scholarly journals In Vivo Plasticity at Hippocampal Schaffer Collateral-CA1 Synapses: Replicability of the LTP Response and Pharmacology in the Long-Evans Rat

2020 ◽  
Vol 2020 ◽  
pp. 1-24
Author(s):  
A. Ahnaou ◽  
E. White ◽  
R. Biermans ◽  
N. V. Manyakov ◽  
W. H. I. M. Drinkenburg
Keyword(s):  
Synaptic Plasticity ◽  
Acetylcholinesterase Inhibitor ◽  
Nmda Antagonist ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
High Frequency Stimulation ◽  
Schaffer Collateral ◽  
Maximum Slope ◽  
Cognitive Studies ◽  
Long Evans

Broad issues associated with non-replicability have been described in experimental pharmacological and behavioral cognitive studies. Efforts to prevent biases that contribute to non-replicable scientific protocols and to improve experimental rigor for reproducibility are increasingly seen as a basic requirement for the integrity of scientific research. Synaptic plasticity, encompassing long-term potentiation (LTP), is believed to underlie mechanisms of learning and memory. The present study was undertaken in Long-Evans (LE) rats, a strain of rat commonly used in cognitive behavioral tests, to (1) compare three LTP tetanisation protocols, namely, the high-frequency stimulation (HFS), the theta-burst stimulation (TBS), and the paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 stratum radiatum synapse and to (2) assess sensitivity to acute pharmacology. Results: (1) When compared to Sprague-Dawley (SD) rats, the HFS using a stimulus intensity of 50% of the maximum slope obtained from input/output (I/O) curves elicited lower and higher thresholds of synaptic plasticity responses in SD and LE rats, respectively. The 2-train TBS protocol significantly enhanced the LTP response in LE rats over the 5- and 10-train TBS protocols in both strains, and the 5 × TBS protocol inducing a subthreshold LTP response was used in subsequent pharmacological studies in LE rats. The PPF protocol, investigating the locus of the LTP response, showed no difference for the selected interstimulus intervals. (2) Scopolamine, a nonspecific muscarinic antagonist, had a subtle effect, whereas donepezil, an acetylcholinesterase inhibitor, significantly enhanced the LTP response, demonstrating the sensitivity of the TBS protocol to enhanced cholinergic tone. MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, significantly reduced LTP response, while memantine, another NMDA antagonist, had no effect on LTP response, likely associated with a weaker TBS protocol. PQ10, a phosphodiesterase-10 inhibitor, significantly enhanced the TBS-induced LTP response, but did not change the PPF response. Overall, the results confirm the strain-dependent differences in the form of synaptic plasticity, replicate earlier plasticity results, and report effective protocols that generate a relatively subthreshold margin of LTP induction and maintenance, which are suitable for pharmacology in the LE rat strain mainly used in cognitive studies.

scholarly journals Calcium-permeable AMPA receptors mediate timing-dependent LTP elicited by 6 coincident action potentials at Schaffer collateral-CA1 synapses

2019 ◽  
Author(s):  
Efrain A. Cepeda-Prado ◽  
Babak Khodaie ◽  
Gloria D. Quiceno ◽  
Swantje Beythien ◽  
Volkmar Leßmann ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Action Potential ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
High Frequency Stimulation ◽  
Single Trial ◽  
Schaffer Collateral ◽  
Frequency Stimulation

