Our laboratory has two major research interests: hippocampal 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 numerous cognitive dysfunction-related disorders, including dementia, amnesia, post-traumatic stress disorder (PTSD), intellectual disability, depression, schizophrenia, and autism spectrum disorder (ASD). Unraveling the mechanisms underlying learning and memory formation is needed not only to understand how we acquire and retain experiences and knowledge, but also to develop mechanism-based therapies to treat these disorders. Primary cilia are centriole-derived “cellular antennae” that detect many extracellular signals including hormones and morphogens and regulate a variety of physiological functions including sensation, cognition, and development. Human diseases caused by malfunctions in primary cilia encompass developmental disorders, obesity, neurodegeneration, psychiatric disorders, and cognitive impairments. To date, little is known about how neuronal primary cilia affect postnatal development, neural function in the adult brain, and memory formation.
The first goal of our research is to understand how a fraction of neurons in the cerebral cortex are recruited and interact with each other to encode and store associative memory. The second goal is to determine how ciliary signaling affects postnatal neurodevelopment and neuronal function in the adult brain, and thereby modulates memory formation. Our long-term vision is to build bridges connecting fundamental neuroscience research with translational medicine, facilitating the development of novel therapies to treat cognitive dysfunction-related disorders. Our vision also includes increasing efforts to train the next-generation of deep thinkers for science, while also supporting the growth of individuals pursuing careers in biotech and health professions.
Our passion and dedication to sciences have led us to make multiple fundamental discoveries. We have revealed that burst synchronization of primed hippocampal neurons is crucial (probably essential) for learning and forming trace fear memory (Zhou et al., FASEB J. 2000). We have developed the first method to quantitatively measure real-time hippocampal neuronal activity hierarchy. We initially reported that the non-linear NMDAR-mediated synaptic conductance controls the development and maintenance of neural activity hierarchy and loss of control in hierarchy leads to dissociation and psychosis (Zhou et al., bioRxiv, 523038v4). Guided by neuronal cilia directionality, we have discovered that principal neurons in the cerebral cortex, including the hippocampal CA1, subiculum, and neocortex, undergo a previously unnoticed, slow but substantial "reverse movement" for postnatal cell positioning and cortical lamination (Yang et al., bioRxiv, 473383v6).
Research Approaches: molecular biology, confocal molecular imaging, behavioral analysis, patch-clamp electrophysiology, EEG/EMG deep-electrode recording, in vivo deep-brain calcium imaging on freely behaving mice, pharmacological tools, viral vector delivery, and transgenic animal models
Lab Members: Qin An, Sumaya Akter, Soheila Mirhosseiniardakani, Sierra Walsh, Jenn Wang, Liyan Qiu, Kevin Jiang, Jemma Glenn Wilxon, Elliot Meine, Jacob Dumais, and Christopher Boujaoude.
Funding: Our research is supported by NIH Grants K01AG054729, P20GM113131, R15MH126317, and R15MH125305, COLE Research Awards, CoRE PRP awards, UNH Teaching Assistantships, Summer TA Fellowships and Dissertation Year Fellowships, and awards from the Hamel Center for Undergraduate Research.
