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, autism spectrum disorder (ASD), and major depressive disorder (MDD). 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 function to detect numerous signals ranging from photons and odorants to neurotransmitters, hormones, and morphogens, and thus regulate a variety of physiological functions including sensation, cognition, and development. Human diseases caused by malfunctions in primary cilia include developmental disorders, polycystic kidney disease, obesity, neurodegeneration, and cognitive impairment. In the central nervous system, both neurons and astrocytes possess a single primary cilium. We have recently proposed 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. In general, primary cilia in the brain are under-studied, and it remains to be elucidated how primary cilia modulate neuronal function and affect learning and declarative memory formation.
The first goal of my research is to determine how neuronal signal, particularly ciliary signaling, affects neuronal excitability and gene expression, and thereby modulates hippocampus-dependent memory formation. The second goal is to understand how neuronal and astrocytic primary cilia sense changes in the brain and modulate 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 growth of pre-health sciences majors.
Key Words: Primary Cilia, Adenylyl Cyclases, Hippocampus-Dependent Memory Formation, Neural Synchronization, Cognitive Dysfunction-Related Disorders
Research Approaches: molecular biology, biochemical analysis, cellular imaging, behavioral analysis, patch-clamp electrophysiology, EEG/EMG recording, multi-channel unitary recording, in vivo deep-brain fiber-optic calcium imaging in freely behaving mice, optogenetics, pharmacological tools, viral vector delivery, and transgenic animal models
Lab Members: Yuxin Zhou, Matthew Strobel, Ashley Sterpka, Juan Yang, Liyan Qiu, Victoria Denovellis, Kelsey MacCallum, Kostandina (Dina) Bicja, Brendon Lewis, and Holly Farrell
Funding: Our research is funded by National Institutes of Health Grants R21MH105746, K01AG054729, and P20GM113131, R15MH126317, Cole Neuroscience and Behavioral Faculty Research Awards, a CoRE PRP award, UNH teaching assistantships and Summer TA Fellowships, and awards from the Hamel Center for Undergraduate Research.
Research Highlight: UNH Researchers Find Burst Synchronization of Memory Cells 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
"Impact, Not Impact Factor" (by Inder M. Verma)
