The Characteristics of LTP Induced in Hippocampal Slices Are Dependent on Slice-Recovery Conditions.

Long-term potentiation (LTP) of synaptic transmission is believed to play an important role in encoding memories in neuronal networks (Bliss and Collingridge 1993; Martin et al. 2000). This phenomenon was first discovered on an in vivo preparation (Bliss and Lomo 1973) but the foremost improvements in deciphering its mechanisms were obtained on the in vitro brain slice preparation (Collingridge et al. 1983; Lynch et al. 1983; Frey et al. 1993; Nguyen et al. 1994; Abel et al. 1997; Giese et al. 1998; Kandel 2001). There are two different techniques to maintain brain slices alive for hours (Dingledine et al. 1980). In the interface-slice preparation, slices are partially submerged in artificial cerebro-spinal fluid (ACSF) with the top surface of the slice exposed to a humidified atmosphere of 95% O2 and 5% CO2. In this case the slice gets oxygen that is diffused through the very thin film of liquid covering the slice. In the submerged-slice preparation, slices are completely submerged in ACSF. In this case, the oxygen supply to the slice is provided by the oxygen dissolved in the ACSF. Researchers use one technique or another depending upon the technical constraints of their experiments. For instance, experiments where imaging measurements are performed using a confocal microscope require the use of the submerged-slice preparation. However, these two different techniques can have different effects on cell physiology. For instance, it was recently found that phosphorylation of alpha calcium/calmodulin-dependent kinase II (αCaMKII) at T286, a phosphorylation playing a key role in LTP (Giese et al. 1998), was transiently increased in slices maintained in submersion but was persistently decreased in slices maintained in interface chambers (Ho et al. 2004). Moreover, there are two different steps in each experiment. After slicing, slices must be left undisturbed (recovery period) for 1.5 h before starting the recordings (recording period). Recovery and recording are not necessarily carried out in the same type of chamber (submersion or interface). For instance, in some studies slices recover in interface and are subsequently tested in a submersion chamber whereas in other experiments recovery and recording are made in submersion. Synaptic plasticity is sensitive not only to the induction stimulus but also to what occurred earlier in the synapse. The fact that synaptic plasticity is dependent on the history of the synapse is known as “metaplasticity” (Abraham and Bear 1996; Abraham and Tate 1997). For instance, inhibition of LTP can be elicited by priming stimulation below threshold for LTP or LTD induction (Christie and Abraham 1992; Huang et al. 1992). Application of the mGluR agonist 1S, 3R-aminocyclopentanedicarboxylic acid (ACPD) leads to a facilitation of LTP induction and persistence, as elicited later by a tetanus normally just above threshold for LTP induction (Cohen and Abraham 1996). It is even possible that a stimulation, which alone has no effect on synaptic plasticity, inhibits the late phase of LTP, a phenomenon called “silent metaplasticity” by Woo and Nguyen (2002). Thus, it could be that the type of chamber used for having the slices recovered (submersion or interface) would influence the characteristics of the LTP subsequently induced in interface conditions. Here we found this to be the case.