|Michy P. Kelly, Ph.D.|
|Postdoctoral:||University of Pennsylvania|
|Ph.D.:||Wake Forest University School of Medicine|
Our lab dissects the molecular mechanisms underlying learning and memory and social behaviors. Memories of our social experiences do more than bring us happy thoughts of family and friends, they are necessary for us to learn what is and what is not considered a socially-acceptable behavior. As such, social memories are not only critical to our life-long happiness, they are critical to our health and survival. Unfortunately, a number of neurodevelopmental (e.g., autism), psychiatric (e.g., schizophrenia), and age-related disorders (e.g., age-related cognitive decline) are associated with impairments in social memories and deficits in social behaviors. Our lab explores how alterations in phosphodiesterase and cyclic nucleotide signaling might contribute to impairments in social memories and/or deficits in social interactions and how these signaling pathways might be harnessed to alleviate such suffering. To do this, we couple in vivo behavioral studies with ex vivo biochemical and molecular assays using normal, genetically-modified, and/or pharmacologically-treated rodents. Studies are conducted during adolescence, young adulthood, and late adulthood in order to understand how the molecular mechanisms underlying social memory formation and social interactions may evolve across the lifespan.
Our ultimate hope is that an improved understanding of the molecular mechanisms of social memory formation will lead to the development of novel therapeutics for neurodevelopmental, psychiatric, and/or age-related diseases where social memory formation/retrieval is compromised.
FIGURE: Phosphodiesterase 11A4 (PDE11A4) is the only phosphodiesterase whose expression in brain is restricted to the hippocampal formation (shown here in a sagittal section of a mouse brain). This restricted expression pattern makes PDE11A4 a highly intriguing therapeutic target for neurodevelopmental, psychiatric, and age-related disorders. Consistent with the fact that PDE11A4 is enriched in the ventral hippocampus, a brain region important in the regulation of mood and social behaviors, we have shown that decreasing PDE11A4 alters social interactions and impairs the ability to form social memories. DHIPP—dorsal hippocampus; VHIPP—ventral hippocampus. Figure from Kelly et al., 2015, Current Pharmaceutical Design.
- Pathak G, Agostino MJ, Bishara K, Capell WR, Fisher JL, Hegde S, Ibrahim BA, Pilarzyk K, Sabin C, Tuczkewycz T, Wilson S, and Kelly MP (2016) PDE11A Negatively Regulates Lithium Responsivity. Molecular Psychiatry. Epub ahead of print DOI: MP.2016.155
- Hegde S, Capell WR, Ibrahim BA, Klett J, Patel NS, Sougiannis AT, and Kelly MP (2016) Phosphodiesterase 11A (PDE11A), enriched in ventral hippocampus neurons, is required for the consolidation of social but not non-social memories in mice. Neuropsychopharmacology. 41:2920-2931.
- Hegde S, Hao J, Oliver D, Patel NS, Poupore N, Shtutman M, Kelly MP (2016) PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain. Neuroscience. 335:151-169.
- Pathak G, Ibrahim BA, McCarthy SM, Baker K, and Kelly MP (2015) Amphetamine sensitization in mice is sufficient to produce both manic- and depressive-related behaviors as well as changes in the functional connectivity of corticolimbic structures. Neuropharmacology. 95:434-447.
- Kelly MP (2015) Does Phosphodiesterase 11A (PDE11A) Hold Promise as a Future Therapeutic Target? Current Pharmaceutical Design. 21(3):389-416. [Invited Review].
- Kelly MP, Adamowicz W, Bove S, Hartman AJ, Mariga A, Pathak G, Reinhart V, Romegialli A, and Kleiman RJ (2014) Select 3’,5’-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain. Cellular Signalling. 26:383-397.
- Kelly MP (2014) Putting together the pieces of phosphodiesterase distribution patterns in the brain: A jigsaw puzzle of cyclic nucleotide regulation. Chapter 2 In Brandon NJ & West A, eds. Cyclic Nucleotide Phosphodiesterases in the Central Nervous System: From Biology to Disease. John Wiley & Sons, Inc. [Invited book chapter].
- Kelly MP, Logue SF, Brennan J, Day J, Lakkaraju S, Jiang L, Sukoff Rizzo S, Platt BJ, Dwyer JM, Neal S, Pulito VL, Agostino M, Grauer S, Navarra RL, Kelley C, Comery TA, Murrills RJ, Houslay MD, Brandon NJ (2010) Phosphodiesterase 11A (PDE11A) in brain is enriched in ventral hippocampus and deletion results in psychiatric disease-related phenotypes. PNAS.