8 Hz-induced LTP depends on Ca²⁺ entry during the bursting phase.

<p>The NMDA receptor non-competitive antagonist, MK-801 (0,15 mg/kg i.p.; <i>n</i> = 6) and VGCC blocker Methoxyverapamil (MVP, 100 nmol/5 µl.i.c.v.; <i>n</i> = 6) reduce the plasticity factor (PF) values (A) (student's paired <i>t</i> test, *, <i>p</i><0.05: indicates significance compared to the control group) as well as signal transmission efficacy (ΔSTE) values (B) (student's paired <i>t</i> test,*, <i>p</i><0.05: indicates significance compared to the control group). (C) NMDA and VGCC components in the PF impairment. Upper analog traces: Examples of recording samples show impaired pre-fEPSP current sink and compensatory spiking activity in the MK-801-treated group (middle) compared with the control (left). The right trace reveals reduced polyspikes in the MVP group. Field bursting activity under MK-801 block is increased in comparison to VGCC antagonism (bottom left), and the reduced sum of pre-EPSP current sinks is related to impaired NMDA function (bottom right).</p

LTP correlates with field spiking activity.

<p>(A) fEPSP slope and PS amplitude show initial short-term depression and subsequent long-lasting potentiation after 8 Hz stimulation (ANOVA, <i>p</i><0.001, <i>n</i> = 16). Analog traces represent fEPSPs, prior to and after stimulation, respectively. (B) Correlation between the change in signal transmission efficacy (ΔSTE) and 8 Hz stimulation-related plasticity factor (PF) in a group of naive animals (<i>n</i> = 28). (C) Comparison of PF and ΔSTE between a group of naïve animals that received stimulation, and a group of animals that received re-stimulation after 7 days, indicate a significant decrease of probabilities after re-stimulation (**, <i>p</i><0.01, student's paired <i>t</i> test, <i>n</i> = 6).</p

8 Hz stimulation-induced theta oscillations.

<p>Sample EEG trace from the dentate gyrus representing 8 Hz (30 pulses) stimulation of the medial perforant path and subsequent intrinsic theta oscillations. Arrows indicate the start and the end of the stimulation. The increased theta activity, after the stimulation, is highlighted in the sample trace below. Application of 150–300 Hz band-pass filter reveals ripple oscillations on the positive peak of theta cycle, marked with asterisks (bottom trace).</p

Electrophysiological properties of the dentate gyrus granule cell field response to 8 Hz stimulation.

<p>(A) Sample intrahippocampal electroencephalogram (EEG) demonstrates the appearance of field bursts. Arrows indicate the start and the end of perforant path 8 Hz stimulation; grey arrow shows the appearance of negative shift of DC-potential. Bottom sample trace amplifies the field responses during the bursting phase. Asterisks show the test-pulses that precede each fEPSP bursting response. (B) Sample recordings, from left to right, represent fEPSP traces in controls: early initiation phase, late initiation phase, early bursting phase and late bursting phase, respectively. (C) Summary data show population spike (PS) amplitude and fEPSP slope changes in the course of 8 Hz (144 pulse) stimulation (n = 5). The main phases (initiation, bursting and termination) are divided by vertical lines; the dotted lines indicate the subdivision of the phases (early and late parts). (D) fEPSP parameters involved in the calculation of plasticity factor (PF, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005850#s4" target="_blank">methods</a>) in the time course of 8 Hz stimulation (<i>n</i> = 5). (E) Sample recordings from baseline period and the early and late bursting phases, respectively. The distance between fEPSP initiation and the horizontal line, normalized to the baseline, shows the amplitude of the extracellular pre-EPSP current sink (lower dotted line). The highest value of the fEPSP, normalized to the baseline (upper dotted line), reflects the positive field potential amplitude (PA).</p

Theta oscillation-dependent E-S uncoupling.

<p>(A) Brief 8 Hz (30 pulse) stimulation of the perforant pathway induced, in 43% of all cases, a decrease of the fEPSP slope and an increase of PS amplitude, referred to as EPSP- to-spike uncoupling (E-S uncoupled group, <i>n</i> = 6). (B) A lack of change in fEPSP and PS was observed in the remaining 57% of animals (non E-S uncoupled group, <i>n</i> = 6). (C) An increase of theta spectral power for 18 sec after the stimulation, compared with the EEG epochs of 18 sec prior to the stimulation, was observed in the E-S group only (white squares) (student's paired <i>t</i> test, <i>p</i><0.01, <i>n</i> = 6). The non-E-S group (black squares) did not respond with increased theta. (D) Theta ratio (T-ratio), representing the absolute values of theta range (5–10 Hz) divided by the absolute values of delta range (2–4 Hz), in both groups prior to the stimulation, is shown in the left panel. The right panel demonstrates the difference in the E-S uncoupling ratio (summary values from 4 h of recordings of the ratio between PS amplitude and EPSP slope) from the same animals, (* <i>p</i><0.05).</p

Dissociated test-pulse stimuli and field bursts result in a lack of fEPSP potentiation.

