Short- and Long-Term Plasticity of the Perforant Path Synapse in Hippocampal Area CA3

2002 ◽  
Vol 88 (1) ◽  
pp. 528-533 ◽  
Author(s):  
David B.T. McMahon ◽  
German Barrionuevo
Keyword(s):  
Mossy Fiber ◽  
Activity Patterns ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Cortical Input ◽  
Efficient Retrieval ◽  
Recurrent Collateral

The direct perforant path (PP) projection to CA3 is a major source of cortical input to the hippocampal region, yet relatively little is known about the basic properties of physiology and plasticity in this pathway. We tested whether PP long-term potentiation (LTP) in CA3 possesses the Hebbian property of associativity; i.e., whether the firing of fibers of different orders can induce PP LTP. We stimulated PP with weak trains of high-frequency stimulation (HFS), which by itself was below the threshold for LTP induction. The identical HFS was effective in inducing LTP when the mossy fiber pathway (MF) was activated simultaneously, thus demonstrating associative plasticity between the two pathways. We also demonstrated associative LTP between PP and recurrent collateral fibers (RC). PP LTP was blocked by the N-methyl-d-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid in both the associative and homosynaptic induction conditions. Neither MF nor RC fiber HFS alone resulted in permanent changes in PP field excitatory postsynaptic potential (fEPSP) amplitude. However, HFS delivered to either MF or RC alone led to transient heterosynaptic depression of the PP fEPSP. Our results support the conceptual framework that regards CA3 as an autoassociative memory network in which efficient retrieval of previously stored activity patterns is mediated by associative plasticity of the PP synapse.

Long-Term Depression in Identified Stellate Neurons of Juvenile Rat Entorhinal Cortex

2007 ◽  
Vol 97 (1) ◽  
pp. 727-737 ◽  
Author(s):  
Pan-Yue Deng ◽  
Saobo Lei
Keyword(s):  
Entorhinal Cortex ◽  
Molecular Mechanisms ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Cellular Mechanism ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Cortical Input ◽  
Frequency Stimulation

The entorhinal cortex (EC) serves as a gateway to the hippocampus and plays a pivotal role in memory processing in the brain. Superficial layers of the EC convey the cortical input projections to the hippocampus, whereas deep layers of the EC relay hippocampal output projections back to the superficial layers of the EC or to other cortical regions. Whereas the EC expresses long-term potentiation (LTP) and depression (LTD), the underlying cellular and molecular mechanisms have not been determined. Because the axons of the stellate neurons in layer II of the EC form the perforant path that innervates the dentate gyrus granule cells of the hippocampus, we studied the mechanisms underlying the long-term plasticity in identified stellate neurons. Application of high-frequency stimulation (100 Hz for 1 s, repeated 3 times at an interval of 10 s) or forskolin (50 μM) failed to induce significant changes in synaptic strength, whereas application of pairing (presynaptic stimulation at 0.33 Hz paired with postsynaptic depolarization from −60 to −10 mV for 5 min) or low-frequency stimulation (LFS, 1 Hz for 15 min) paradigm-induced LTD. Pairing- or LFS-induced LTDs were N-methyl-d-aspartate receptor-dependent and occluded each other suggesting that they have the similar cellular mechanism. Pairing-induced LTD required the activity of calcineurin and involved AMPA receptor endocytosis that required the function of ubiquitin–proteasome system. Our study provides a cellular mechanism that might in part explain the role of the EC in memory.

scholarly journals Metabotropic Glutamate Receptor Antagonist AIDA Blocks Induction of Mossy Fiber-CA3 LTP In Vivo

2005 ◽  
Vol 93 (5) ◽  
pp. 2668-2673 ◽  
Author(s):  
Kenira J. Thompson ◽  
Mario L. Mata ◽  
James E. Orfila ◽  
Edwin J. Barea-Rodriguez ◽  
Joe L. Martinez
Keyword(s):  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Initial Slope ◽  
Maximal Response ◽  
Excitatory Postsynaptic Potential ◽  
Sprague Dawley ◽  
Metabotropic Glutamate ◽  
Term Potentiation

