scholarly journals Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases.

1994 ◽  
Vol 1 (2) ◽  
pp. 129-139
Author(s):  
T J O'Dell ◽  
E R Kandel
Keyword(s):  
Synaptic Transmission ◽  
Protein Phosphatases ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Phosphatase Inhibitors ◽  
Ca1 Region ◽  
Protein Phosphatase Inhibitors ◽  
Frequency Stimulation

In the CA1 region of adult guinea pig hippocampal slices, long trains of theta frequency (5 Hz) stimulation produced a small enhancement of basal synaptic transmission but depressed the strength of synaptic transmission at synapses that had recently undergone long-term potentiation (LTP). Five hertz stimulation delivered immediately prior to high-frequency stimulation also inhibited the subsequent induction of LTP. The depression of potentiated synapses by 5 Hz stimulation (depotentiation) was blocked by 2-amino-5-phosphonovalerate and was observed only during the early phases of LTP. Furthermore, the protein phosphatase inhibitors okadaic acid and calyculin A blocked both depotentiation and the ability of 5 Hz stimulation to inhibit subsequent LTP, suggesting that protein phosphatases are involved in the ability of 5 Hz stimulation to modulate synaptic plasticity in the CA1 region of the hippocampus.

scholarly journals Synaptically Released Glutamate Does Not Overwhelm Transporters on Hippocampal Astrocytes During High-Frequency Stimulation

2000 ◽  
Vol 83 (5) ◽  
pp. 2835-2843 ◽  
Author(s):  
Jeffrey S. Diamond ◽  
Craig E. Jahr
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Direct Role ◽  
Ca1 Region ◽  
Frequency Stimulation ◽  
Hippocampal Astrocytes

In addition to maintaining the extracellular glutamate concentration at low ambient levels, high-affinity glutamate transporters play a direct role in synaptic transmission by speeding the clearance of glutamate from the synaptic cleft and limiting the extent to which transmitter spills over between synapses. Transporters are expressed in both neurons and glia, but glial transporters are likely to play the major role in removing synaptically released glutamate from the extracellular space. The role of transporters in synaptic transmission has been studied directly by measuring synaptically activated, transporter-mediated currents (STCs) in neurons and astrocytes. Here we record from astrocytes in the CA1 region of hippocampal slices and elicit STCs with high-frequency (100 Hz) stimulus trains of varying length to determine whether transporters are overwhelmed by stimuli that induce long-term potentiation. We show that, at near-physiological temperatures (34°C), high-frequency stimulation (HFS) does not affect the rate at which transporters clear glutamate from the extrasynaptic space. Thus, although spillover between synapses during “normal” stimulation may compromise the absolute synapse specificity of fast excitatory synaptic transmission, spillover is not exacerbated during HFS. Transporter capacity is diminished somewhat at room temperature (24°C), although transmitter released during brief, “theta burst” stimulation is still cleared as quickly as following a single stimulus, even when transport capacity is partially diminished by pharmacological means.

NMDA-Independent LTP by Adenosine A2 Receptor-Mediated Postsynaptic AMPA Potentiation in Hippocampus

1997 ◽  
Vol 78 (4) ◽  
pp. 1965-1972 ◽  
Author(s):  
Kofi Kessey ◽  
David J. Mogul
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptor ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Common Mechanism ◽  
Excitatory Postsynaptic Potential ◽  
Ca1 Region ◽  
The Brain

Kessey, Kofi and David J. Mogul. NMDA-independent LTP by adenosine A2 receptor-mediated postsynaptic AMPA potentiation in hippocampus. J. Neurophysiol. 78: 1965–1972, 1997. The role of adenosine A2 receptors in normal synaptic transmission and tetanus-induced long-term potentiation (LTP) was tested by stimulation of the Schaffer collateral pathway and recording of the field excitatory postsynaptic potential (EPSP) in the CA1 region of rat transverse hippocampal slices. Activation of adenosine A2 receptors with the A2 agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA; 20 nM) enhanced synaptic transmission during low-frequency test pulses (0.033 Hz). Paired stimulation before and during DPMA exposure indicated no paired-pulse facilitation as a result of A2 activation, suggesting that enhancement was not a result of presynaptic modulation. DPMA enhanced the early phase α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the EPSP. In contrast, DPMA had no effect on the N-methyl-d-aspartate (NMDA) component isolated using low extracellular Mg2+ and the AMPA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM), indicating that the effects of A2 activation on synaptic transmission were mediated by a postsynaptic enhancement of the AMPA response. Activation of adenosine A2 receptors during a brief tetanus (100 Hz, 1 s) increased the level of LTP by 36% over that seen in response to a tetanus under control conditions. DPMA exposure after prior induction of LTP showed no additional potentiation, indicating that the mechanisms that contribute to both types of increases in synaptic transmission share a common mechanism. A slow onset NMDA-independent LTP could be induced by application of a tetanus during perfusion of DPMA with the NMDA blocker AP5 (50 μM). Blockade of L-type Ca channels with nifedipine (10 μM) had no effect on normal synaptic transmission but reduced NMDA-independent LTP by 32%. Very little NMDA-independent LTP could be induced after prior saturation of NMDA-dependent LTP via multiple tetani spaced 10 min apart, indicating that both forms of LTP are eventually convergent on a common mechanism, presumably the postsynaptic AMPA receptor response. Because extracellular adenosine levels are modulated by cellular activity throughout the brain and because adenosine receptor activation can markedly alter levels of synaptic transmission independent of NMDA receptors, adenosine may play an important and complex role as a modulator of synaptic transmission 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.

