Impairment in social interaction and hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in a prenatal valproic acid-induced rat model of autism

چکیده مقاله

It is well established that prenatal valproic acid exposure in rats leads to autism-like behaviours and social deficits. Long-term potentiation changes in the brain have been proposed as a potential mechanism in the development of autistic behaviour. However, there are controversies regarding the effect of in utero valproic acid exposure on long-term potentiation. This study examined the social interaction and long-term potentiation induction in perforant pathway-dentate gyrus synapses in male offspring of a rat model of autism induced by prenatal exposure to valproic acid. On Embryonic Day 12.5, the pregnant dams received an injection of 500 mg/kg valproic acid (intraperitoneal) to produce the autism model. The sociability test was performed between Postnatal Days 37 and 40. The offsprings were urethane-anaesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording on Postnatal Days 45–55. In the dentate gyrus region, excitatory postsynaptic potential slope and population spike amplitude were measured. Valproic acid-exposed offspring showed significantly impaired social interaction. The birth weight in valproic acid-exposed rats was significantly lower than in control rats. The ability of dentate gyrus synapses to induce long-term potentiation was hampered by valproic acid exposure. The decreasing excitatory postsynaptic potential slope and population spike amplitude of long-term potentiation provide evidence in favour of this notion. It is widely supposed that the hippocampus plays a central role in the process of learning and memory as well as social interaction and social memory. Therefore, deficiencies in hippocampal synaptic plasticity may be responsible, at least in part, for the social interaction deficits in valproic acid-exposed rats.