title: PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain.
abstract: Despite the fact that appropriate social behaviors are vital to thriving in one's environment, little is understood of the molecular mechanisms controlling social behaviors or how social experience sculpts these signaling pathways. Here, we determine if Phosphodiesterase 11A (PDE11A), an enzyme that is enriched in the ventral hippocampal formation (VHIPP) and that breaks down cAMP and cGMP, regulates social behaviors. PDE11 wild-type (WT), heterozygous (HT), and knockout (KO) mice were tested in various social approach assays and gene expression differences were measured by RNA sequencing. The effect of social isolation on PDE11A4 compartmentalization and subsequent social interactions and social memory was also assessed. Deletion of PDE11A triggered age- and sex-dependent deficits in social approach in specific social contexts but not others. Mice appear to detect altered social behaviors of PDE11A KO mice, because C57BL/6J mice prefer to spend time with a sex-matched PDE11A WT vs. its KO littermate; whereas, a PDE11A KO prefers to spend time with a novel PDE11A KO vs. its WT littermate. Not only is PDE11A required for intact social interactions, we found that 1month of social isolation vs. group housing decreased PDE11A4 protein expression specifically within the membrane fraction of VHIPP. This isolation-induced decrease in PDE11A4 expression appears functional because social isolation impairs subsequent social approach behavior and social memory in a PDE11A genotype-dependent manner. Pathway analyses following RNA sequencing suggests PDE11A is a key regulator of the oxytocin pathway and membrane signaling, consistent with its pivotal role in regulating social behavior.
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
authors.forename: Shweta
authors.initials: S
authors.lastname: Hegde
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia 29208, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia 29208, United States.
authors.forename: David
authors.initials: D
authors.lastname: Oliver
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
authors.forename: Neema S
authors.initials: NS
authors.lastname: Patel
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poupore
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia 29208, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Shtutman
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
authors.forename: Michy P
authors.initials: MP
authors.lastname: Kelly
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005838:Genotype; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010121:Oxytocin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012919:Social Behavior
chemical_list: D010121:Oxytocin; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C520793:Pde11a protein, mouse
keywords: hippocampus; phosphodiesterase; social approach; social buffering; social memory; social odor recognition