Social, communication, and cortical structural impairments in Epac2-deficient mice.
Deficits in social and communication behaviors are common features of a number of neurodevelopmental disorders. However, the molecular and cellular substrates of these higher order brain functions are not well understood. Here we report that specific alterations in social and communication behaviors in mice occur as a result of loss of the EPAC2 gene, which encodes a protein kinase A-independent cAMP target. Epac2-deficient mice exhibited robust deficits in social interactions and ultrasonic vocalizations, but displayed normal olfaction, working and reference memory, motor abilities, anxiety, and repetitive behaviors. Epac2-deficient mice displayed abnormal columnar organization in the anterior cingulate cortex, a region implicated in social behavior in humans, but not in somatosensory cortex. In vivo two-photon imaging revealed reduced dendritic spine motility and density on cortical neurons in Epac2-deficient mice, indicating deficits at the synaptic level. Together, these findings provide novel insight into the molecular and cellular substrates of social and communication behavior.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Deepak P
DP
Srivastava
Kelly A
KA
Jones
Kevin M
KM
Woolfrey
Jeffrey
J
Burgdorf
Theron A
TA
Russell
Abigail
A
Kalmbach
Hyerin
H
Lee
Connie
C
Yang
Mazdak M
MM
Bradberry
David
D
Wokosin
Joseph R
JR
Moskal
Manuel F
MF
Casanova
Jack
J
Waters
Peter
P
Penzes
D000818:Animals; D049229:Dendritic Spines / Q000235:genetics* / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics; D008124:Locomotion / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D012919:Social Behavior; D013003:Somatosensory Cortex / Q000166:cytology*; D018709:Statistics, Nonparametric; D014828:Vocalization, Animal / Q000502:physiology*
C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D049452:Green Fluorescent Proteins