Metabotropic glutamate receptors (mGluR) are implicated in long-term memory storage. mGluR-I and mGluR-II antagonists impede various forms of learning and long-term potentiation (LTP) in animals. Despite the evidence linking mGluR to learning mechanisms, their role in mossy fiber-CA3 long-term potentiation (LTP) is not yet clear. To explain the involvement of mGluR-I in memory mechanisms, we examined the function of the mGluR-I antagonist 1-aminoindan-1, 5-dicarboxylic acid (AIDA) on the induction of mossy fiber-CA3 LTP in vivo in male Sprague Dawley and Fischer 344 (F344) rats. Acute extracellular mossy fiber (MF) responses were evoked by stimulation of the MF bundle and recorded in the stratum lucidum of CA3. The excitatory postsynaptic potential (EPSP) magnitude was measured by using the initial slope of the field EPSP slope measured 2–3 ms after response onset. After collection of baseline MF-CA3 responses at 0.05 Hz, animals received either ((±))-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ( N-methyl-d-aspartate-R antagonist, 10 mg/kg ip), naloxone (opioid-R antagonist, 10 mg/kg ip), or AIDA (mGluR antagonist, 1 mg/kg ip or 37.5 nmol ic). LTP was induced by two 100-Hz trains at the intensity sufficient to evoke 50% of the maximal response. Responses were collected for an additional 1 h. AIDA blocked induction of LTP in the mossy fiber pathway ( P < 0.05) in both strains of rats after systemic and in Sprague Dawley rats after intrahippocampal injection.

scholarly journals Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

2018 ◽  
Vol 115 (20) ◽  
pp. E4670-E4679 ◽  
Author(s):  
Tassilo Jungenitz ◽  
Marcel Beining ◽  
Tijana Radic ◽  
Thomas Deller ◽  
Hermann Cuntz ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Molecular Layer ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Spatial Learning And Memory ◽  
Heterosynaptic Plasticity ◽  
Spine Plasticity

Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.

Long-Term Potentiation in the Dentate Gyrus Is Not Linked to Increased Extracellular Glutamate Concentration

1999 ◽  
Vol 81 (4) ◽  
pp. 1741-1748 ◽  
Author(s):  
T. M. Jay ◽  
E. Zilkha ◽  
T. P. Obrenovitch
Keyword(s):  
Dentate Gyrus ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Mammalian Brain ◽  
Excitatory Postsynaptic Potential ◽  
Extracellular Glutamate ◽  
Glutamate Concentration ◽  
Term Potentiation

Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration. Long-term potentiation (LTP) of excitatory transmission is a likely candidate for the encoding and storage of information in the mammalian brain. There is a general agreement that LTP involves an increase in synaptic strength, but the mechanisms underlying this persistent change are unclear and controversial. Synaptic efficacy may be enhanced because more transmitter glutamate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular glutamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection of any putative change in extracellular glutamate associated with LTP, our experimental strategy included the following features. 1) Two separate series of experiments were carried out with animals under pentobarbital or urethan anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsynaptic potential evoked by activation of the perforant path were recorded precisely at the same site. Tetanic stimulation of the perforant path increased persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results do not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data supporting the notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft conflict with the hypothesis that LTP could also involve a broad synaptic spillover of glutamate.

Heterosynaptic LTD and Depotentiation in the Medial Perforant Path of the Dentate Gyrus in the Freely Moving Rat

1997 ◽  
Vol 77 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Valérie Doyère ◽  
Bolek Srebro ◽  
Serge Laroche
Keyword(s):  
Dentate Gyrus ◽  
High Frequency ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Tetanic Stimulation ◽  
Frequency Stimulation ◽  
Freely Moving ◽  
Stimulation Of

