The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model

• Published in: PloS one 2013-01, Vol.8 (1), p.e55248
• Main Authors: Lin, Hui-Ching, Gean, Po-Wu, Wang, Chao-Chuan, Chan, Yun-Han, Chen, Po See
• Format: Article
• Language: English
• Subjects: Acids; Amygdala; Amygdala - physiopathology; Analysis of Variance; Animal experimentation; Animals; Anxiety; Autism; Autistic Disorder - chemically induced; Autistic Disorder - metabolism; Behavior; Biology; Brain research; Brain slice preparation; Conditioning, Operant; Emotional behavior; Excitation; Excitatory postsynaptic potentials; Excitatory Postsynaptic Potentials - physiology; Experiments; Fear; Fear - physiology; Glutamic acid receptors (ionotropic); Histological Techniques; Inhibitory Postsynaptic Potentials - physiology; Learning; Long-term potentiation; Long-Term Potentiation - physiology; Medical research; Medicine; Memory; N-Methyl-D-aspartic acid receptors; Neurons; Offspring; Patch-Clamp Techniques; Pyramidal cells; Rats; Rats, Sprague-Dawley; Rodents; Social Behavior; Social networks; Studies; Synapses - physiology; Synaptic transmission; Thalamus; Valproic acid; Valproic Acid - toxicity; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055248

The amygdala is an important structure contributing to socio-emotional behavior. However, the role of the amygdala in autism remains inconclusive. In this study, we used the 28-35 days valproate (VPA)-induced rat model of autism to observe the autistic phenotypes and evaluate their synaptic characteristics in the lateral nucleus (LA) of the amygdala. The VPA-treated offspring demonstrated less social interaction, increased anxiety, enhanced fear learning and impaired fear memory extinction. Slice preparation and electrophysiological recordings of the amygdala showed significantly enhanced long-term potentiation (LTP) while stimulating the thalamic-amygdala pathway of the LA. In addition, the pair pulse facilitation (PPF) at 30- and 60-ms intervals decreased significantly. Whole-cell recordings of the LA pyramidal neurons showed an increased miniature excitatory postsynaptic current (EPSC) frequency and amplitude. The relative contributions of the AMPA receptor and NMDA receptor to the EPSCs did not differ significantly between groups. These results suggested that the enhancement of the presynaptic efficiency of excitatory synaptic transmission might be associated with hyperexcitibility and enhanced LTP in LA pyramidal neurons. Disruption of the synaptic excitatory/inhibitory (E/I) balance in the LA of VPA-treated rats might play certain roles in the development of behaviors in the rat that may be relevant to autism. Further experiments to demonstrate the direct link are warranted.