| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RAPID COMMUNICATION
Laboratoire de Neurobiologie de l'Apprentissage et de la Mémoire, Centre National de la Recherche Scientifique URA 1491, Université Paris Sud, 91405 Orsay, France
 |
ABSTRACT |
|---|
 Abstract
 Introduction
Methods
Results
Discussion
References
|
|---|
Burette, F., T. M. Jay, and S. Laroche. Reversal of LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo with low-frequency patterns of stimulation that do not produce LTD. J. Neurophysiol. 78: 1155-1160, 1997. We examined the efficacy of several patterns of low-frequency stimulation for producing long-term depression (LTD) or depotentiation in the hippocampal fiber pathway to the prefrontal cortex in the anesthetized rat. Field potentials elicited by stimulation of the CA1/subicular region of the ventral hippocampus were recorded in the prelimbic area of the prefrontal cortex. We found no evidence that low-frequency trains (0.5-1 Hz), consisting of either single pulses, paired pulses (35-ms interpulse interval), or two-pulse bursts (5-ms interval), produce LTD in the prefrontal cortex. In contrast, all three stimulus protocols were found to induce a small-amplitude, persistent potentiation of the amplitude of the negative wave of the field response recorded in the prefrontal cortex. We also examined the ability of patterns of low-frequency stimulation to produce depotentiation of previously established long-term potentiation (LTP). Although low-frequency stimulation with single pulses or paired pulses was ineffective, we found that the two-pulse burst protocol selectively produced a rapid reversal of LTP in the hippocampo-prefrontal cortex pathway. Depotentiation is reversible and can be induced >2 h after the induction of LTP. Repeated trains failed to decrease the prefrontal cortex response below the original, unpotentiated level. These findings demonstrate the existence of a depotentiation mechanism that is capable of exerting powerful control over ongoing or recently induced synaptic plasticity in hippocampocortical connections in vivo.
Electrophysiological and anatomic studies have shown a direct monosynaptic projection that originates in the CA1/subicular region and projects to medial orbital and prelimbic areas of the prefrontal cortex (PFC) (Jay and Witter 1991 Adult male Sprague-Dawley rats (n = 36), weighing 300-400 g, were anesthetized with pentobarbitone sodium (65 mg/kg ip, supplemented if necessary during surgery) and placed in a stereotaxic frame. Body temperature was maintained at 37°C. The procedures for implantation and recording extracellular field potentials in the prelimbic area of the PFC are described elsewhere (Laroche et al. 1990 Failure to induce LTD or depotentiation with single- or paired-pulse low-frequency trains
The effect of low-frequency stimulation on synaptic transmission in naive (unpotentiated) hippocampal PFC synapses was investigated in nine rats. After a 30-min baseline, stimulation at 1 Hz was delivered for 15 min. The amplitude of the response decreased during the 1-Hz train (
Induction of depotentiation, but not LTD, with TPB low-frequency stimulation
Nine rats were used in this experiment. After a 30-min baseline recording period, the TPB low-frequency train was delivered (900 bursts at 1 Hz, 5-ms interpulse interval), followed by a 60-min recording period at test frequency and the induction of LTP. Each pair in the train evoked a single response in the prelimbic area of the PFC (Fig. 2Ba), which increased transiently during the early phase of the TPB train to return progressively toward baseline during the later phase (Fig. 2A). Again, a slow-onset but persistent potentiation of the response followed [10.8 ± 3.5%; F(1,8) = 9.4;P < 0.05; Fig. 2A], and two successive episodes of high-frequency stimulation resulted in a further potentiation of the response [50.3 ± 5.5%, compared with the values obtained after the TPB train; F(1,8) = 46.0; P < 0.0001].
