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, 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 combat 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 synchronized to encode and store episodic 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 the health professions.
Our passion and dedication to science have recently led us to make several groundbreaking discoveries. We have revealed that burst synchronization of primed hippocampal neurons is crucial (probably essential) for learning and forming trace fear memory (highlights: https://neurosciencenews.com/memory-learning-cell-synchronization-15649/; https://directorsblog.nih.gov/2021/03/25/the-synchronicity-of-memory/). We have developed the first method to quantitatively measure in vivo hippocampal neuronal activity hierarchy, and we initially reported that the non-linear weighted synaptic conductance, likely mediated by the NMDARs, regulates the development and maintenance of neuronal activity hierarchy (Zhou et al., 2023 bioRxiv, 523038). We have introduced the concept that neuronal and astrocytic primary cilia exhibit a dichotomy, as distinguished by their morphological dynamics, major signaling pathways, key molecular components, and functionality, as well as disease associations (Sterpka et al., 2020). We are the first to discover that neuronal primary cilia direct postnatal principal cell positioning, and principal neurons in the cerebral cortex undergo a previously unnoticed "reverse migration" for neuron positioning and cortical lamination (Yang et al., 2021 bioRxiv, 473383).
Research Approaches: molecular biology, cellular imaging, behavioral analysis, patch-clamp electrophysiology, EEG/EMG recording, in vivo deep-brain 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, Sahar Jamialahmadi, Jordan Tropey, Jung-Kai Lin, Jenn Wang, and Sierra Walsh.
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.