Doyère, Valérie, Bolek Srebro, and Serge Laroche. Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J. Neurophysiol. 77: 571–578, 1997. We examined the characteristics of heterosynaptic long-term depression (LTD) and depotentiation of previously established long-term potentiation (LTP) in the medial and lateral entorhinal afferents to the dentate gyrus in the awake rat. Rats were prepared for chronic recording of dentate gyrus evoked potentials to activation of the medial and lateral perforant paths. This study in awake rats confirms that heterosynaptic LTD can be induced at inactive medial perforant path synapses in conjunction with the induction of LTP produced by high-frequency stimulation of the lateral perforant path. This form of LTD was long lasting and reversible by tetanic stimulation delivered to the depressed pathway. In contrast, tetanic stimulation of the medial perforant path had only a small heterosynaptic effect on the lateral pathway, suggesting that the two input pathways to the dentate gyrus are not symmetrical in their ability to induce heterosynaptic LTD. We also examined the ability of high-frequency stimulation of one pathway to produce depotentiation of the other pathway. We found that when LTP was first induced in the medial perforant path, depotentiation was induced heterosynaptically by tetanization of the lateral pathway. Both newly established LTP (30 min) and LTP induced and saturated by repeated tetanic stimulation over several days can be depotentiated heterosynaptically. Moreover, depotentiation of the medial perforant path synapses was found to be linearly correlated with the magnitude of LTP induced in the lateral perforant path synapses, and subsequent tetanic stimulation of the depotentiated medial perforant path restored LTP to an extent that counterbalanced depotentiation. The saturation and repotentiation experiments provide clear support for the conclusion that the rapid reversal of LTP reflects true depotentiation of the medial input. Again, as with heterosynaptic LTD, tetanization of the medial perforant path had little effect on previously induced LTP in the lateral path. These results provide evidence that medial perforant path synapses can be depressed and depotentiated heterosynaptically. They suggest that in the intact rat synaptic changes in the afferents to the dentate gyrus from the lateral entorhinal cortex exert powerful control over ongoing or recent synaptic plasticity in the medial entorhinal afferents.

Low-frequency stimulation of the perforant path produces long-term potentiation in the dentate gyrus of unanesthetized rats

1983 ◽  
Vol 61 (10) ◽  
pp. 1156-1161 ◽  
Author(s):  
R. W. Skelton ◽  
J. J. Miller ◽  
A. G. Phillips
Keyword(s):  
Dentate Gyrus ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
Frequency Stimulation ◽  
Stimulation Of

Brief periods of high-frequency stimulation of hippocampal afferents produce long-term potentiation (LTP) of synaptic transmission, but the minimum frequency capable of inducing this alteration in synaptic efficacy has not been specified. The present study used the repeated measurement of input–output curves in the perforant path – dentate gyrus system of freely moving rats to monitor synaptic efficacy and found that stimulation at 0.2 Hz, but not 0.04 Hz produced LTP. These results suggest that the minimum stimulation frequency capable of producing LTP is lower than previously described. Possible reasons for the discrepancy between the present and previous findings are discussed, along with the implications of low-frequency potentiation.

scholarly journals Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Mei Yuan ◽  
Thomas Meyer ◽  
Christoph Benkowitz ◽  
Shakuntala Savanthrapadian ◽  
Laura Ansel-Bollepalli ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Spatial Information ◽  
Molecular Layer ◽  
Activity Patterns ◽  
Long Term Potentiation ◽  
Medial Septum ◽  
Perforant Path ◽  
Term Potentiation ◽  
Memory Acquisition

Somatostatin-expressing-interneurons (SOMIs) in the dentate gyrus (DG) control formation of granule cell (GC) assemblies during memory acquisition. Hilar-perforant-path-associated interneurons (HIPP cells) have been considered to be synonymous for DG-SOMIs. Deviating from this assumption, we show two functionally contrasting DG-SOMI-types. The classical feedback-inhibitory HIPPs distribute axon fibers in the molecular layer. They are engaged by converging GC-inputs and provide dendritic inhibition to the DG circuitry. In contrast, SOMIs with axon in the hilus, termed hilar interneurons (HILs), provide perisomatic inhibition onto GABAergic cells in the DG and project to the medial septum. Repetitive activation of glutamatergic inputs onto HIPP cells induces long-lasting-depression (LTD) of synaptic transmission but long-term-potentiation (LTP) of synaptic signals in HIL cells. Thus, LTD in HIPPs may assist flow of spatial information from the entorhinal cortex to the DG, whereas LTP in HILs may facilitate the temporal coordination of GCs with activity patterns governed by the medial septum.