scholarly journals Cholecystokinin release triggered by NMDA receptors produces LTP and sound–sound associative memory

2019 ◽  
Vol 116 (13) ◽  
pp. 6397-6406 ◽  
Author(s):  
Xi Chen ◽  
Xiao Li ◽  
Yin Ting Wong ◽  
Xuejiao Zheng ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Associative Learning ◽  
Associative Memory ◽  
High Frequency ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK−/−mice lacked neocortical LTP and showed deficits in a cue–cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue–cue associative memory.

Overexpression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions

2006 ◽  
Vol 34 (1) ◽  
pp. 88-90 ◽  
Author(s):  
F. Chee ◽  
A. Mudher ◽  
T.A. Newman ◽  
M. Cuttle ◽  
S. Lovestone ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Axonal Transport ◽  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Clinical Symptoms ◽  
Low Frequency ◽  
Synaptic Dysfunction ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

Synaptic dysfunction is believed to be an early pathological change in neurodegenerative diseases and may cause the earliest clinical symptoms. We have used Drosophila to model a tauopathy in order to analyse the earliest neuronal and synaptic dysfunction. Our work has shown that overexpression of human tau (0N3R) in larval motor neurons causes a disruption of axonal transport and a morphological and functional disruption of NMJs (neuromuscular junctions). Tau-expressing NMJs are smaller with an abnormal structure. Despite abnormal morphology, tau-expressing NMJs retain synaptotagmin expression and can form active zones. Tau-expressing NMJs are functionally abnormal and exhibit disrupted vesicle cycling and synaptic transmission. At low-frequency stimulation (1 Hz), ESPs (evoked synaptic potentials) produced by tau-expressing motor neurons were indistinguishable from wild-type; however, following high-frequency stimulation (50 Hz), ESPs from tau-expressing NMJs were significantly decreased in amplitude. To investigate the mechanism underlying the change in ESPs, we analysed the relative numbers and distribution of mitochondria. This revealed that motor neurons expressing tau had a significant reduction in the number of detectable mitochondria in the pre-synaptic terminal. Our results demonstrate that tau overexpression results in synaptic dysfunction, associated with a reduced complement of functional mitochondria. These findings suggest that disruption of axonal transport and synaptic transmission may be key components of the pathogenic mechanism that underlie neuronal dysfunction in the early stages of tauopathies.

scholarly journals A Comparison of the Dynamics of S100B, S100A1, and S100A6 mRNA Expression in Hippocampal CA1 Area of Rats during Long-Term Potentiation and after Low-Frequency Stimulation

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Pavel D. Lisachev ◽  
Mark B. Shtark ◽  
Olga O. Sokolova ◽  
Vladimir O. Pustylnyak ◽  
Mary Yu. Salakhutdinova ◽  
...  
Keyword(s):  
Mrna Level ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Fold Increase ◽  
Long Term Potentiation ◽  
Low Frequency Stimulation ◽  
Term Potentiation ◽  
Mrna Content ◽  
Frequency Stimulation ◽  
Ca1 Area

The interest in tissue- and cell-specific S100 proteins physiological roles in the brain remains high. However, necessary experimental data for the assessment of their dynamics in one of the most important brain activities, its plasticity, is not sufficient. We studied the expression of S100B, S100A1, and S100A6 mRNA in the subfield CA1 of rat hippocampal slices after tetanic and low-frequency stimulation by real-time PCR. Within 30 min after tetanization, a 2–4 fold increase of the S100B mRNA level was observed as compared to the control (intact slices) or to low-frequency stimulation. Subsequently, the S100B mRNA content gradually returned to baseline. The amount of S100A1 mRNA gradually increased during first hour and maintained at the achieved level in the course of second hour after tetanization. The level of S100A6 mRNA did not change following tetanization or low-frequency stimulation.

scholarly journals Disinhibition-assisted LTP in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons

2019 ◽  
Author(s):  
Wataru Ito ◽  
Brendon Fusco ◽  
Alexei Morozov
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation

AbstractNatural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression (LTD), respectively. This approach is effective in many brain areas, but not in the basolateral amygdala (BLA), because the robust local GABAergic tone inside the BLA restricts synaptic plasticity. Here, we identified the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC). Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent, but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses both ex vivo and in vivo. These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.

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