AbstractActivity-dependent synaptic plasticity in neuronal circuits represents a cellular model of memory formation. Such changes can be elicited by repeated high-frequency stimulation inducing long-term potentiation (LTP), or by low frequency stimulation induced long-term depression (LTD). Spike timing-dependent plasticity (STDP) can induce equally robust long-lasting timing-dependent LTP (t-LTP) in response to low frequency repeats of coincident action potential (AP) firing in presynaptic cells followed by postsynaptic neurons. Conversely, this stimulation can lead to t-LTD if the postsynaptic spike precedes the presynaptic action potential. STDP is best suited to investigate synaptic plasticity mechanisms at the single cell level. Commonly, STDP paradigms relying on 25-100 repeats of coincident pre- and postsynaptic firing are used to elicit t-LTP or t-LTD. However, the minimum number of repeats required for successful STDP induction, which could account for fast single trial learning in vivo, is barely explored. Here, we examined low repeat STDP at Schaffer collateral-CA1 synapses by pairing one presynaptic AP with either one postsynaptic AP (1:1 t-LTP) or a burst of 4 APs (1:4 t-LTP). We found 3-6 repeats to be sufficient to elicit t-LTP. Postsynaptic Ca2+ elevation for 1:1 t-LTP required NMDARs and L-type VGCCs, while 1:4 t-LTP depended on metabotropic GluR and ryanodine receptor signaling. Surprisingly, both 6x t-LTP variants were strictly dependent on activation of postsynaptic Ca2+-permeable AMPARs. Both t-LTP forms were regulated differentially by dopamine receptors, but occurred independent from BDNF/TrkB signaling. Our data show that synaptic changes induced by only 3-6 repeats of mild STDP stimulation occuring in ≤10 s can take place on time scales observed also during single trial learning.

scholarly journals Imaging spatio-temporal patterns of long-term potentiation in mouse hippocampus

2003 ◽  
Vol 358 (1432) ◽  
pp. 689-693 ◽  
Author(s):  
Toshiyuki Hosokawa ◽  
Masaki Ohta ◽  
Takeshi Saito ◽  
Alan Fine
Keyword(s):  
Hippocampal Slices ◽  
Temporal Patterns ◽  
Long Term Potentiation ◽  
Optical Recording ◽  
Stratum Radiatum ◽  
High Frequency Stimulation ◽  
Optical Signals ◽  
Term Potentiation ◽  
Spatio Temporal

Spatio-temporal patterns of neuronal activity before and after the induction of long-term potentiation in mouse hippocampal slices were studied using a real-time high-resolution optical recording system. After staining the slices with voltage-sensitive dye, transmitted light images and extracellular field potentials were recorded in response to stimuli applied to CA1 stratum radiatum. Optical and electrical signals in response to single test pulses were enhanced for at least 30 minutes after brief high-frequency stimulation at the same site. In two-pathway experiments, potentiation was restricted to the tetanized pathway. The optical signals demonstrated that both the amplitude and area of the synaptic response were increased, in patterns not predictable from the initial, pretetanus, pattern of activation. Optical signals will be useful for investigating spatio-temporal patterns of synaptic enhancement underlying information storage in the brain.

scholarly journals Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Enrico Faldini ◽  
Tariq Ahmed ◽  
Luc Bueé ◽  
David Blum ◽  
Detlef Balschun
Keyword(s):  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Synaptic Loss ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Frequency Stimulation

AbstractMany mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

Synaptic mechanisms underlying thalamic activation-induced plasticity in the rat auditory cortex

2014 ◽  
Vol 111 (9) ◽  
pp. 1746-1758 ◽  
Author(s):  
Zhi-ru Zhu ◽  
Fenglian Xu ◽  
Wei-gang Ji ◽  
Shuan-cheng Ren ◽  
Fang Chen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Auditory Cortex ◽  
Frequency Tuning ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Medial Geniculate ◽  
Synaptic Mechanisms

Electrical stimulation of ventral division of medial geniculate body (MGBv) neurons evokes a shift of the frequency-tuning curves of auditory cortical (AC) neurons toward the best frequency (BF) of the stimulated MGBv neurons (frequency-specific plasticity). The shift of BF is induced by inhibition of responses at the BF of the recorded AC neuron, with coincident facilitation of responses at the BF of the stimulated MGBv neuron. However, the synaptic mechanisms are not yet understood. We hypothesize that activation of thalamocortical synaptic transmission and receptor function may contribute to MGBv stimulation-induced frequency-specific auditory plasticity and the shift of BF. To test this hypothesis, we measured changes in the excitatory postsynaptic currents in pyramidal neurons of layer III/IV in the auditory cortex following high-frequency stimulation (HFS) of the MGBv, using whole cell recordings in an auditory thalamocortical slice. Our data showed that in response to the HFS of the MGBv the excitatory postsynaptic currents of AC neurons showed long-term bidirectional synaptic plasticity and long-term potentiation and depression. Pharmacological studies indicated that the long-term synaptic plasticity was induced through the activation of different sets of N-methyl-d-aspartate-type glutamatergic receptors, γ-aminobutyric acid-type receptors, and type 5 metabotropic glutamate receptors. Our data further demonstrated that blocking of different receptors with specific antagonists significantly inhibited MGBv stimulation-induced long-term plasticity as well as the shift of BF. These data indicate that these receptors have an important role in mediating frequency-specific auditory cortical plasticity.

