Physiological effects of enriched environment exposure and LTP induction in the hippocampus in vivo do not transfer faithfully to in vitro slices

A number of experimental paradigms use in vitro brain slices to test for changes in synaptic transmission and plasticity following a behavioral manipulation. For example, a number of previous studies have reported a variety of effects of environmental enrichment (EE) exposure on field potential responses in hippocampal slices, but in no study was is it known what changes had been elicited in vivo. In the present study, we recorded from the hippocampus in vivo while rats underwent a brief period of EE. There was no detectable EE-induced change in synaptic efficacy in the dentate gyrus in vivo, but there was an increase in cellular excitability. In slices prepared from the same animals, we failed to observe any evidence of the excitability increase. We next tested whether LTP induction in vivo was better preserved in vitro. However, when slices from these rats were examined, there was no observable change in perforant path synaptic strength, although there was a modest increase in excitability that correlated with the increased excitability observed in vivo. These findings suggest that synaptic changes induced in vivo either are not preserved faithfully or are difficult to detect in hippocampal slices, while changes in cellular excitability are better preserved.Exposure to an enriched environment (EE) can improve performance on a variety of hippocampus-dependent memory tasks in both normal (Kempermann et al. 1997; Duffy et al. 2001; Teather et al. 2002; Schrijver et al. 2004; Irvine and Abraham 2005) and disease model (Ohlsson and Johansson 1995; Young et al. 1999; Jankowsky et al. 2005; Lazarov et al. 2005; Nithianantharajah and Hannan 2006; Laviola et al. 2008) animals. Previous studies attempting to understand the physiological changes that mediate these effects have yielded mixed results, which may in part be due to the variability in enrichment paradigms used in different laboratories, but which may also be due to the method used to measure hippocampal physiology.Traditionally, researchers have studied the effects of EE using ex vivo brain slices. Such studies have sometimes reported an increase in synaptic strength following enrichment (Green and Greenough 1986; Foster et al. 1996; Foster and Dumas 2001), but a lack of a change has also been observed (Duffy et al. 2001; Feng et al. 2001; Parsley et al. 2007). The ex vivo approach is predicated on the assumption that EE (or other behavioral) treatment induces changes in neural function that are of sufficient magnitude and extent that they will still be present when the brain is removed and studied in vitro. However, there could be many hidden effects of slice preparation (Kirov et al. 2004) that change or obscure effects occurring in vivo.In a previous study, we were surprised to find few effects of a 3-mo EE treatment on hippocampal synaptic function and plasticity when assessed in vitro (Eckert et al. 2010), despite our having observed with in vivo recordings substantial effects with shorter periods of EE exposure (Irvine and Abraham 2005; Irvine et al. 2006). We therefore considered the possibility that effects measured electrophysiologically in vivo may not be readily detectable in vitro. Testing this hypothesis requires studying the same animals in vivo and in vitro, a control procedure we are not aware of having been reported previously in the literature. In the present study, we examined whether the effects of EE or LTP induction in vivo could be detected in hippocampal slices taken from the same animals. We failed to detect any of the in vivo changes, except for a modest increase in cellular excitability following LTP.