scholarly journals Irradiation of the Juvenile Brain Provokes a Shift from Long-Term Potentiation to Long-Term Depression

2015 ◽  
Vol 37 (3) ◽  
pp. 263-272 ◽  
Author(s):  
Giulia Zanni ◽  
Kai Zhou ◽  
Ilse Riebe ◽  
Cuicui Xie ◽  
Changlian Zhu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Young Patients ◽  
Long Term Potentiation ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Long Term Depression ◽  
Term Potentiation

Radiotherapy is common in the treatment of brain tumors in children but often causes deleterious, late-appearing sequelae, including cognitive decline. This is thought to be caused, at least partly, by the suppression of hippocampal neurogenesis. However, the changes in neuronal network properties in the dentate gyrus (DG) following the irradiation of the young, growing brain are still poorly understood. We characterized the long-lasting effects of irradiation on the electrophysiological properties of the DG after a single dose of 6-Gy whole-brain irradiation on postnatal day 11 in male Wistar rats. The assessment of the basal excitatory transmission in the medial perforant pathway (MPP) by an examination of the field excitatory postsynaptic potential/volley ratio showed an increase of the synaptic efficacy per axon in irradiated animals compared to sham controls. The paired-pulse ratio at the MPP granule cell synapses was not affected by irradiation, suggesting that the release probability of neurotransmitters was not altered. Surprisingly, the induction of long-term synaptic plasticity in the DG by applying 4 trains of high-frequency stimulation provoked a shift from long-term potentiation (LTP) to long-term depression (LTD) in irradiated animals compared to sham controls. The morphological changes consisted in a virtually complete ablation of neurogenesis following irradiation, as judged by doublecortin immunostaining, while the inhibitory network of parvalbumin interneurons was intact. These data suggest that the irradiation of the juvenile brain caused permanent changes in synaptic plasticity that would seem consistent with an impairment of declarative learning. Unlike in our previous study in mice, lithium treatment did unfortunately not ameliorate any of the studied parameters. For the first time, we show that the effects of cranial irradiation on long-term synaptic plasticity is different in the juvenile compared with the adult brain, such that while irradiation of the adult brain will only cause a reduction in LTP, irradiation of the juvenile brain goes further and causes LTD. Although the mechanisms underlying the synaptic alterations need to be elucidated, these findings provide a better understanding of the effects of irradiation in the developing brain and the cognitive deficits observed in young patients who have been subjected to cranial radiotherapy.

Interaction Between Tetanus Long-Term Potentiation and Hypoxia-Induced Potentiation in the Rat Hippocampus

1997 ◽  
Vol 78 (5) ◽  
pp. 2475-2482 ◽  
Author(s):  
M. Lyubkin ◽  
D. M. Durand ◽  
M. A. Haxhiu
Keyword(s):  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Rat Hippocampus ◽  
Magnesium Concentration ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Specificity ◽  
Term Potentiation ◽  
Neuronal Processing

