotes long-lasting resilience to activity-based anorexia in female mice by increasing food intake and attenuating hyperactivity as well as anxiety-like behavior. International J of Eating Disorders, 51(7354) July 16, 2018. PDF DOI: 10.1002/eat.22937 PMID: 30102796

Shen H., Sabaliauskas N., Sherpa A., Fenton A. A., Stelzer, A, Aoki C., and Smith S. S. (2010). A Critical Role for α4-Beta-Delta GABAA Receptors in Shaping Learning Deficits at Puberty in Mice. PDF  Science, 327: 1515-1518