Positions

Overview

  • 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 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 health professions.

    Our dedications to science have recently led us to make several important 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., bioRxiv, 523038 v2). Guided by primary cilia directionality, we discover that principal neurons in the cerebral cortex undergo a previously unnoticed, slow but substantial "reverse migration" for postnatal positioning and cortical lamination (Yang et al., bioRxiv, 473383v5).

    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: Sumaya Akter, Liyan Qiu, Soheila Mirhosseiniardakani, Jenn Wang, Sahar Jamialahmadi, Kevin Jiang, Jemma Glenn Wilxon, Christopher Boujaoude 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.
  • Selected Publications

    Academic Article

    Year Title
    2023 Hypoxia sensing requires H2S-dependent persulfidation of olfactory receptor 78.Science advances.  9:eadf3026. 2023
    2023 Activity Hierarchy Measurement to Establish Trace Memory-eligible "Primed" Neurons.bioRxiv2023
    2021 Primary Cilia Directionality Reveals a Slow Reverse Movement of Principal Neurons for Postnatal Positioning and Lamina Refinement in the Cerebral Cortex 2021
    2020 Acid-Sensing Ion Channels Contribute to Type III Adenylyl Cyclase-Independent Acid Sensing of Mouse Olfactory Sensory Neurons.Molecular Neurobiology.  57:3042-3056. 2020
    2020 Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults.Molecular Brain.  13:28. 2020
    2020 Induction of activity synchronization among primed hippocampal neurons out of random dynamics is key for trace memory formation and retrieval.The FASEB Journal.  34:3658-3676. 2020
    2019 Induction of Activity Synchronization among Primed Hippocampal Neurons out of Random Dynamics is Key for Trace Memory Formation and RetrievalThe FASEB Journal.  in press. 2019
    2019 Comparative Phosphoproteomic Profiling of Type III Adenylyl Cyclase Knockout and Control, Male, and Female Mice.Frontiers in Cellular Neuroscience.  13:34. 2019
    2019 Dynamics of a hippocampal neuronal ensemble encoding trace fear memory revealed by in vivo Ca2+ imaging.PLoS ONE.  14:e0219152. 2019
    2016 Ablation of Type III Adenylyl Cyclase in Mice Causes Reduced Neuronal Activity, Altered Sleep Pattern, and Depression-like Phenotypes.Biological Psychiatry.  80:836-848. 2016
    2016 Disruption of type 3 adenylyl cyclase expression in the hypothalamus leads to obesity.Integr Obes Diabetes.  2:225-228. 2016
    2015 An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors.Current Biology.  25:2503-2512. 2015
    2015 Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition.The Journal of Neuroscience.  35:339-351. 2015
    2015 The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb.PLoS ONE.  10:e0122057. 2015
    2014 Genetic disruption of the core circadian clock impairs hippocampus-dependent memory.Learning and Memory.  21:417-423. 2014
    2013 Electroolfactogram (EOG) Recording in the Mouse Main Olfactory Epithelium.Bio Protoc.  3:e789. 2013
    2013 Isoflurane regulates atypical type-A γ-aminobutyric acid receptors in alveolar type II epithelial cells.Anesthesiology.  118:1065-1075. 2013
    2012 Stimulation of electro-olfactogram responses in the main olfactory epithelia by airflow depends on the type 3 adenylyl cyclase.The Journal of Neuroscience.  32:15769-15778. 2012
    2011 An anti-coagulation agent Futhan preferentially targets GABA(A) receptors in lungepithelia: implication in treating asthma.International Journal of Physiology, Pathophysiology and Pharmacology.  3:249-256. 2011
    2011 Functional modifications of acid-sensing ion channels by ligand-gated chloride channels.PLoS ONE.  6:e21970. 2011
    2010 Design and screening of ASIC inhibitors based on aromatic diamidines for combating neurological disorders.European Journal of Pharmacology.  648:15-23. 2010
    2010 The modulation of TRPM7 currents by nafamostat mesilate depends directly upon extracellular concentrations of divalent cations.Molecular Brain.  3:38. 2010
    2010 Diarylamidines: high potency inhibitors of acid-sensing ion channels.Neuropharmacology.  58:1045-1053. 2010
    2009 Platelet-derived growth factor selectively inhibits NR2B-containing N-methyl-D-aspartate receptors in CA1 hippocampal neurons.Journal of Biological Chemistry.  284:8054-8063. 2009
    2008 Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.Journal of Biological Chemistry.  283:572-581. 2008
    2007 Zebrafish acid-sensing ion channel (ASIC) 4, characterization of homo- and heteromeric channels, and identification of regions important for activation by H+.Journal of Biological Chemistry.  282:30406-30413. 2007
    2007 Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.The Journal of Physiology.  579:657-670. 2007
    2006 Strong modulation by RFamide neuropeptides of the ASIC1b/3 heteromer in competition with extracellular calcium.Neuropharmacology.  50:964-974. 2006
    2006 Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent.Journal of General Physiology.  127:267-276. 2006
    2005 The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity.Journal of General Physiology.  126:71-79. 2005
    2002 [Cloning expression of a novel human protein-disulfide isomerase like cDNA].Shengwu Yixue Gongchengxue Zazhi/Journal of Biomedical Engineering.  19:459-462. 2002

