The DeNardo Lab
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 promoting adaptive responses. We are particularly interested in how mPFC controls adaptive threat responding. mPFC is broadly interconnected with the limbic system, association cortices, and neuromodulatory systems, and individual mPFC connections have been linked to specific behaviors. However, little is known about the specific connectivity and function of mPFC neurons that contribute to distinct adaptive behaviors. Furthermore, mPFC undergoes a prolonged development that renders its circuitry vulnerable to genetic and environmental insults occurring early in life. As a result, mPFC dysfunction is linked to numerous psychiatric diseases including fear and anxiety disorders and depression. Yet remains it unclear how mPFC circuits develop and how their maturation can be perturbed by disease risk factors. We will address these questions using cutting-edge tools in systems- and cellular-level Neuroscience. We are seeking enthusiastic and motivated scientists to join the team!
organization of mpfc circuits that give rise to adaptive behaviors
Using optogenetics, viral tracing, and the TRAP2 mouse for activity-dependent genetic labeling, we define the causal function and underlying connectivity of mPFC neurons that contribute to learned threat responses across the lifespan.
mapping the activity patterns underlying ADAPTIVE AND MALADAPTIVE THREAT RESPONSES
Using the fiber photometry and UCLA Miniscopes, we explore mPFC activity patterns underlying learned threat responses including avoidance and conditioned fear in the mouse.
how are mpfc circuits for adaptive behaviors wired during development?
Using RNAseq and viral tracing coupled to cell-type specific gene knockout, we will identify molecular cues that wire mPFC fear circuits during development, and ultimately explore the consequences of genetic mutations that increase risk for disease.
Publications
2023
2022
Blagburn-Blanco SV, Chapelle MS, De Biase LM# and DeNardo LA#. Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex (2022) Frontiers in Molecular Neuroscience https://doi.org/10.3389/fnmol.2022.965756
2021
Choe KY, Bethlehem RAI, Safrin M, Dong H, Salman E, Li Y, Grinevich V, Golshani P, DeNardo LA, Penagarikano O, Harris NG, Geschwind DH. Oxytocin normalizes altered circuit connectivity for social rescue of the Cntnap2 knockout mouse (2021) Neuron https://doi.org/10.1016/j.neuron.2021.11.031
2020
Tasaka G, Feigin L, Maor I, Groysman M, DeNardo LA, Schiavo JK, Froemke RC, Luo L, Mizrahi A. The temporal association cortex plays a key role in auditory-driven maternal plasticity (2020) Neuron https://doi.org/10.1016/j.neuron.2020.05.004
Lee HS, Yamazaki R, Wang D, Arthaud S, Fort P, DeNardo LA, Luppi PH. Targeted recombination in active populations as a new mouse genetic model to study sleep-active neuronal populations: Demonstration that Lhx6+ neurons in the ventral zona incerta are activated during paradoxical sleep hypersomnia (2020) Journal of Sleep Research https://doi.org/10.1111/jsr.12976
2019
DeNardo LA, Liu CD, Allen WE, Adams EL, Friedmann D, Fu LX, Guenthner CJ, Tessier-Lavigne M, Luo L. Temporal Evolution in Cortical Ensembles Mediating Remote Memory Retrieval (2019) Nature Neuroscience https://doi.org/10.1038/s41593-018-0318-7
2018
2017
2015
2012