Sex differences in pre- and post-synaptic glutamate signaling in the nucleus accumbens core

Biology of Sex Differences

Research

Melissa C. Knouse¹  Andre U. Deutschmann¹  Mathieu E. Wimmer¹  Miroslav N. Nenov¹  Lisa A. Briand² 

[1] Department of Psychology, Temple University, Weiss Hall, 1701 North 13th Street, 19122, Philadelphia, PA, USA;Department of Psychology, Temple University, Weiss Hall, 1701 North 13th Street, 19122, Philadelphia, PA, USA;Neuroscience Program, Temple University, Weiss Hall, 1701 North 13th Street, 19122, Philadelphia, PA, USA;

关键词: Nucleus accumbens;    Sex differences;    Glutamate;    PKMζ;    Synaptic plasticity;    Long-term depression;   

DOI  :  10.1186/s13293-023-00537-4

 received in 2023-03-07, accepted in 2023-08-08,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGlutamate signaling within the nucleus accumbens underlies motivated behavior and is involved in psychiatric disease. Although behavioral sex differences in these processes are well-established, the neural mechanisms driving these differences are largely unexplored. In these studies, we examine potential sex differences in synaptic plasticity and excitatory transmission within the nucleus accumbens core. Further understanding of baseline sex differences in reward circuitry will shed light on potential mechanisms driving behavioral differences in motivated behavior and psychiatric disease.MethodsBehaviorally naïve adult male and female Long-Evans rats, C57Bl/6J mice, and constitutive PKMζ knockout mice were killed and tissue containing the nucleus accumbens core was collected for ex vivo slice electrophysiology experiments. Electrophysiology recordings examined baseline sex differences in synaptic plasticity and transmission within this region and the potential role of PKMζ in long-term depression.ResultsWithin the nucleus accumbens core, both female mice and rats exhibit higher AMPA/NMDA ratios compared to male animals. Further, female mice have a larger readily releasable pool of glutamate and lower release probability compared to male mice. No significant sex differences were detected in spontaneous excitatory postsynaptic current amplitude or frequency. Finally, the threshold for induction of long-term depression was lower for male animals than females, an effect that appears to be mediated, in part, by PKMζ.ConclusionsWe conclude that there are baseline sex differences in synaptic plasticity and excitatory transmission in the nucleus accumbens core. Our data suggest there are sex differences at multiple levels in this region that should be considered in the development of pharmacotherapies to treat psychiatric illnesses such as depression and substance use disorder.

【 授权许可】

CC BY   
© Society for Women's Health Research and BioMed Central Ltd. 2023

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