    Article

    Year Title
    2024 Temporal Ablation of Primary Cilia Impairs Brainwave Patterns Implicated in Memory Formation 2024

    Other Research Activities

    Teaching Activities

  • Doctoral Thesis Taught course 2023
  • Honors Senior Thesis Taught course 2023
  • Doctoral Thesis Taught course 2022
  • Honor/Intro Biol: Mol/Cellular Taught course 2022
  • Honors Senior Thesis Taught course 2022
  • Intro to Research in Life Sci Taught course 2022
  • Invest in Molecular & Cell Bio Taught course 2022
  • Doctoral Thesis Taught course 2022
  • Honors Senior Thesis Taught course 2022
  • Pharmacology Taught course 2022
  • Senior Honors Thesis Taught course 2022
  • Advanced Research Experience Taught course 2021
  • Doctoral Thesis Taught course 2021
  • Honor/Intro Biol: Mol/Cellular Taught course 2021
  • Honors Senior Thesis Taught course 2021
  • Intro to Research in Life Sci Taught course 2021
  • Doctoral Thesis Taught course 2021
  • Pharmacology Taught course 2021
  • Pharmacology Taught course 2021
  • Rsrch Exp/MCBS Taught course 2021
  • Doctoral Thesis Taught course 2020
  • Intro Biol: Mol/Cellular/Hon Taught course 2020
  • Intro to Research in Life Sci Taught course 2020
  • Doctoral Thesis Taught course 2020
  • Pharmacology Taught course 2020
  • Rsrch Exp/MCBS Taught course 2020
  • Senior Honors Thesis Taught course 2020
  • Doctoral Thesis Taught course 2019
  • Hon/Principles of Biol I Lab Taught course 2019
  • Honors/Intro Biol:Mol/Cellular Taught course 2019
  • Intro to Research in Life Sci Taught course 2019
  • Rsrch Exp/MCBS Taught course 2019
  • Doctoral Thesis Taught course 2019
  • Pharmacology Taught course 2019
  • Senior Honors Thesis Taught course 2019
  • Doctoral Thesis Taught course 2018
  • Honors/Intro Biol:Mol/Cellular Taught course 2018
  • Senior Honors Thesis Taught course 2018
  • Adv Rsrch Exp/MCBS Taught course 2018
  • Doctoral Research Taught course 2018
  • Doctoral Research Taught course 2018
  • Pharmacology Taught course 2018
  • Rsrch Exp/MCBS Taught course 2018
  • Honors/Intro Biol:Mol/Cellular Taught course 2017
  • Honors/Intro Biol:Mol/Cellular Taught course 2017
  • Honors/Intro Biol:Mol/Cellular Taught course 2017
  • Rsrch Exp/MCBS Taught course 2017
  • Rsrch Exp/MCBS Taught course 2017
  • Adv Rsrch Exp/MCBS Taught course 2017
  • Pharmacology Taught course 2017
  • Rsrch Exp/MCBS Taught course 2017
  • Honors Senior Thesis Taught course 2016
  • Rsrch Exp/MCBS Taught course 2016
  • Rsrch Exp/MCBS Taught course 2016
  • Education And Training

  • B.S. Biology, Nanchang University
  • M.S. Genetics, Fudan University
  • Ph.D. Physiology, University of Tuebingen
  • Full Name

  • Xuanmao Chen