<p>(A) Comparison of the fEPSP slope between animals that experienced an interruption of 8 Hz stimulation prior to the bursting phase, and control animals (that received 144 pulses). Note the immediate difference after the stimulation, during the depression period (ANOVA, <i>p</i><0.01, <i>n</i> = 6). (B) PS amplitude in the same groups. A non-specific significant increase in PS is observed in the non-paired group, when compared to the baseline period values (ANOVA, <i>p</i><0.01, <i>n</i> = 6). (C) Modification of granule cell response after discontinued theta-like stimulation of the medial perforant path, in cases where no generalized field response occurred (<i>n</i> = 5). fEPSP and PS show opposite behaviour - depression and potentiation, respectively. This E-S uncoupling continues for about 24 h.</p

Application of an mGluR1 antagonist prior to, but not after, LFS prevented LTD in the CA1 region

LFS (2 Hz, 1200 pulses) induced persistent LTD which lasted for at least 4 h in the CA1 region . Application of the mGluR1 antagonist LY367285 (100 µ), for 20 min prior to LFS, significantly impaired the induction and expression phases of LTD. Application of the mGluR1 antagonist LY367285 (100 µ) for 20 min after LFS had no effect on the profile of LTD. Bar indicates drug application before (black) or after (grey) LFS. Insets: evoked potentials obtained in the presence of LY387385 applied pre-HFT or LY387385 applied post-HFT at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.<p><b>Copyright information:</b></p><p>Taken from "Metabotropic glutamate receptor 1 (mGluR1) and 5 (mGluR5) regulate late phases of LTP and LTD in the hippocampal CA1 region "</p><p></p><p>The European Journal of Neuroscience 2008;27(6):1345-1352.</p><p>Published online 01 Mar 2008</p><p>PMCID:PMC2327219.</p><p>© The Authors (2008) Journal compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd</p

Application of an mGluR5 antagonist either prior to or after HFT prevented LTP in the CA1 region

(A) HFT (100 Hz) induced persistent LTP (which lasted for at least 4 h) in the CA1 region . Application of the mGluR5 antagonist MPEP (40 µ), for 20 min prior to HFT, significantly prevented both the induction and the expression of LTP. Application of MPEP (40 µ) for 20 min after HFT significantly prevented the expression of LTP beyond 2 h post-HFT. Bar indicates drug application before (black) or after (grey) HFT. (B) Application of MPEP (40 µ) did not affect basal synaptic transmission compared to controls. Bar indicates drug application. Insets: evoked potentials obtained in the presence of vehicle or MPEP (applied pre-HFT) at the timepoints noted: vertical bars, 2 mV; horizontal bars, 2 ms.<p><b>Copyright information:</b></p><p>Taken from "Metabotropic glutamate receptor 1 (mGluR1) and 5 (mGluR5) regulate late phases of LTP and LTD in the hippocampal CA1 region "</p><p></p><p>The European Journal of Neuroscience 2008;27(6):1345-1352.</p><p>Published online 01 Mar 2008</p><p>PMCID:PMC2327219.</p><p>© The Authors (2008) Journal compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd</p

Stimulation-induced theta oscillations throughout 2.5 Hz protocol.

<p>(A) Sample EEG trace, in the time course of 2.5 Hz stimulation, from an animal that did not respond with subsequent fEPSP changes to the stimulation protocol. (B) Sample EEG trace, in the time course of 2.5 Hz stimulation, from an animal that displayed E-S uncoupling after the stimulation protocol. The amplified EEG epoch, demonstrates an occurrence of field patterns of high amplitude in the theta range, from the same EEG record.</p

fEPSP profile depends on the timing of the stimulation-induced theta phase.

<p>(A) Sample EEG trace from a case with stimulation-induced theta oscillations, where positive peaks coincide with entorhinal stimuli (upper trace). The same field potentials represented in ms time scale (bottom traces) show a clear population spike. (B) Sample EEG trace from a case with stimulation-induced theta oscillations, where the positive peaks do not coincide with the entorhinal stimuli (upper trace). The population spike of the same field potentials, measured at ms time scale (bottom traces) is almost absent.</p