These experiments demonstrate, first, that low-frequency stimulus protocols that have been reported to elicit LTD or depotentiation in specific hippocampal and neocortical pathways under certain circumstances are not effective in inducing LTD in the hippocampal fiber system to the PFC in vivo. Prolonged low-frequency stimulation (1-5 Hz) has been shown to induce LTD in CA1 (Dudek and Bear 1992
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
). This pathway uses glutamate as a transmitter (Jay et al. 1992) and is of particular importance because it connects two structures critical for memory function. We have previously shown that high-frequency stimulation of the hippocampus induces long-term potentiation (LTP) of stimulated synapses in the PFC in vivo (Laroche et al. 1990), and that LTP is prevented by blockade of the N-methyl-D-aspartate (NMDA) receptor (Jay et al. 1995). Although LTP in neural networks is accepted widely as a potential candidate for the cellular storage of information, it is also predicted the networks have the capacity to undergo a form of long-term depression (LTD) or depotentiation of previously potentiated synapses, and the question arises as to whether this pathway supports LTD. There is in fact experimental evidence to suggest that both synaptic potentiation and synaptic depression occur in hippocampo-PFC synapses during certain behavioral training conditions (Doyère et al. 1993), yet the type of neuronal activation required to produce LTD or depotentiation in this pathway remains undetermined. In the hippocampus, different patterns of synaptic activation can induce LTD or depotentiation in certain pathways and experimental conditions. For example, one form of LTD that has been widely studied in area CA1 is induced by delivery of prolonged low-frequency stimulation, typically at 1-5 Hz, in hippocampal slices from young animals (Dudek and Bear 1992; Mulkey and Malenka 1992). The efficacy of this protocol in inducing LTD in the adult rat in vivo (Heynen et al. 1996) remains controversial, however, because several studies have reported mainly depotentiation (Barrionuevo et al. 1980; Stäubli and Lynch 1990) or no effect (Errington et al. 1995). More recently, a stimulation pattern consisting of pairs of pulses at low frequency was shown to reliably induce LTD in area CA1 of the adult rat in vivo (Doyère et al. 1996; Thiels et al. 1994), and although this protocol appears ineffective in the dentate gyrus (Doyère et al. 1996), LTD in this region has been obtained with the use of pairs of two pulses at very short intervals (Thiels et al. 1996). In the neocortex, LTD has also been mostly studied with the use of the in vitro slice preparation (Artola et al. 1990; Bindman et al. 1988), including slices of the PFC (Hirsch and Crépel 1990). Although recent experiments have shown that low-frequency trains similar to those used in the hippocampal slice can produce LTD in cortical slices (Dudek and Friedlander 1996; Kirkwood et al. 1993), it is as yet uncertain to what extent this can be applied to synaptic plasticity in the neocortex in vivo. In view of the potential importance of hippocampocortical communication in memory processes and of mechanisms of downregulation of synaptic efficacy for the efficient storage of information, we examined the ability of several patterns of low-frequency stimulation to induce LTD and depotentiation in the hippocampo-PFC pathway in vivo.
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). Briefly, recording electrodes (62-µm nichrome wire) were positioned in the prelimbic cortex (coordinates: 3.2 mm anterior to bregma, 0.8 mm lateral to the midline) and a concentric bipolar stainless steel stimulating electrode was lowered ipsilaterally into the CA1/subicular region of the ventral hippocampus (coordinates: 6.4 mm posterior to bregma, 5.6 mm lateral to the midline). Stimulations of the CA1/subicular region evoked a characteristic monosynaptic negativegoing field potential with a peak latency of 18-21 ms. The depths of the recording and stimulating electrodes (
3.2 and 5.5 mm below the cortical surface, respectively) were adjusted to maximize the amplitude of the negativegoing field excitatory postsynaptic potential. Test pulses (120-200 µs) were delivered every 30 s via an isolated constant current unit at an intensity that evoked a response of 70% of its maximum (range: 150-500 µA). At this intensity, the field potential is most likely to reflect summated excitatory postsynaptic potentials(Laroche et al. 1990). High-frequency stimulation to induce LTP consisted of two series of 10 trains (250 Hz, 200 ms) at 0.1 Hz, 6 min apart, delivered at test intensity. Protocols for inducing LTD consisted of 1) 900 pulses at 1 Hz, 2) 450 pairs of pulses delivered at 0.5 Hz, with an interpulse interval of 35 ms (paired pulse), and 3) 900 bursts of 2 pulses, at 1 Hz, with 5 ms between pulses in a burst [2-pulse burst (TPB)]. The intensity was the same as that of the test pulse. Field potentials were amplified, filtered (band pass 0.1 Hz to 3 kHz), digitized at 20 kHz, and stored on disc as averages of four consecutive responses. The amplitude of the negativegoing component of the field potential was measured by dropping a line from a tangent drawn between the negative peak onset and offset and was analyzed off-line with the use of theA/Dvance software (Mckellar Design). Results were expressed for each animal as a percentage change of the baseline and analyzed by analysis of variance. Correct placement of the electrodes was verified post mortem on brain sections stained with cresyl violet.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
22.6 ± 4.3%, mean ± SE), recovering to baseline within 5 min after resumption of test frequency stimulation (Fig. 1A). There was no evidence of LTD during the post-1-Hz stimulation period. In contrast, a small but significant increase in the response occurred within 10 min after 1-Hz stimulation (Fig. 1, A and B). Values 30-60 min after 1-Hz stimulation were significantly above baseline [11.9 ± 3.8%; F(1,8) = 8.63;P < 0.05]. Thus low-frequency (1-Hz) stimulation induces a form of slow-onset, persistent potentiation in the hippocampo-PFC pathway. High-frequency stimulation delivered 60 min after 1-Hz stimulation resulted in a further increase in the response [30.7 ± 7.5%, compared with pretetanus values; F(1,8) = 16.8; P < 0.005]. No additional LTP was observed after the second tetanus, delivered 30 min later.
