Short-term environmental enrichment enhances synaptic plasticity in hippocampal slices from aged rats

Abstract

Age-associated changes in cognition are mirrored by impairments in cellular models of memory and learning, such as long-term potentiation (LTP) and long-term depression (LTD). In young rodents, environmental enrichment (EE) can enhance memory, alter LTP and LTD, as well as reverse cognitive deficits induced by aging. Whether short-term EE can benefit cognition and synaptic plasticity in aged rodents is unclear. Here, we tested if short-term EE could overcome age-associated impairments in induction of LTP and LTD. LTP and LTD could not be induced in the CA1 region of hippocampal slices in control, aged rats using standard stimuli that are highly effective in young rats. However, exposure of aged littermates to EE for three weeks enabled successful induction of LTP and LTD. EE-facilitated LTP was dependent upon N-methyl-D-aspartate receptors (NMDARs). These alterations in synaptic plasticity occurred with elevated levels of phosphorylated cAMP response element-binding protein and vascular endothelial growth factor, but in the absence of changes in several other synaptic and cellular markers. Importantly, our study suggests that even a relatively short period of EE is sufficient to alter synaptic plasticity and molecular markers linked to cognitive function in aged animals.

Brain Plasticity and Neurorestoration by Environmental Enrichment

“…VEGF encourages hippocampus-dependent memory independently of its effects on neurogenesis and angiogenesis, by increasing the synaptic strength [68,69]. Recent studies have been reported that short-term exposure to EE is also enough to alter synaptic plasticity and molecular markers related to the cognitive function [4]. EE-facilitated LTP was dependent upon NMDA receptors.…”

“…Physical exercise exposure has been shown to increase object recognition memory and to encourage BDNF expression in rats [30,34], and the relations of EE and exercise on sensory gating and spatial memory has been formerly reported in rodents [30,35]. In rodents, EE can improve memory and long-term potentiation (LTP) [4]. Another study described that BDNF is increased following EE, and this EE-induced BDNF goes with the enhancement of the object recognition memory and the improvement of LTP [5].…”

“…EE-facilitated LTP was dependent upon NMDA receptors. These changes in synaptic plasticity occurred with raised levels of phosphorylated cAMP response element-binding protein (CREB) and VEGF [4].…”

“…EE is designed for enhancing social interactions, sensory and motor stimulation and learning and memory in a larger cage than standard cage, and this cage contains a variety of toys such as tunnels, platforms, and running wheels [3,4] (Fig. 1).…”

Enriching hippocampal memory function in older adults through video games

“…Despite the simplicity of this manipulation, environmental enrichment has been repeatedly shown to provide numerous structural and functional benefits to the hippocampus (Clemenson, Gage, & Stark, 2018). Importantly, environmental enrichment has been shown to improve both structural and cognitive deficits associated with aging, such as increased neurogenesis (Kempermann, Gast, & Gage, 2002;Leal-Galicia, Castañeda-Bueno, Quiroz-Baez, & Arias, 2008;Segovia, Yagüe, García-Verdugo, & Mora, 2006;Speisman et al, 2013), dendritic branching and spine density (Darmopil, Petanjek, Mohammed, & Bogdanović, 2009), expression of presynaptic proteins (Frick & Fernandez, 2003;Leal-Galicia et al, 2008;Saito et al, 1994), neurotransmitter release (Segovia et al, 2006), enhanced long-term potentiation and depression (Kumar, Rani, Tchigranova, Lee, & Foster, 2012;Stein, O'Dell, Funatsu, Zorumski, & Izumi, 2016), and related hippocampus-dependent behaviors (Kempermann et al, 2002;Segovia et al, 2006;Speisman et al, 2013). Whether the benefits of environmental enrichment are due to physical activity (Kobilo et al, 2011;Mustroph et al, 2012;van Praag, Kempermann, & Gage, 1999), spatial exploration (Freund et al, 2013), learning (Gould, Beylin, Tanapat, Reeves, & Shors, 1999;Leuner et al, 2004), or other aspects of the environment (Birch, McGarry, & Kelly, 2013;Steiner, Zurborg, Hörster, Fabel, & Kempermann, 2008), the surrounding environment can have a significant impact on the aging hippocampus of animals.…”