Age-dependent Effects of Dopamine on Working Memory and Synaptic Plasticity in Hippocampal CA3-CA1 Synapses in Mice

Abstract

Normal aging in mammals is accompanied by a decline in learning and memory. Dopamine plays a vital role in regulating cognitive functions, but it declines with age: During non-pathological aging, dopamine levels, receptors, and transporters decrease. Regarding the role of the dopaminergic system's changes in old age, we examined the effect of age and applied dopamine on working memory, synaptic transmission, and long-term potentiation (LTP) induction and maintenance in young adult and mature adult mice. We employed the Y-maze spontaneous alteration test to evaluate working memory. Maturation had no observed effect on working memory performance. Interestingly, working memory performance increased following intracerebroventricular administration of dopamine only in mature adult mice. We employed evoked field potential recording (in vitro) to assess the effects of age and maturation on the long-term potentiation (LTP) induction and maintenance. There was no difference in LTP induction and maintenance between young and mature adult mice before dopamine application. However, the application of dopamine on mature adult murine slices increased LTP magnitude compared to slices from young adults. According to the obtained results, it may be concluded that hippocampal neural excitability increased in mature adult subjects, and application of dopamine abolished the difference in neural excitability among young mature and adult mature groups; which was accompanied with increment of working memory and synaptic potentiation in mature adult animals.

Keywords: aging; dopamine; long-term potentiation; synaptic plasticity; working memory.