Enriched environment and social isolation affect cognition ability via altering excitatory and inhibitory synaptic density in mice hippocampus

Abstract

Background The purpose of the study was to examine whether the underlying mechanism of the alteration of cognitive ability and synaptic plasticity induced by the housing environment is associated with the balance of excitatory/inhibitory synaptic density. Enriched environment (EE) and social isolation (SI) are two different housing environment, and one is to give multiple sensory environments, the other is to give monotonous and lonely environment. Results Male four-week-old C57 mice were divided into three groups: CON, EE and SI. They were housed in the different cage for 3 months. Morris water maze (MWM) and novel object recognition were performed. Long term potentiation (LTP), depotentiation (DEP) and Local field potential (LFPs) were recorded in the hippocampal perforant pathway (PP) and dentate gyrus (DG). The data showed that EE enhanced the ability of spatial learning, reversal learning and memory as well as LTP/DEP in the hippocampal DG region. Meanwhile, SI reduced those abilities and the level of LTP/DEP. Moreover, there were higher couplings of both phase-amplitude and phase-phase in the EE group, and lower couplings of them in the SI group compared to that in the CON group. Western blot analysis showed that EE significantly enhanced the level of PSD-95, NR2B; however, SI reduced them but enhanced level of GABAAR. Conclusion These date suggests that the cognitive functions, synaptic plasticity and neural oscillatory patterns were significantly impacted by housing environment via possibly changing the balance of excitatory and inhibitory synaptic density.

Environmental enrichment mitigates the long-lasting sequelae of perinatal fentanyl exposure

“…Environmental enrichment restored the perinatal fentanyl exposure-induced impairment in LTP in S1 layer 2/3 neurons. This is consistent with findings that environmental enrichment restores stress-induced reduction of LTP in hippocampal dentate gyrus and prefrontal cortical neurons, and that enrichment does not further increase LTP in non-stressed controls (Wang et al, 2020;Wu and Mitra, 2020).…”

“…2H). There was a significant drug × housing interaction (Two-way ANOVA, F (1, 54) = 56.27, p < 10 −4 , Pη 2 = 0.51, large-effect ). Fentanyl-exposed, standard-housed mice continued to respond to the stimuli more than twice as much as vehicle-exposed, standard-housed mice (Tukey’s post hoc, p < 10 −4 , Glass’ delta = 4.31, large-effect ).…”

Associations of Social Isolation and Loneliness With Later Dementia

“…Previous epidemiologic studies have revealed that social isolation is associated with cognitive function in later life, 4 but evidence on the potential mechanism is sparse. Animal studies suggest that isolation affects cognition by altering the excitatory and inhibitory synaptic density in the hippocampus 42 and social interaction reversed the memory deficit by increasing hippocampal neurogenesis. 43 For AD, the largest form of dementia, the neuropathologic changes are suggested to start in the hippocampus and related areas and are associated with early cognitive impairments in learning and memory.…”

Social isolation, loneliness and all-cause dementia: a longitudinal and imaging-genetic study in the UK Biobank cohort

“…Past epidemiological studies have revealed that social isolation was associated with cognitive function in later life, 45 but evidence on the potential mechanism is sparse. Animal studies suggested that isolation affected cognition via altering the excitatory and inhibitory synaptic density in hippocampus, 46 and social interaction rescued memory deficit by increasing hippocampal neurogenesis. 47 The brain reserve hypothesis of dementia posits that larger brains have more neural matter that may increase tolerance of pathology and maintain cognitive function.…”