View larger version (26K):
[in a new window]
FIG. 1.
Low-frequency single- or paired-pulse stimulation does not produce long-term depression (LTD) or depotentiation in hippocampoprefrontal cortex pathway of anesthetized rat. A: effect of 1-Hz stimulation (900 pulses, thick horizontal bar) on amplitude of postsynaptic potential evoked in prefrontal cortex (PFC) by stimulation of CA1/subiculum (n = 9). Each point in this and subsequent graphs represents group mean ± SE of averaged response to 4 test stimuli given at 30-s intervals. Values are expressed as % change relative to baseline. Stimulation at 1 Hz induced slow-onset potentiation, rather than LTD, and high-frequency stimulation ( 
) delivered 60 min later induced long-term potentiation (LTP). Ba-Bc: examples of averaged responses recorded in PFC at times indicated by letters in A (calibration: 0.1 mV, 20 ms). C: low-frequency (0.5-Hz) paired-pulse stimulation (450 pairs, 35-ms interpulse interval, hatched horizontal bar) also induced potentiation of response (n = 9). Sample responses collected during paired-pulse train are shown in Bd. D: paired-pulse stimulation (hatched horizontal bar) and 1-Hz single-pulse stimulation (thick horizontal bar) given after induction of LTP (n = 8) produced transient depression of PFC response, but depotentiation was not observed.
26.4 ± 6.5%; Fig. 1Bd). This procedure, however, failed to induce LTD (Fig. 1C). There was a decrease in the amplitude of the response during the paired-pulse train (13.0 ± 2.2%), but again, as in the preceding experiment, the response recovered rapidly and potentiation of the response occurred [10.4 ± 3.6%; F(1,8) = 8.4; P < 0,05; Fig. 1C]. Thirty to 60 min after the paired-pulse train, the amplitude of the response was still significantly above baseline [F(1,8) = 10.8; P < 0.05], and high-frequency stimulation resulted in a further potentiation of the response[30.9 ± 6.0%, compared with values after the paired-pulse train; F(1,8) = 26.3; P < 0.001; Fig. 1C]. The second tetanus, delivered 30 min later, produced no further LTP.
29.8 ± 3.8% and 32.1 ± 3.8%, respectively), but in each case there was rapid recovery and the values 10-30 min after the end of the low-frequency trains were not significantly different from the potentiated level observed 30-60 min after the tetanus. During paired-pulse stimulation, a decrease in the response to the second pulse of the pair was observed in all animals (46.8 ± 5.5%).
View larger version (26K):
[in a new window]
FIG. 2.
