Our laboratory has two major research interests: hippocampus-dependent memory formation and primary cilia. “Memory is the glue that holds our mental life together” (Kandel et al., 2014). Aberrant “glue” affects our cognitive capacities and causes many cognitive dysfunction-related disorders, including dementia, amnesia, post-traumatic stress disorder (PTSD), intellectual disability, and autism spectrum disorder (ASD). Unraveling the mechanisms underlying learning and hippocampus-dependent memory formation is needed not only to understand how we acquire and retain experiences, skills, and knowledge, but also to develop mechanism-based therapies to combat these cognitive dysfunction-related disorders.
Primary cilia are centriole-derived “cellular antennae” that detect many extracellular signals ranging from neurotransmitters to hormones and morphogens, and thus regulate a variety of physiological functions including sensation, cognition, and development. Human diseases caused by malfunctions in primary cilia encompass developmental disorders, neurodegeneration, and cognitive impairment. To date, primary cilia in the brain are under-studied, and we know very little about how neuronal primary cilia affect neuronal activity and memory formation. Both neurons and astrocytes possess a single primary cilium. We are the first to propose that neuronal and astrocytic primary cilia exhibit a dichotomy, as distinguished by their morphological dynamics, signaling pathways, key molecular components (i.e., marker proteins), nanoscale structure, and functionality, as well as disease associations. We have also discovered that neuronal primary cilia regulate the positioning of pyramidal cells to CA1 sublayers and late-born pyramidal cells undergo a "reverse movement" for final neuronal positioning (Yang et al., bioRxiv, 10.1101/2021.12.21.473383).
The first goal of our research is to determine how primary cilia signals affect neuronal priming in the adult brain and postnatal neurodevelopment, and thereby modulates hippocampus-dependent memory formation. The second goal is to understand how primary cilia sense changes in the brain and impact neural function in health and disease conditions. My long-term vision is to build bridges between fundamental research in neuroscience and translational research, facilitating the development of novel therapies to treat cognitive dysfunction-related disorders. My vision also includes increasing efforts to train the next generation of neuroscientists and bio-technologists, and foster the career growth of pre-health science majors.
Key Words: Primary Cilia, Adenylyl Cyclases, Hippocampal Memory Formation, Neural Synchronization, Neuronal Positioning, and Cognitive Dysfunction-Related Disorders
Research Approaches: molecular biology, cellular imaging, behavioral analysis, patch-clamp electrophysiology, EEG/EMG recording, in vivo deep-brain fiber-optic calcium imaging in freely behaving mice, pharmacological tools, viral vector delivery, and transgenic animal models
Lab Members: Yuxin Zhou, Juan Yang, Liyan Qiu, Soheila Mirhosseiniardakani, Kostandina (Dina) Bicja, Jordan Tropey, Jung-Kai Lin, Jenn Wang, and Sierra Rose Walsh.
Funding: Our research is supported by National Institutes of Health Grants K01AG054729, P20GM113131, R15MH126317, and R15MH125305, Cole Neuroscience and Behavioral Faculty Research Awards, CoRE PRP awards, UNH teaching assistantships and Summer TA Fellowships, and awards from the Hamel Center for Undergraduate Research.
Research Highlight: Burst Synchronization of Primed Hippocampal Neurons Critical For Learning and Forming Memories.
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201902274R
https://neurosciencenews.com/memory-learning-cell-synchronization-15649/
https://directorsblog.nih.gov/2021/03/25/the-synchronicity-of-memory/ - Featured on NIH Director's Blog
The lab is recruiting highly motivated graduate and undergraduate students.
