BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment

Abstract

Sensory, motor, and cognitive stimuli, resulting from interactions with the environment, play a key role in optimizing and modifying the neuronal circuitry required for normal brain function. An experimental animal model for this phenomenon comprises environmental enrichment (EE) in rodents. EE causes profound changes in neuronal and signaling levels of excitation and plasticity throughout the entire central nervous system and the hippocampus is particularly affected. The mechanisms underlying these changes are not yet fully understood. As brain-derived neurotrophic factor (BDNF) supports hippocampal long-term potentiation (LTP), we explored whether it participates in the facilitation of synaptic plasticity and hippocampus-dependent learning that occurs following EE. In the absence of EE, LTP elicited by high-frequency stimulation was equivalent in wildtype mice and heterozygous BDNF 1/2 siblings. LTP elicited by theta-burst stimulation in BDNF 1/2 mice was less than in wildtypes. Long-term depression (LTD) was also impaired. EE for three weeks, beginning after weaning, improved hippocampal LTP in both wildtype and transgenic animals, with LTP in transgenics achieving levels seen in wildtypes in the absence of EE. Object recognition memory was evident in wildtypes 24 h and 7 days after initial object exposure. EE improved memory performance in wildtypes 24 h but not 7 days after initial exposure. BDNF 1/2 mice in the absence of EE showed impaired memory 7 days after initial object exposure that was restored by EE. Western blotting revealed increased levels of BDNF, but not proBDNF, among both EE cohorts. These data support that BDNF plays an intrinsic role in improvements of synaptic plasticity and cognition that occur in EE.

Brain Plasticity and Neurorestoration by Environmental Enrichment

“…Function of BDNF is important in synaptic plasticity [31,32] and previous studies report that its expression is changed following EE [5,33]. 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]. BDNF has been found to play a key role in the late phase of LTP, the best known cellular plasticity occurrence in the brain [36][37][38], which is thought to be one of the plastic occurrence that underlies learning and memory [39][40][41].…”

“…Exposure of rodents to EE is an useful method for increasing both the adult hippocampal neurogenesis [15,51,52] and the survival ratio of new-born neurons in the dentate gyrus [53,54]. Since several studies described that neurogenesis and the survival of new-born neurons are connected to synaptic plasticity and memory function through BDNF/TrkB signaling [55][56][57], it is likely that effects of EE on synaptic plasticity and cognition are enabled by these actions [5].…”

“…Sensory, motor, and cognitive stimulation, interaction by EE are important elements in enhancing and adapting the neuronal system for the normal brain function [5]. Biochemical facilitation and morphological changes can promote functions in animals with brain injury [1,6,7].…”

“…Several studies have shown that, in a brain lesion, brainderived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), or fibroblast growth factor-2 (FGF-2) mediate the neurogenesis and angiogenesis promoting effects of EE [5,7,10,[20][21][22]. These growth factors are essential mediators of the effects of physical activities and EE in brain plasticity [23].…”