Impaired NMDA Receptor Dependent Long Term Depression in Valproic Acid-Induced Autism Rat Model

• Main Authors: Han-Fang Wu, 吳函芳
• Other Authors: Hui-Ching Lin
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/07529350018832580686

碩士 === 國立陽明大學 === 生理學研究所 === 103 === Autism spectrum disorder (ASD) is classified as neurodevelopmental disorder which is characterized by social interaction impairment, communication impairment and cognitive deficit. Amygdala, in the brain area, is related to socio-emotional behavior and cognition function which are abnormal in ASD. Autism-like phenotypes in valproate (VPA)-exposed offspring has been linked to excitatory/inhibitory (E/I) imbalance and the glutamatergic abnormalities in N-methyl-D-aspartate receptor (NMDAR) are associated with ASD. Additionally, the activation of NMDAR is the major cellular components of long term depression (LTD). However, the regulation of synaptic NMDAR activity within amygdala in ASD remains poorly understood. In this study, we try to characterized the synaptic function and NMDA-dependent LTD of amygdala in the VPA-exposed offspring. The behaviors showed the social ability deficit, anxiety-like behavior and repetitive behavior in VPA-exposed offspring. We utilized the extracellular recording to examine the synaptic function by input-output curve (I-O curve) and paired-pulse facilitation (PPF) on amygdala in VPA-exposed offspring. Theses results showed no significant difference in I-O curve and a siginificant decrease in PPF. We also observed that the low frequency stimulation (LFS)-dependent LTD and NMDA dependent chemical LTD both dysfunction on amygdala in the VPA-exposed offspring. These results suggested the basal neurotransmission do not change but the presynaptic efficiency enhancement. The NMDA receptor may regulates the synaptic plasticity on amygdala which involved in VPA-exposed autism like model and modulation of NMDA receptor offers a potential strategy for ASD treatment.