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. 1996 Jul 1;16(13):4293-9.
doi: 10.1523/JNEUROSCI.16-13-04293.1996.

Induction of hebbian and non-hebbian mossy fiber long-term potentiation by distinct patterns of high-frequency stimulation

N N Urban  1 , G Barrionuevo
Affiliations

Induction of hebbian and non-hebbian mossy fiber long-term potentiation by distinct patterns of high-frequency stimulation

N N Urban et al. J Neurosci. .

Abstract

The synapse made by hippocampal mossy fibers onto pyramidal neurons of hippocampal area CA3 displays a form of long-term potentiation (LTP) that is independent of the activation of NMDA receptors. Considerable controversy exists as to whether the induction of mossy fiber LTP requires postsynaptic activation and, thus, whether mossy fiber LTP is Hebbian or non-Hebbian. Here we report the induction of both Hebbian and non-Hebbian forms of long-term potentiation at the mossy fiber-CA3 synapse in in vitro slice preparation. These two forms of potentiation can be induced selectively by different induction conditions. Sustained presynaptic activation is sufficient to induce the non-Hebbian form of mossy fiber LTP, whereas brief presynaptic activation coincident with postsynaptic depolarization is required to induce the Hebbian form. We suggest that non-Hebbian forms of plasticity may play an important role in dynamically regulating the thresholds for inducing Hebbian forms of plasticity.

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Figures

Fig. 1.
Fig. 1.
L-HFS and B-HFS result in different time courses of potentiation. Time of HFS is indicated by the triangle. Each point represents the peak amplitude at the given time point from seven experiments, normalized and averaged. Error bars give the SE. Sample waveforms from before and 15 min after HFS are shown in the inset. A, In seven whole-cell recordings,L-HFS to the mossy fibers resulted in very large PTP lasting for several min after HFS, followed by stable LTP (151 ± 18% of control; n = 7). Scale bar: 100 pA, 10 msec.B, In seven experiments, EPSPs were recorded with intracellular sharp electrodes. B-HFS to the mossy fibers resulted in LTP (169 ± 11% of control; n = 7) without PTP. Scale bar: 10 mV, 20 msec. C, In three experiments, potentiation of the extracellularly recorded field EPSP lasted >2.5 hr after B-HFS. The potentiation at 150 min was 165 ± 20% of control. Scale bar: 0.1 mV, 5 msec.
Fig. 2.
Fig. 2.
Induction of mossy fiber LTP by B-HFS depends on stimulation intensity. A, Mossy fiber field EPSPs were recorded in response to stimulation of the granule cells of the dentate gyrus. B-HFS was applied at the indicated times. Initial responses were recorded by using a stimulation intensity that elicited a response <30% of maximal amplitude. Application of B-HFSat this stimulation intensity did not induce LTP. A second application of B-HFS at a higher intensity resulted in LTP.B, Data from six experiments showing results similar to the experiment in A. Each pair of symbols with aconnecting line represents data from one slice. When applied at a stimulation intensity <30% of maximal, B-HFS failed to induce potentiation (post-B-HFS = 98 ± 7% of control;n = 6). Symbols clustered at the left end of each line indicate the amount of LTP observed at 20 min after this first B-HFS. When the stimulation intensity was increased by the factor indicated on the x-axis, the same B-HFS induced significant LTP (post-B-HFS = 137 ± 9% of control; p < 0.02).
Fig. 3.
Fig. 3.
Induction of mossy fiber LTP by B-HFS requires glutamatergic ionotropic synaptic transmission. A, After recording baseline field EPSPs, 10 mmkynurenic acid (KYN) was applied to block AMPA and NMDA receptors. When evoked EPSPs were eliminated, B-HFS(black diamonds) or L-HFS (opentriangles) was applied, and the KYN was washed out. After L-HFS, the response recovered to a potentiated level (response at 35 min post-HFS = 194 ± 29% of baseline; n = 3), whereas after B-HFS, the response was not potentiated (response at 35 min post-HFS = 92 ± 7% of baseline; n = 15).B, Group data showing recovery from KYN after no HFS (control), B-HFS, andL-HFS were applied during the KYN. Also shown, data from experiments in which LTP was induced after washout of KYN by either B-HFS or L-HFS in the 15 slices in which B-HFS first was applied in the presence of KYN.
Fig. 4.
Fig. 4.
B-HFS does not induce mossy fiber LTP after whole-cell dialysis. A, Averaged data from five experiments in which whole-cell EPSCs (WC EPSC) and field EPSPs (Field EPSP) were recorded simultaneously. At 20 min post-B-HFS, the field EPSP, but not the whole-cell EPSC, was potentiated (EPSP = 162 ± 9%; EPSC = 94 ± 20%;n = 5, p < 0.02). B, EPSC and field EPSP waveforms from one example experiment. Scale bars: 5 msec, 25 pA (EPSC); 2 msec, 0.1 mV (EPSP).
Fig. 5.
Fig. 5.
Induction of mossy fiber LTP by B-HFS requires simultaneous afferent stimulation and postsynaptic depolarization. In six cells, three separate manipulations were tested for their effect on mossy fiber EPSP amplitude. A, B-HFS paired with hyperpolarization (−2.5 nA, 100 msec square pulses passed simultaneously with the application of the B-HFS) failed to induce long-lasting changes in mossy fiber EPSP amplitude (amplitude at 15 min = 91 ± 11% of baseline). B, Depolarization alone (+2.5 nA, 100 msec square pulse repeated 10 times at 5 sec intervals) resulted in a slight decrease in mossy fiber EPSP amplitude (amplitude at 15 min = 81 ± 14% of baseline). C, Pairing of depolarization (+2.5 nA, 100 msec square pulse) with the B-HFS resulted in LTP (amplitude at 15 min = 197 ± 32% of control).
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