Enhanced synaptic properties of the prefrontal cortex and hippocampus after learning a spatial working memory task in adult male mice

Abstract

Development of novel pharmaceutical compounds for neuropsychiatric disorders, and particularly for the cognitive symptoms of these disorders, is a significantly slow and expensive process. Alternate therapeutic regimens include cognitive training, a particular form of which is working memory training (WMT). WMT has been suggested to improve several cognitive functions, although the results in the scientific literature are conflicting.However, we still do not understand the neurobiological basis that could explain the beneficial effects of WMT. In our study, we investigated the effects of WMT on reference memory, reversal learning and synaptic plasticity in mice. Specifically, male mice were trained in the delayed alternation task for 9 days and were subsequently tested for retention of left-right discrimination memory and reversal learning. Besides the group that underwent WMT, two control groups were included: an active control group that underwent the alternation procedure in the T-maze but without any delays (non-adaptive) and a passive group that remained in their home cage (naive). The adaptive WMT group performed significantly better in the reversal-learning task compared to both non-adaptive and naïve groups and in the left-right discrimination recall compared to the non-adaptive group only.Electrophysiological recordings in brain slices from the same cohort, 2-3 days following behavioral testing, showed that the adaptive WMT enhanced long-term potentiation (LTP) in the prefrontal cortex (PFC), compared to the non-adaptive or the naive groups. In the hippocampus (HPC), both the adaptive and non-adaptive groups exhibited increased synaptic response to current stimulation compared to the naïve group, but no differences were found in LTP. Our results indicate that WMT affects both behavior and underlying neurophysiological properties, suggesting that this type of training could have beneficial effects in both PFC and hippocampal function.

Examining Adolescence as a Sensitive Period for High-Fat, High-Sugar Diet Exposure: A Systematic Review of the Animal Literature

“…Additional research is needed to better understand potential long-term effects of adolescent consumption of fat and sugar on risk for cognitive decline in late life as well as to identify effective approaches prevention and intervention. One candidate for study may be working memory training as this has been shown to improve reference memory, reversal learning, and synaptic plasticity in rodents (Ioakeimidis et al, 2018).…”