scholarly journals Developmental Time Course of SNAP-25 Isoforms Regulate Hippocampal Long-Term Synaptic Plasticity and Hippocampus-Dependent Learning

2020 ◽  
Vol 21 (4) ◽  
pp. 1448
Author(s):  
Katisha R. Gopaul ◽  
Muhammad Irfan ◽  
Omid Miry ◽  
Linnea R. Vose ◽  
Alexander Moghadam ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Time Course ◽  
Splice Variants ◽  
Developmental Regulation ◽  
Release Kinetics ◽  
Long Term Potentiation ◽  
Developmental Time ◽  
Compensatory Mechanisms ◽  
Schaffer Collateral

SNAP-25 is essential to activity-dependent vesicle fusion and neurotransmitter release in the nervous system. During early development and adulthood, SNAP-25 appears to have differential influences on short- and long-term synaptic plasticity. The involvement of SNAP-25 in these processes may be different at hippocampal and neocortical synapses because of the presence of two different splice variants, which are developmentally regulated. We show here that the isoform SNAP-25a, which is expressed first developmentally in rodent brain, contributes to developmental regulation of the expression of both long-term depression (LTD) and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the hippocampus. In one month old mice lacking the developmentally later expressed isoform SNAP-25b, Schaffer collateral-CA1 synapses showed faster release kinetics, decreased LTP and enhanced LTD. By four months of age, SNAP-25b-deficient mice appeared to have compensated for the lack of the adult SNAP-25b isoform, now exhibiting larger LTP and no differences in LTD compared to wild type mice. Interestingly, learning a hippocampus-dependent task reversed the reductions in LTP, but not LTD, seen at one month of age. In four month old adult mice, learning prevented the compensatory up-regulation of LTD that we observed prior to training. These findings support the hypothesis that SNAP-25b promotes stronger LTP and weakens LTD at Schaffer collateral-CA1 synapses in young mice, and suggest that compensatory mechanisms can reverse alterations in synaptic plasticity associated with a lack of SNAP-25b, once mice reach adulthood.

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.

scholarly journals Reduced Synaptic Plasticity in the Lateral Perforant Path Input to the Dentate Gyrus of Aged C57BL/6 Mice

2003 ◽  
Vol 90 (1) ◽  
pp. 32-38 ◽  
Author(s):  
David J. Froc ◽  
Brennan Eadie ◽  
Amanda M. Li ◽  
Karl Wodtke ◽  
Maric Tse ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Significant Degree ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
Effects Of Aging

Hippocampal slices obtained from C57BL/6 mice (3–25 mo) were used to investigate the effects of aging on excitatory postsynaptic potentials (EPSPs) elicited in dentate gyrus with lateral perforant path stimulation. The maximal amplitude of the EPSP, as well as the degree of paired-pulse facilitation, was significantly reduced in animals aged 12 mo or more compared with younger animals (<12 mo). Although all animals showed equivalent short-term potentiation (STP) in response to high-frequency stimulation, this did not translate into a long-lasting increase in synaptic efficacy in the older animals. A significant degree of long-term potentiation (LTP) of synaptic efficacy was only observed in animals <12 mo of age when measured 30 min after induction. Blocking GABAA-mediated inhibition significantly enhanced STP in younger and older animals; however, a significant degree of LTP was again only observed in slices taken from younger animals. These data indicate that the lateral perforant path input to the dentate gyrus is altered by the aging process, and that this results in a reduction in the capacity of this input to exhibit long-lasting synaptic plasticity.

