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Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice
Published on: January 20, 2015
Synaptic mechanisms for differential severity of social preference deficits in male and female mice induced by
Kaijie Ma1, Maria Webb2, Samuel S Newton1
1Division of Biomedical and Translational Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
Abstract:
Males are more commonly diagnosed with autism spectrum disorder (ASD) than females with a ratio of about 4-1. However, the neural mechanisms underlying the sex differences in ASD are unknown. Social deficits are the core symptoms of patients with ASD. Previous studies showed that diminished activity-dependent brain-derived neurotrophic factor (BDNF) signaling induced differential severity of autism-like social preference deficits in male and female mice by using a mouse model with genetic knock-in of human BDNF methionine (Met) allele, which significantly decreased activity-dependent BDNF release without affecting basal BDNF secretion. Here, we investigated the synaptic mechanisms for diminished activity-dependent BDNF-induced differential severity of social preference deficits in males and females. The prefrontal cortex (PFC) is a critical brain region for social behaviors. Whole-cell patch-clamp brain slice recordings showed that diminished activity-dependent BDNF signaling differentially increased the frequency of spontaneous action potentials (sAPs) of pyramidal neurons in the PFC of male and female BDNF+/Met mice. The frequency of sAPs in male BDNF+/Met mice was higher than in female BDNF+/Met mice. Diminished activity-dependent BDNF signaling differentially enhanced excitatory synaptic transmission and dampened inhibitory synaptic transmission of pyramidal neurons at pre- and post- synapses in males and females, which were mediated by dysregulated transcriptional levels of key synaptic genes. Chemogenetic inhibition of pyramidal neurons in the PFC of BDNF+/Met mice was sufficient to ameliorate autism-like social preference deficits in males and females. This study reveals synaptic mechanisms underlying the differential severity of social preference deficit in male and female BDNF+/Met mice, which provides a potential neural basis for sex differences in male and female ASD patients with and without the BDNF Val66Met SNP.