Two-pulse burst (TPB) low-frequency stimulation induces depotentiation, but not LTD, in hippocampo-PFC pathway of anesthetized rat. A: effect of TPB stimulation (900 bursts at 1 Hz, 5 ms between pulses in burst, open horizontal bar) on amplitude of postsynaptic potential evoked in PFC by stimulation of hippocampus (n = 9). TPB stimulation induced slow-onset potentiation, rather than LTD, and high-frequency stimulation ( ) delivered 60 min later induced LTP. Ba: example of response observed during TPB (calibration as in Fig. 1B). C: LTP was 1st induced with 2 episodes of tetanic stimulation (). Sixty min later, TPB stimulation (open horizontal bar) induced depotentiation of PFC response (n = 9). This was followed by slow-onset potentiation (see also Fig. 2A), and tetanus given 1 h later reinduced LTP. Sample responses collected at times indicated by letters are shown in Bb-Be. D: 3 successive TPB trains at 60-min intervals (open horizontal bars), given 136 min after LTP induction (n = 5), induced depotentiation, but failed to decrease PFC response below original, unpotentiated level.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
; Mulkey and Malenka 1992) and in the visual cortex (Kirkwood et al. 1993) in in vitro slice preparations. In the hippocampus, the efficacy of this protocol in inducing LTD in the adult rat in vitro or in vivo has been met with mixed success. For example, Heynen et al. (1996) have shown induction of LTD with these parameters, whereas others reported either depotentiation (Fujii et al. 1991; O'Dell and Kandel 1994; Stäubli and Lynch 1990) or no effect (Errington et al. 1995). In the PFC in vivo, our results show that a similar prolonged low-frequency (1-Hz) stimulation induces potentiation rather than depression. Another stimulation pattern, low-frequency pairs of pulses, which has been previously shown to produce LTD in area CA1 in the adult anesthetized (Thiels et al. 1994) and freely moving rat (Doyère et al. 1996), also failed to induce LTD in the PFC. In contrast, we repeatedly found that these low-frequency stimulation patterns induced a small amount of potentiation in this pathway, and a similar effect was observed with TPB stimulation. Our results differ from those obtained in slices of the visual cortex where low-frequency stimulation at 1 Hz was found to induce depression, whereas a TPB protocol (10-ms interpulse interval) had no effect (Kirkwood and Bear 1994). Whether this difference reflects regional specificity or a difference between in vitro and in vivo preparations has yet to be determined. The similarity in the amplitude and time course of potentiation observed with all three low-frequency stimulus protocols tested here (single pulse, paired pulse, and TPB) strongly suggests that repeated low-frequency stimulation is responsible for the effect in the PFC. This form of low-amplitude and persistent potentiation was observed both on unpotentiated and depotentiated synapses, but not on synapses that have been maximally potentiated, and it did not increase the amount of LTP that can be induced by strong tetanic stimulation. These results suggest that potentiation induced by low-frequency stimulation occludes LTP at least partially, and thus may share some common mechanisms with LTP. One possibility is a reduction in GABAergic inhibition during low-frequency stimulation (Davies and Collingridge 1993; McCarren and Alger 1985; Thompson and Gähwiler 1989), which may provide the conditions for increased NMDA receptor activation during electrical stimulation of this pathway.
; Wexler and Stanton 1993). Thus TPB stimulation selectively induces depotentiation, but not LTD, in the hippocampo-PFC pathway in vivo. After TPB stimulation, however, the response slightly increased, before reaching a stable depotentiated level. Although this may reflect incomplete depotentiation, we believe TPB stimulation induced slow-onset potentiation in depotentiated synapses, as previously observed in unpotentiated synapses. The same stimulus pattern, therefore, would produce opposite and, in the case of LTP reversal, summated effects. This is similar to the effect found in guinea pig hippocampal slices, where 5-Hz stimulation can induce a small amount of potentiation at naive synapses and reverse LTP (O'Dell and Kandel 1994), and to that of theta-burst stimulation in area CA1 of the rat hippocampal slice, although in this case different intensities were required for the selective induction of LTP or depotentiation (Barr et al. 1995).
