Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus

Abstract

We examined synaptic plasticity in the dentate gyrus (DG) of the hippocampus in vitro in juvenile C57Bl6 mice (28-40 days of age), housed in control conditions with minimal enrichment (Controls) or with access to an exercise wheel (Runners). LTP expression was significantly greater in slices from Runners than in those from Controls, but could be blocked by APV in both groups. LTP was significantly reduced by NR2B subunit antagonists in both groups. NVP-AAM077, an antagonist with a higher preference for NR2A subunits over NR2B subunits, blocked LTP in slices from Runners and produced a slight depression in Control animals. LTD in the DG was also blocked by APV, but not by either of the NR2B specific antagonists. Strikingly, NVP-AAM077 prevented LTD in Runners, but not in Control animals, suggesting an increased involvement of NR2A subunits in LTD in animals that exercise. NVP-AAM077 did not block LTD in NR2A Knock Out (KO) animals that exercised, as expected. In an attempt to discern whether NMDA receptors located at extrasynaptic sites could play a role in the induction of LTD, DL-TBOA was used to block excitatory amino acid transport and increase extracellular glutamate levels. Under these conditions, LTD was not blocked by the co-application of a specific NR2B subunit antagonist in either group, but NVP-AAM077 again blocked LTD selectively in Runners. These results indicate that NR2A and NR2B subunits play a significant role in LTP in the DG, and that exercise can significantly alter the contribution of NMDA NR2A subunits to LTD.

A bout of voluntary running enhances context conditioned fear, its extinction, and its reconsolidation

“…NMDA-dependent cellular mechanisms could also mediate the effects of running on consolidation of the fear memory, its extinction, and its reconsolidation. Consistent with this suggestion, exercise altered the contribution of NMDA NR2A subunits to synaptic plasticity in the dentate gyrus (Vasuta et al 2007). Administration of the NMDA receptor antagonist MK-801 was shown to reduce both the arterial pressure and heart rate increase evoked by dynamic exercise (Camargo et al 2013).…”

“…Extinction learning involves a distributed network of brain areas centered around activity in the BLA, while consolidation recruits other circuits and brain areas (Herry et al 2010). Memory consolidation, extinction, and reconsolidation have been shown to be dependent on activation of glutamate NMDA receptors, and physical exercise may act to augment these mechanisms (Vasuta et al 2007). NMDA receptor antagonists have been demonstrated to disrupt the consolidation (Goeldner et al 2009;Charlier and Tirelli 2011), extinction (Falls et al 1992 (Lee et al 2006;Kalisch et al 2009;Yamada et al 2009) and facilitate extinction (Walker et al 2002;Ledgerwood et al 2003;Vervliet 2008).…”

Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation

“…Previous studies support the enhancement effects of exercise on LTP only at the dentate gyrus (DG) but not the CA1 synapses in wild-type animals with normal health conditions (van Praag et al 1999;Vasuta et al 2007). However, physical training can revert the reduced CA1 LTP in rodents following disturbance such as epilepsy or sleep deprivation (Arida et al 2004;Zagaar et al 2013).…”

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

“…The glutamate receptor, NMDA, is involved in activity-dependent synaptic plasticity, including long-term potentiation (41). It was identified that exercise is a necessary step for initiating activity of the NMDA receptor in the hippocampus (42) and that exercise-enhanced NMDA receptor expression promotes postnatal motor-unit maturation in a spinal muscular atrophy mouse model (43).…”