Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core.
Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region nucleus accumbens core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stable neuron intrinsic membrane properties. We found that mEPSC frequency is increased in female compared with male MSNs before puberty. Increased mEPSC frequency in female MSNs is abolished after neonatal estradiol or testosterone exposure. MSN intrinsic membrane properties did not differ by sex. These data indicate that neonatal masculinization via estradiol and/or testosterone action is sufficient for down-regulating excitatory synaptic input onto MSNs. We conclude that excitatory synaptic input onto AcbC MSNs is organized long before adulthood via steroid sex hormone action, providing new insight into a mechanism by which sex differences in motivated behavior and other AbcC functions may be generated or compromised.
Department of Biological Sciences (J.C., D.M.D., J.M.), North Carolina State University, Raleigh, North Carolina 27695; W.M. Keck Center for Behavioral Biology (J.C., J.M.), North Carolina State University, Raleigh, North Carolina 27695; Center for Human Health and the Environment (J.M.), North Carolina State University, Raleigh, North Carolina 27695; and Comparative Medicine Institute (J.M.), North Carolina State University, Raleigh, North Carolina 27695.
Jinyan
J
Cao
Department of Biological Sciences (J.C., D.M.D., J.M.), North Carolina State University, Raleigh, North Carolina 27695; W.M. Keck Center for Behavioral Biology (J.C., J.M.), North Carolina State University, Raleigh, North Carolina 27695; Center for Human Health and the Environment (J.M.), North Carolina State University, Raleigh, North Carolina 27695; and Comparative Medicine Institute (J.M.), North Carolina State University, Raleigh, North Carolina 27695.
David M
DM
Dorris
Department of Biological Sciences (J.C., D.M.D., J.M.), North Carolina State University, Raleigh, North Carolina 27695; W.M. Keck Center for Behavioral Biology (J.C., J.M.), North Carolina State University, Raleigh, North Carolina 27695; Center for Human Health and the Environment (J.M.), North Carolina State University, Raleigh, North Carolina 27695; and Comparative Medicine Institute (J.M.), North Carolina State University, Raleigh, North Carolina 27695.
John
J
Meitzen
D000818:Animals; D000831:Animals, Newborn; D004958:Estradiol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005262:Feminization / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D004958:Estradiol