Our brains integrate environmental cues with memories of past experiences to select appropriate behavioral responses. The medial prefrontal cortex (mPFC) plays a key role in analyzing the emotional significance of stimuli and thus contributes to many adaptive behaviors including fear memory retrieval, extinction, and avoidance. mPFC is broadly connected with the limbic system, association cortices, and neuromodulatory systems, and individual mPFC projections have been linked to specific behaviors. However, little is known about the relative functions of mPFC neurons that participate in different behaviors. Furthermore, mPFC undergoes a protracted synaptic development that is particularly vulnerable to psychiatric diseases including fear and anxiety disorders, depression, and autism, but it is unclear how its circuits form. Research in the DeNardo lab aims to understand how mPFC is organized to promote specific behaviors. Do particular classes of mPFC projection neurons mediate different behaviors, or do the same classes of mPFC neurons adapt their function to promote different behavioral outcomes? How are these circuits assembled during development? Using innovative viral-genetic tools, novel transgenic mice, and whole-brain imaging technologies, we aim to define the connectivity and function of mPFC cells underlying adaptive behaviors and to identify molecular cues that wire these circuits during development.
Laura DeNardo, Ph.D. is an Assistant Professor in the Department of Physiology in the David Geffen School of Medicine at UCLA. She received a dual BA in Molecular and Cell Biology and Art Practice from UC Berkeley in 2007. She went on to receive a Ph.D. in Neurosciences from UC San Diego, where she worked with Dr. Anirvan Ghosh. As a graduate student, she elucidated mechanisms governing the development and function of hippocampal synapses. Her work identified a key molecular mechanism by which individual neurons can independently regulate the development of specific classes of synapses in distinct dendritic compartments. Beginning in 2013, she carried out her postdoctoral fellowship with Dr. Liqun Luo at Stanford University. As a postdoc, Dr. DeNardo used new viral-genetic tools to map cortical microcircuits. Focusing on the medial prefrontal cortex (mPFC), she identified important departures from the canonical microcircuit organization that has been well-characterized in sensory cortices. To understand how neuronal circuits control behavior, she developed a new knock-in mouse for activity-dependent genetic labeling (TRAP2) that is being widely adopted by the global Neuroscience community. Using TRAP2, she has elucidated the organization and function of mPFC circuits that contribute to long-term memory. Dr. DeNardo will open her lab at UCLA in January, 2019.
A selected list of publications:
- Laura A DeNardo, Cindy D Liu, William E Allen, Eliza L Adams, Drew Friedmann, Ehsan Dadgar-Kiani, Lisa Fu, Casey J Guenthner, Jin Hyung Lee, Marc Tessier-Lavigne, Liqun Luo Temporal Evolution of Cortical Ensembles Promoting Remote Memory Retrieval , 2018; .
- Berns Dominic S, DeNardo Laura A, Pederick Daniel T, Luo Liqun Teneurin-3 controls topographic circuit assembly in the hippocampus Nature, 2018; 554(7692): 328-333.
- Savas Jeffrey N, Wang Yi-Zhi, DeNardo Laura A, Martinez-Bartolome Salvador, McClatchy Daniel B, Hark Timothy J, Shanks Natalie F, Cozzolino Kira A, Lavallée-Adam Mathieu, Smukowski Samuel N, Park Sung Kyu, Kelly Jeffery W, Koo Edward H, Nakagawa Terunaga, Masliah Eliezer, Ghosh Anirvan, Yates John R Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer’s Disease-like Pathology Cell reports, 2017; 21(9): 2614-2627.
- Allen William E, DeNardo Laura A, Chen Michael Z, Liu Cindy D, Loh Kyle M, Fenno Lief E, Ramakrishnan Charu, Deisseroth Karl, Luo Liqun Thirst-associated preoptic neurons encode an aversive motivational drive Science (New York, N.Y.), 2017; 357(6356): 1149-1155.
- DeNardo Laura, Luo Liqun Genetic strategies to access activated neurons Current opinion in neurobiology, 2017; 45(6356): 121-129.
- Savas JN, Ribeiro LF, Wierda KD, Wright R, DeNardo-Wilke LA, Chamma I, Wang Yi-Zhi, Zemla R, Lavallee- Adam M, Vennekens KM, O’Sullivan ML, Antonios JK, Hall EA, Thoumine O, Attie AD, Yates JR, Ghosh A, De Wit J The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA receptors, Neuron, 2015; 87: 764-80.
- DeNardo Laura A, Berns Dominic S, DeLoach Katherine, Luo Liqun Connectivity of mouse somatosensory and prefrontal cortex examined with trans-synaptic tracing Nature neuroscience, 2015; 18(11): 1687-1697.
- DeNardo Laura A, de Wit Joris, Otto-Hitt Stefanie, Ghosh Anirvan NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons Neuron, 2012; 76(4): 762-75.
- Wilke Scott A, Hall Benjamin J, Antonios Joseph K, Denardo Laura A, Otto Stefanie, Yuan Bo, Chen Fading, Robbins Elissa M, Tiglio Katie, Williams Megan E, Qiu Zilong, Biederer Thomas, Ghosh Anirvan NeuroD2 regulates the development of hippocampal mossy fiber synapses Neural development, 2012; 7(4): 9.