reported that a low-frequency stimulus pattern consisting of pairs (25-ms intervals) of TPBs at short intervals (2.5-5 ms) induces LTD in the perforant path-dentate gyrus synapses in vivo, a system in which neither single-pulse nor paired-pulse low-frequency stimulation was found to induce LTD or depotentiation (Errington et al. 1995). In this pathway, the efficacy of the former protocol was attributed in part to the ability of the two pulses at very short intervals to increase the NMDA-receptor-mediated component of the excitatory postsynaptic potential (Blanpied and Berger 1992; Thiels et al. 1996). Although the profile observed in the hippocampo-PFC pathway is different from that in the dentate gyrus, because we observed depotentiation but not LTD, we suggest that the selective efficacy of this protocol in inducing depotentiation in the PFC is due to the requirement for enhanced NMDA receptor activation provided by the TPB paradigm. The relative contribution of NMDA receptor activation and of the level of inhibition in mediating depotentiation in the PFC remains to be investigated. It is interesting to note, however, that depotentiation in the PFC does not require patterns of stimulation associated with substantial inhibition, such as with pairs of either single or burst pulses at 25- to 35-ms intervals. Thus depotentiation in the PFC may primarily rely on a moderate NMDA receptor activation leading to a rise in intracellular Ca2+ that is below the threshold for inducing LTP (Artola and Singer 1993; Bear et al. 1987; Lisman 1989).
| |
FOOTNOTES |
|---|
Address for reprint requests: F. Burette, Laboratoire de Neurobiologie de l'Apprentissage et de la Mémoire, CNRS URA 1491, Université Paris Sud, Bât. 446, 91405 Orsay Cedex, France.
Received 11 March 1997; accepted in final form 29 April 1997.
| |
REFERENCES |
|---|
|
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
This article has been cited by other articles:
|
|
 |
|
  Y. S. Jo, E. H. Park, I. H. Kim, S. K. Park, H. Kim, H. T. Kim, and J.-S. Choi The Medial Prefrontal Cortex Is Involved in Spatial Memory Retrieval under Partial-Cue Conditions J. Neurosci., December 5, 2007; 27(49): 13567 - 13578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kumar, J. S. Thinschmidt, T. C. Foster, and M. A. King Aging Effects on the Limits and Stability of Long-Term Synaptic Potentiation and Depression in Rat Hippocampal Area CA1 J Neurophysiol, August 1, 2007; 98(2): 594 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Floresco and M. T. Tse Dopaminergic Regulation of Inhibitory and Excitatory Transmission in the Basolateral Amygdala-Prefrontal Cortical Pathway J. Neurosci., February 21, 2007; 27(8): 2045 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Kramar, B. Lin, C. S. Rex, C. M. Gall, and G. Lynch Integrin-driven actin polymerization consolidates long-term potentiation PNAS, April 4, 2006; 103(14): 5579 - 5584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Maroun and G. Richter-Levin Exposure to Acute Stress Blocks the Induction of Long-Term Potentiation of the Amygdala-Prefrontal Cortex Pathway In Vivo J. Neurosci., June 1, 2003; 23(11): 4406 - 4409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Floresco and A. A. Grace Gating of Hippocampal-Evoked Activity in Prefrontal Cortical Neurons by Inputs from the Mediodorsal Thalamus and Ventral Tegmental Area J. Neurosci., May 1, 2003; 23(9): 3930 - 3943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kourrich and C. A. Chapman NMDA Receptor-Dependent Long-Term Synaptic Depression in the Entorhinal Cortex In Vitro J Neurophysiol, April 1, 2003; 89(4): 2112 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Huang, Y.-C. Liang, and K.-S. Hsu Characterization of the Mechanism Underlying the Reversal of Long Term Potentiation by Low Frequency Stimulation at Hippocampal CA1 Synapses J. Biol. Chem., December 14, 2001; 276(51): 48108 - 48117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Floresco, C. D. Blaha, C. R. Yang, and A. G. Phillips Dopamine D1 and NMDA Receptors Mediate Potentiation of Basolateral Amygdala-Evoked Firing of Nucleus Accumbens Neurons J. Neurosci., August 15, 2001; 21(16): 6370 - 6376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Froc, C. A. Chapman, C. Trepel, and R. J. Racine Long-Term Depression and Depotentiation in the Sensorimotor Cortex of the Freely Moving Rat J. Neurosci., January 1, 2000; 20(1): 438 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gurden, M. Takita, and T. M. Jay Essential Role of D1 But Not D2 Receptors in the NMDA Receptor-Dependent Long-Term Potentiation at Hippocampal-Prefrontal Cortex Synapses In Vivo J. Neurosci., November 15, 2000; 20(22): RC106 - RC106. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
