Christine Ann Denny, PhD
Research Interest
Overview of Research
My laboratory is interested in the molecular mechanisms underlying learning and memory. We have developed a novel technique to label the cells that encode individual memories in the brains of mice. We are then able to indelibly tag these neurons using fluorescent molecules. Using these mice, we have shown how a number of conditions affect memory traces in the hippocampus, specifically in the dentate gyrus and CA3 subregions. Moreover, we have been able to optogenetically inhibit these cells and show their necessity for memory expression.
Currently, we are using these mice to investigate what happens to hippocampal memory traces in stressed, depressed, aged, or Alzheimer’s diseased mice. By combining this unique murine line with disease models and optogenetic reporter lines, we hope to identify the altered memory circuits in these conditions and how to manipulate them in order to improve memory abnormalities. We hope that these studies may halt, or even reverse, the process of Alzheimer's disease-related memory loss or cognitive aging.
In a second line of research, we are also developing novel compounds as prophylactics against stress. We initially began our prophylactic work on ketamine, which has been shown to have rapid-acting and long-lasting effects in rodents and humans following stressful situations. We have identified a number of conditions in which ketamine improves behavior and are interested in identifying the molecular mechanisms by which ketamine improves mood. Current studies are aimed at utilizing developing novel compounds as prophylactics.
• BS, 2005 Biology, Boston College
• MS, 2006 Biology, Boston College
• PhD, 2012 Biological Sciences, Columbia University - New York
Amgen Scholars Summer Research Program
Molecular and Cellular Cognition Society (MCCS)
Society for Neuroscience (SfN)
National Institutes of Health (NIH), Early Independence Award, DP5-OD017908-01, 2013-2018
Optogenetic dissection of hippocampal circuitry underlying Alzheimer’s disease.
New York Stem Cell Science (NYSTEM), Shared Facilities , N13S-006, 2014-2018
Imaging stem cells in the brain for studying neuropsychiatric disorders.
Brain & Behavior Research Foundation (BBRF), NARSAD Young Investigator Award, 2015-2017
Utilizing a novel transgenic mouse line and ketamine to investigate the pathophysiology and treatment of depression.
- Alessia Mastrodonato, Post-doctoral fellow
- Holly Hunsberger, Post-doctoral fellow
- Sofia Leal Santos, MD/PhD Student
- Marcos Lanio, MD/PhD Student
- Michelle Jin, rotating MD/PhD Student
- Josephine McGowan, NB&B PhD Student
- Briana Chen, NB&B PhD Student
- Michelle Stackmann, NB&B PhD Student
- Nick Bulthuis, NB&B PhD Student
- Allegra DeLandri, Lab Manager
1. Chen BK, Luna VM, Shannon ME, Hunsberger HC, Mastrodonato A, Stackmann M, McGowan JC, Rubinstenn G, and Denny CA*. (2021) Fluoroethylnormemantine, a novel NMDA receptor antagonist for the prevention and treatment of stress-induced maladaptive behavior. Biol Psychiatry. in press.
2. Leal Santos S, Stackmann M, Muñoz Zamora A, Mastrodonato A, De Landri AV, Vaughan N, Chen BK, Lanio M, and Denny CA. (2021). Propranolol decreases fear expression by modulating fear memory traces. Biol Psychiatry. In press. PMID: 33766406.
3. Lacagnina AF, Brockway ET, Crovetti CR, Shue F, McCarty MJ, Sattler KP, Lim SC, Santos SL, Denny CA, and Drew MR. (2019) Identification and manipulation of a hippocampal fear extinction engram. Nat Neurosci. 22:753-761. PMID: 30936555.
4. Mastrodonato A, Martinez R, Pavlova IP, LaGamma CT, Brachman RA, Robison AJ, and Denny CA*. (2018) Ventral CA3 deltaFosB expression mediates prophylactic ketamine efficacy against stress-induced depressive-like behavior. Biol Psychiatry. 84: 846-856. PMID: 29615190.
5. Sun Q, Sotayo A, Cazzulino AS, Snyder AM, Denny CA, and Siegelbaum SS. (2017) Proximodistal heterogeneity of hippocampal CA3 pyramidal neuron intrinsic properties, connectivity and reactivation during memory recall. Neuron. 95: 656-672. PMID: 28772124.
6. Brachman RA, McGowan JC, Perusini JN, Lim SC, Pham TH, Faye C, Gardier AM, Mendez-David I, David DJ, Hen R, and Denny CA*. (2016) Ketamine as a prophylactic against stress-induced depressive-like behavior. Biol Psychiatry. 79: 776-786. PMID: 26037911.
7. Root CM, Denny CA, Hen R, and Axel R. (2014) The participation of cortical amygdala in innate, odor-driven behavior. Nature 515: 269-273. PMID: 25383519.
8. 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. PMID: 24991962.
For a complete list of publications, please see
https://www.ncbi.nlm.nih.gov/myncbi/1Xkma8kVtoukb/bibliography/public/
- Neurobiology of Disease
- Neurobiology of Learning and Memory
- Stem Cell Biology