Long‐lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment

Abstract

Behavioural experience (e.g. chronic stress, environmental enrichment) can have long-lasting effects on cognitive functions. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as hippocampus, we tested whether behaviour has also long-lasting effects on synaptic plasticity by examining the induction of long-term potentiation (LTP) and long-term depression (LTD) in slices of hippocampal CA1 obtained from rats either 7-9 months after social defeat (behavioural stress) or 3-5 weeks after 5-week exposure to environmental enrichment. Compared with age-matched controls, defeated rats showed markedly reduced LTP. LTP was even completely impaired but LTD was enhanced in defeated and, subsequently, individually housed (during the 7-9-month period after defeat) rats. However, increasing stimulus intensity during 100-Hz stimulation resulted in significant LTP. This suggests that the threshold for LTP induction is still raised and that for LTD lowered several months after a short stressful experience. Both LTD and LTP were enhanced in environmentally enriched rats, 3-5 weeks after enrichment, as compared with age-matched controls. Because enrichment reduced paired-pulse facilitation, an increase in presynaptic release, facilitating both LTD and LTP induction, might contribute to enhanced synaptic changes. Consistently, enrichment reduced the number of 100-Hz stimuli required for inducing LTP. But enrichment may also actually enhance the range of synaptic modification. Repeated LTP and LTD induction produced larger synaptic changes in enriched than in control rats. These data reveal that exposure to very different behavioural experiences can produce long-lasting effects on the susceptibility to synaptic plasticity, involving pre- and postsynaptic processes.

Mice Lacking the Immediate Early Gene Egr3 Respond to the Anti-Aggressive Effects of Clozapine Yet are Relatively Resistant to its Sedating Effects

“…We recently found that Egr3À/À mice display a heightened reactivity to stress and abnormalities in their adaptation to novel and stressful stimuli (GallitanoMendel et al, 2007). In addition we found that Egr3À/À mice have deficits in long-term depression (GallitanoMendel et al, 2007), a form of synaptic plasticity triggered by stressful and novel stimuli (Kim et al, 1996;Xu et al, 1997;Manahan-Vaughan and Braunewell, 1999;Braunewell and Manahan-Vaughan, 2001; Artola et al, 2006).…”

Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

“…Environmental enrichment (EE) augments CREB immunoreactivity in the hippocampus (Williams et al 2001;Huang et al 2006Huang et al , 2007, enables LTP reinforcement, increases intrinsic neuronal excitability, and reduces AHP in CA1 neurons (Artola et al 2006;Irvine et al 2006;Kumar and Foster 2007), changes which are also observed in VP16-CREB high mice readily after transgene induction (Barco et al 2002;Lopez de Armentia et al 2007). We speculated that housing in an enriched environment could accentuate the cognitive impairments associated with chronic enhancement of CREB function by further increasing CREB activity.…”

D-Serine Augments NMDA-NR2B Receptor-Dependent Hippocampal Long-Term Depression and Spatial Reversal Learning

“…Changing the location of a hidden platform may be analogous, requiring a refinement or reconfiguration of the previously formed spatial map. Similarly, calcineurin knockout mice show both diminished LTD and poor performance in the delayed-matching-to-sample task (Zeng et al, 2001), while environmental enrichment, the most studied form of cognitive enhancement, increases the propensity for LTP, LTD, and depotentiation/dedepression (Duffy et al, 2001;Abraham et al, 2006;Artola et al, 2006). Modulation of LTD threshold has also been associated with cognitive dysfunction; for example, chronic stress reduces the induction threshold for LTD and leads to cognitive impairments (Xu et al, 1997;Yang et al, 2005).…”