Bikbaev and Manahan-Vaughan Figure 2 | A schematic representation of the consequences of high-frequency tetanisation that occur on the network and cellular levels, and lead towards long-term potentiation of synaptic transmission. (A) Strong afferent stimulation results in an enhancement of both theta and gamma oscillations, which occurs within 5 min interval after tetanisation and can be mediated via GABARs, NMDARs and mGluRs. (B) Tetanisation-triggered activation of both ionotropic and metabotropic glutamate recep- tors is followed by the expression of plasticity-related immediate-early genes (IEGs) and protein synthesis, which can underlie structural synaptic reorganisation and long-term increase in synaptic efﬁcacy. Experimental procedures that inhibit the induction, expression or maintenance of LTP can result in impairment of post-tetanic potentiation, STP, early LTP or late LTP (1–4, respec- tively). Grey arrows denote possible links between NMDAR and mGluR activation and facilitation of network activity in theta and gamma frequency bands. by trains of high-frequency stimulation delivered either at the peak or the trough of theta cycle, and which resulted in LTP or LTD respectively (Huerta and Lisman, 1993, 1995; McCartney et al., 2004; Pavlides et al., 1988). During naturally occurring, locomotion-induced theta oscillations, LTP, that persists for at least 48 h, is preferentially induced by stimuli delivered near the local theta peak in behav- ing animals (Hyman et al., 2003; Orr et al., 2001), whereas in anesthetised animals a long-lasting enhancement of fEPSP is elicited, if hippocampal afferents are stimulated synchronously on the peak of theta oscillations (Hölscher et al., 1997; Pavlides et al., 1988). This demonstrates that not only the parameters of the stimulation protocol, but also the timing of tetanisation relative to the phase of theta cycle, can change the direction of synaptic plasticity (LTD vs. LTP). Thus, tetanisation-driven increases of theta and gamma oscillations, such as those observed in our study (Bikbaev and Manahan-Vaughan, 2007), seem to be intrinsically interconnected, and play complementary roles in synaptic potentiation. The heightened theta power in the period after tetani- sation is likely to temporally organise the ﬁring of principal cells within theta time-windows, hence supporting the increase of the amplitude of gamma oscillations. Bearing in mind that the higher ampli- tude of gamma oscillations reﬂects a higher degree of synchronisation in the network (see for review: Axmacher et al., 2006), the increase of gamma power in the period immediately after tetanisation may indicate that, during the facilitated theta activ- ity, the ﬁring of principal cells and interneurons is more synchronised (or precise) and/or recruits more elements into the network activity. Accordingly, enhanced gamma oscillations synchronise neuro- nal ﬁring within narrower gamma time windows and elevate the probability for afferent stimuli to coincide with the peak of theta cycle, where the 60 | July 2008 | Volume 2 | Issue 1 www.frontiersin.org