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 thus contributes to many adaptive behaviors including fear memory retrieval, extinction, and avoidance. 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 protracted synaptic development that is particularly vulnerable to psychiatric diseases including fear and anxiety disorders, depression, and autism, but it unclear how its circuits form. We will address these questions using cutting-edge tools in systems- and cellular-level Neuroscience and 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 will define the causal function and underlying connectivity of mPFC neurons that contribute to learned fearful behaviors.
mapping the mpfc activity patterns underlying distinct fearful behaviors
Using the UCLA miniscopes, we will explore mPFC activity patterns underlying fearful behaviors including remote memory, extinction, and avoidance, 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.
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
Savas JN, Wang YZ, DeNardo LA, Martinez-Bartolome S, McClatchy DB, Hark TJ, Shanks NF, Cozzolino KA, Lavallée-Adam M, Park SK, Kelly JW, Koo EH, Nakagawa T, Masliah E, Ghosh A, Yates 3rd JR (2017) Amyloid accumulation drives proteome-wide alterations in mouse models of Alzheimer's disease like pathology. Cell Reports 21, 2614-2627.
Allen WE*, DeNardo LA*, Chen MZ*, Liu CD, Loh KM, Fenno LE, Ramakrishnan C, Deisseroth K, Luo L (2017) Thirst-Associated Preoptic Neurons Encode an Aversive Motivational Drive. Science 357, 1149–1155.
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 (2015) The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA receptors. Neuron 87, 764-80.
Wilke SA, Hall BJ, Antonios JK, DeNardo LA, Otto S, Yuan B, Chen F, Tiglio K, Williams ME, Qiu Z, Ghosh A (2012) NeuroD2 Regulates the Development of Hippocampal Mossy Fiber Synapses. Neural Development 7:9.