Lyubkin, M., D. M. Durand, and M. A. Haxhiu. Interaction between tetanus long-term potentiation and hypoxia-induced potentiation in the rat hippocampus. J. Neurophysiol. 78: 2475–2482, 1997. The interaction between tetanus-induced long-term potentiation (LTP) and hypoxia-induced potentiation was investigated by performing extracellular recordings in the CA1 region of rat hippocampus using a two-pathway design. Hippocampal slices were placed in an interface chamber containing artificial cerebrospinal fluid (ACSF) solution with high magnesium concentration. Hypoxia was induced by replacing the 5% CO2-95% O2 gas mixture with 5% CO2-95% N2 for 2 min. Tetanus-LTP was induced with 1-s, 100-Hz current pulses. Significant hypoxia-induced potentiation of the slope of the dendritic excitatory postsynaptic potential (EPSP) was found in ACSF containing 2 mM of magnesium 2, 27 ± 10% (mean ± SE; n = 16; P < 0.01) with no change in the mean amplitude of the presynaptic volley. All experiments in which a stable control baseline was obtained were used for data analysis. The data show that short episodes (2 min) of hypoxia can induce LTP of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated synaptic transmission. The present study demonstrated that after tetanus-LTP, 33 ± 3% ( n = 10; P < 0.01), hypoxia further potentiated the field EPSP slopes by a mean value of 16 ± 5% ( n = 10; P < 0.05). Moreover, using a two-pathway design, we showed that hypoxia produced similar potentiation in both the control [19 ± 5%; n = 10; P < 0.01) and tetanus-induced LTP pathway, and the total potentiation produced by a combination of tetanus then hypoxia, 63 ± 13% ( n = 10; p < 0.01), was significantly larger ( P < 0.01) than hypoxia alone. These data suggest that hypoxia-induced potentiation is additive with tetanus-LTP. Occlusion experiments were performed to verify whether the mechanisms responsible for hypoxia-induced potentiation are independent of preexisting synaptic levels induced by high-frequency stimulation. Hypoxia produced significant potentiation (23 ± 7%; n = 7; P < 0.05) after successful occlusion of the LTP pathway. Therefore, because the magnitude of hypoxia-induced potentiation is both independent of preexisting synaptic levels and also additive, synaptic specificity associated with LTP is preserved. The magnitude of tetanus-LTP induced 20 min after hypoxia (15 ± 4%; n = 10) was significantly smaller ( P < 0.01) relative to LTP after normoxic conditions (33 ± 3%; n = 10). Additionally, hypoxia blocked the transient, robust potentiation occurring during the early phase of LTP induction. This study suggests that although hypoxia modifies neuronal processing by general excitation, synaptic specificity associated with tetanus-LTP still is preserved. However, hypoxia can disrupt neuronal processing by inhibiting new modification of synaptic transmission.

Differing Mechanisms of Expression for Short- and Long-Term Potentiation

1997 ◽  
Vol 78 (1) ◽  
pp. 321-334 ◽  
Author(s):  
Paul E. Schulz ◽  
Jill C. Fitzgibbons
Keyword(s):  
Synaptic Plasticity ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Induction Step ◽  
Term Potentiation ◽  
Short And Long Term

Schulz, Paul E. and Jill C. Fitzgibbons. Differing mechanisms of expression for short- and long-term potentiation. J. Neurophysiol. 78: 321–334, 1997. Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a cellular mechanism that may contribute to memory storage. It is the sustained phase of population excitatory postsynaptic potential induced by high-frequency stimulation (HFS). HFS can also induce short-term potentiation (STP), a decremental potentiation lasting ∼15 min. It has been unclear whether STP is simply a reversible form of LTP elicited by subthreshold stimuli or whether it is an independently expressed form of synaptic plasticity. We have attempted to clarify the relationship between LTP and STP in the extracellular recording technique in area CA1 of the adult rat hippocampal slice preparation to test four predictions of the hypothesis that LTP and STP are expressed via the same mechanism. First, occluding LTP expression should block STP expression. Saturating LTP under six different conditions, however, did not occlude STP expression. Second, occluding STP expression should occlude LTP expression. The partial or full occlusion of STP by two maneuvers (increasing the stimulus intensity used for HFS or applying 3-isobutyl-1-methylxanthine), however, did not occlude LTP expression. Third, LTP increases and decreases paired-pulse facilitation (PPF), and STP should have the same effect. STP did not change PPF, however. The first three results, then, suggest that STP and LTP are expressed via different mechanisms. Fourth, STP should be maximal near the LTP induction threshold, and then decrease above it. Surprisingly, STP was maximal at or very close to the LTP induction threshold, but it did not decrease above this threshold. This relationship suggests the possibility that STP and LTP share an induction step(s). What is the function of the independently expressed STP? We find that LTP can be induced by two HFSs, each of which is subthreshold for LTP, if the second is given during STP from the first. This suggests that STP can temporarily lower the LTP induction threshold. Three lines of evidence, then, suggest that STP and LTP may be expressed via different mechanisms; however, the proximity of STP saturation to LTP induction suggests that they may share an induction step(s). STP may also have the very important function of temporarily lowering the LTP induction threshold. Finally, these data suggestion caution in interpreting LTP data obtained <20–30 min after HFS, because they may be contaminated by STP, which appears to have different underlying mechanisms.

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