scholarly journals Effect of intra-hippocampal injection of human recombinant growth hormone on synaptic plasticity in the nucleus basalis magnocellularis-lesioned aged rats

2017 ◽  
Vol 75 (7) ◽  
pp. 477-483 ◽  
Author(s):  
Maryam Malek ◽  
Alireza Sarkaki ◽  
Saleh Zahedi-Asl ◽  
Yaghoob Farbood ◽  
Ziba Rajaei
Keyword(s):  
Growth Hormone ◽  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Nucleus Basalis ◽  
Vehicle Group ◽  
High Frequency Stimulation ◽  
Nucleus Basalis Magnocellularis ◽  
Term Potentiation ◽  
Intrahippocampal Injection

ABSTRACT In this study, we proposed that administration of hippocampal growth hormone in ageing animals with growth hormone deficiency can compensate long-term potentiation and synaptic plasticity in nucleus basalis magnocellularis (NBM)-lesioned rats. Aged male Wistar rats were randomly divided into six groups (seven in each) of sham-operated healthy rats (Cont); NBM-lesioned rats (L); NBM-lesioned rats and intrahippocampal injection of growth hormone vehicle (L + Veh); NBM-lesioned and intrahippocampal injection of growth hormone (10, 20 and 40 µg.2 µl-1) (L + GH). In vivo electrophysiological recording techniques were used to characterize maintenance of long-term potentiation at distinct times (1, 2, 3, 24 and 48 hours) after high-frequency stimulation. The population spike was enhanced significantly for about 48 hours following tetanic stimulation in rats treated with a dose-dependent growth hormone compared to the vehicle group (p < 0.05), possibly through neuronal plasticity and neurogenesis in affected areas.

scholarly journals Mechanisms of heterosynaptic metaplasticity

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130148 ◽  
Author(s):  
Sarah R. Hulme ◽  
Owen D. Jones ◽  
Clarke R. Raymond ◽  
Pankaj Sah ◽  
Wickliffe C. Abraham
Keyword(s):  
Synaptic Plasticity ◽  
Long Range ◽  
Intercellular Communication ◽  
Atp Hydrolysis ◽  
Long Term Potentiation ◽  
Stratum Radiatum ◽  
Signalling Pathways ◽  
Stratum Oriens ◽  
Term Potentiation

Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed ‘metaplasticity’, which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intra cellular versus inter cellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic metaplasticity.

scholarly journals Functional Metaplasticity of Hippocampal Schaffer Collateral-CA1 Synapses Is Reversed in Chronically Epileptic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Mirko Rehberg ◽  
Timo Kirschstein ◽  
Xiati Guli ◽  
Steffen Müller ◽  
Marco Rohde ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Spatial Information ◽  
Memory Task ◽  
Long Term Potentiation ◽  
Memory Training ◽  
Control Group ◽  
Training Task ◽  
Schaffer Collateral

Spatial learning and associating spatial information with individual experience are crucial for rodents and higher mammals. Hence, studying the cellular and molecular cascades involved in the key mechanism of information storage in the brain, synaptic plasticity, has led to enormous knowledge in this field. A major open question applies to the interdependence between synaptic plasticity and its behavioral correlates. In this context, it has become clear that behavioral aspects may impact subsequent synaptic plasticity, a phenomenon termed behavioral metaplasticity. Here, we trained control and pilocarpine-treated chronically epileptic rats of two different age groups (adolescent and adult) in a spatial memory task and subsequently tested long-term potentiation (LTP) in vitro at Schaffer collateral—CA1 synapses. As expected, memory acquisition in the behavioral task was significantly impaired both in pilocarpine-treated animals and in adult controls. Accordingly, these groups, without being tested in the behavioral training task, showed reduced CA1-LTP levels compared to untrained young controls. Spatial memory training significantly reduced subsequent CA1-LTP in vitro in the adolescent control group yet enhanced CA1-LTP in the adult pilocarpine-treated group. Such training in the adolescent pilocarpine-treated and adult control groups resulted in intermediate changes. Our study demonstrates age-dependent functional metaplasticity following a spatial memory training task and its reversal under pathological conditions.

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