Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2.
Cyclic nucleotide phosphodiesterase 10A (PDE10A) is a member of phosphodiesterase families that degrade cAMP and/or cGMP in distinct intracellular sites. PDE10A has a dual activity on hydrolysis of both cAMP and cGMP, and is prominently expressed in the striatum and the testis. Previous studies suggested that PDE10A is involved in regulation of locomotor activity and potentially related to psychosis, but concrete physiological roles of PDE10A remains elusive yet. In this study, we genetically inactivated PDE10A2, a prominent isoform of PDE10A in the brain, in mice, and demonstrate that PDE10A2 deficiency results in increased social interaction without any major influence on different other behaviors, along with increased levels of striatal cAMP. We also demonstrate that PDE10A2 is selectively distributed in medium spiny neurons, but not interneurons, of the striatal complex. Thus, our results establish a physiological role for PDE10A2 in regulating cAMP pathway and social interaction, and suggest that cAMP signaling cascade in striatal medium spiny neurons might be involved in regulating social interaction behavior in mice.
Sano
Hiromi
H
Molecular Neurogenetics Unit, HMRO, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nagai
Yumiko
Y
Miyakawa
Tsuyoshi
T
Shigemoto
Ryuichi
R
Yokoi
Mineto
M
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D007398:Interpersonal Relations; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D010727:Phosphoric Diester Hydrolases / Q000172:deficiency*; D013550:Swimming
D009419:Nerve Tissue Proteins; D000242:Cyclic AMP; D002795:Choline O-Acetyltransferase; C492284:Pde10a protein, mouse; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP