Christine A. Denny

Christine Denny is an American neuroscientist and associate professor of Clinical Neurobiology in Psychiatry in the Department of Psychiatry at Columbia University Irving Medical Center in New York City. Denny investigates the molecular mechanisms underlying learning and memory. She developed a novel technique to label neurons that encode specific memories. She used this technique to probe what happens to hippocampal memory traces in different disease states.

Early life and education Denny grew up in Lyndhurst, New Jersey and attended Lyndhurst High School. While at Boston College, Denny continued to excel in academics as she maintained Honor and Dean's List standing but she also became interested in research and received an Advanced Undergraduate Research Fellowship to support her research. In 2004, Denny began roles as a teaching assistant and laboratory instructor at Boston College. While at Boston College, Denny worked under the mentorship of Thomas N. Seyfried studying lipid storage diseases and metabolic therapies to treat brain diseases. In 2007, Denny published a first author paper in the Journal of Neurochemistry highlighting a model system for assessing retinal pathobiology and therapies for ganglioside storage diseases. Denny also explored lipid abnormalities in mouse models of Rett syndrome as well as the effects of ketogenic diets on alleviating symptoms of Sandhoff disease, a ganglioside storage disease.

Denny then pursued a PhD in neuroscience at Columbia University under the mentorship of Dr. Rene Hen. Denny first explored hippocampal neurogenesis and published a first author paper in 2010 showing that inhibiting neurogenesis increases novel object exploration and impairs one trial contextual fear-learning in mice suggesting an important role for adult born neurons in cognitive function. Denny then began to exploring the idea of memory traces, cells in the brain where memories are stored, and tried to tag these memory traces in the dentate gyrus and CA3 regions of the hippocampus. She was able to develop a genetic tool that enabled her to fluorescently tag neurons that were activated in specific memories. Denny started her own lab at Columbia University in 2013 and began her position as an assistant professor of Clinical Neurobiology in Psychiatry. This technique refined the ability to selectively label memory traces. These findings suggested the possibility of social neural circuits within the infralimbic prefrontal cortex as a therapeutic target for ameliorating anxiety or other disorders of learned fear associations.

Denny's lab also investigates small molecule prophylactics for stress-induced depressive-like behavior. Since psychiatric illnesses often follow stressful events, Denny has proposed the importance of prophylactic therapies in preventing susceptible individuals from developing psychiatric disorders after stressful events. One of the molecules Denny has been exploring the prophylactic therapeutic benefit of is ketamine, a fast acting antidepressant. In a follow-up paper in 2017, Denny and her lab found that administering ketamine right before or right after a fearful event did not protect against fearful events, while administration one week before a stressful event still seemed to provide prophylactic effects and decrease fear responses. After these findings, Denny was interested in looking at the markers of stress resilience following ketamine treatment. In a Nature paper in 2018, Denny found 8 metabolites that were changed in the prefrontal cortex and hippocampus after ketamine administration. One novel finding was that precursors to inhibitory neurotransmitters were increased whereas those for excitatory neurotransmitters were decreased.

Awards and honors NIH Early Independence Award NIH Transformative Award ELabNYC Fellow

Publications Cazzulino AS, Martinez R, Tomm NK, and Denny CA. (2015) Improved specificity of hippocampal memory trace labeling. Hippocampus. Brachman RA, McGowan JC, Perusini JN, Lim SC, Pham TH, Faye C, Gardier AM, Mendez-David I, David DJ, Hen R, and Denny CA. (2015) Ketamine as a prophylactic against stress-induced depressive-like behavior. Biological Psychiatry. (in press). Denny CA, Kheirbek MA, Alba EL, Tanaka KF, Brachman RA, Laughman KB, Tomm NK, Turi GF, Losonczy A, and Hen R. (2014) Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83:189-201. . Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang Y, Srinivas P, Gao X-B, Suyama S, Thomas L, Mann JJ, Horvath T, Bonnin A, and Karsenty G. (2013) Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 26:228-241. . Denny CA, Burghardt NS, Schacter DM, Hen R, and Drew MR. (2012) 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus. 22:1188-1201. . Drew MR, Denny CA, and Hen R. (2010) Arrest of adult hippocampal neurogenesis impairs single- but not multiple-trial contextual fear conditioning. Behav Neurosci. 124:446-454. . Pollak DD, Monje FJ, Zuckerman L, Denny CA, Drew MR, and Kandel ER. (2008) An animal model of a behavioral intervention for depression. Neuron 60, 149–161. .