scholarly journals Bidirectional Long-Term Synaptic Zinc Plasticity at Mouse Glutamatergic Synapses

2018 ◽  
Author(s):  
Nathan W. Vogler ◽  
Thanos Tzounopoulos
Keyword(s):  
Low Frequency ◽  
Dorsal Cochlear Nucleus ◽  
High Frequency Stimulation ◽  
Glutamatergic Synapses ◽  
Zinc Signaling ◽  
Frequency Stimulation ◽  
Zinc Levels ◽  
Group 1

AbstractSynaptic zinc is coreleased with glutamate to modulate neurotransmission in many excitatory synapses. In the auditory cortex, synaptic zinc modulates sound frequency tuning and enhances frequency discrimination acuity. In auditory, visual, and somatosensory circuits, sensory experience causes long-term changes in synaptic zinc levels and/or signaling, termed here synaptic zinc plasticity. However, the mechanisms underlying synaptic zinc plasticity and the effects of this plasticity on long-term glutamatergic plasticity remain unknown. To study these mechanisms, we used male and female mice and employed in vitro and in vivo models in zinc-rich, glutamatergic dorsal cochlear nucleus (DCN) parallel fiber (PF) synapses. High-frequency stimulation of DCN PF synapses induced long-term depression of synaptic zinc signaling (Z-LTD), as evidenced by reduced zinc-mediated inhibition of AMPA receptor (AMPAR) excitatory postsynaptic currents (EPSCs). Low-frequency stimulation induced long-term potentiation of synaptic zinc signaling (Z-LTP), as evidenced by enhanced zinc-mediated inhibition of AMPAR EPSCs. Thus, Z-LTD is a new mechanism of LTP and Z-LTD is a new mechanism of LTP. Pharmacological inhibition of Group 1 metabotropic glutamate receptors (G1 mGluRs) eliminated Z-LTD and Z-LTP. Pharmacological activation of G1 mGluRs induced Z-LTD and Z-LTP, associated with bidirectional changes in presynaptic zinc levels. Finally, exposure of mice to loud sound caused G1 mGluR-dependent Z-LTD in DCN PF synapses, consistent with our in vitro results. Together, we show that G1 mGluR activation is necessary and sufficient for inducing bidirectional long-term synaptic zinc plasticity.Key points summarySynaptic zinc is coreleased with glutamate to modulate neurotransmission and auditory processing. Sensory experience causes long-term changes in synaptic zinc signaling, termed synaptic zinc plasticity.At zinc-containing glutamatergic synapses in the dorsal cochlear nucleus (DCN), we show that high-frequency stimulation reduces synaptic zinc signaling (Z-LTD), whereas low-frequency stimulation increases synaptic zinc signaling (Z-LTP).Group 1 metabotropic glutamate receptor (mGluR) activation is necessary and sufficient to induce Z-LTP and Z-LTD. Z-LTP and Z-LTD are associated with bidirectional changes in presynaptic zinc levels.Sound-induced Z-LTD at DCN synapses requires Group 1 mGluR activation.Bidirectional synaptic zinc plasticity is a previously unknown mechanism of LTP and LTD at zinc-containing glutamatergic synapses.

Robust Changes of Afferent-Induced Excitation in the Rat Spinal Dorsal Horn After Conditioning High-Frequency Stimulation

2000 ◽  
Vol 83 (4) ◽  
pp. 2412-2420 ◽  
Author(s):  
Hiroshi Ikeda ◽  
Tatsuya Asai ◽  
Kazuyuki Murase
Keyword(s):  
Dorsal Horn ◽  
High Frequency ◽  
Low Frequency ◽  
Single Pulse ◽  
High Frequency Stimulation ◽  
Neuronal Excitation ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Stimulation Of

We investigated the neuronal plasticity in the spinal dorsal horn and its relationship with spinal inhibitory networks using an optical-imaging method that detects neuronal excitation. High-intensity single-pulse stimulation of the dorsal root activating both A and C fibers evoked an optical response in the lamina II (the substantia gelatinosa) of the dorsal horn in transverse slices of 12- to 25-day-old rat spinal cords stained with a voltage-sensitive dye, RH-482. The optical response, reflecting the net neuronal excitation along the slice-depth, was depressed by 28% for more than 1 h after a high-frequency conditioning stimulation of A fibers in the dorsal root (3 tetani of 100 Hz for 1 s with an interval of 10 s). The depression was not induced in a perfusion solution containing an NMDA antagonist,dl-2-amino-5-phosphonovaleric acid (AP5; 30 μM). In a solution containing the inhibitory amino acid antagonists bicuculline (1 μM) and strychnine (3 μM), and also in a low Cl−solution, the excitation evoked by the single-pulse stimulation was enhanced after the high-frequency stimulation by 31 and 18%, respectively. The enhanced response after conditioning was depotentiated by a low-frequency stimulation of A fibers (0.2–1 Hz for 10 min). Furthermore, once the low-frequency stimulation was applied, the high-frequency conditioning could not potentiate the excitation. Inhibitory transmissions thus regulate the mode of synaptic plasticity in the lamina II most likely at afferent terminals. The high-frequency conditioning elicits a long-term depression (LTD) of synaptic efficacy under a greater activity of inhibitory amino acids, but it results in a long-term potentiation (LTP) when inhibition is reduced. The low-frequency preconditioning inhibits the potentiation induction and maintenance by the high-frequency conditioning. These mechanisms might underlie robust changes of nociception, such as hypersensitivity after injury or inflammation and pain relief after electrical or cutaneous stimulation.

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.

scholarly journals LTD and LTP at the Developing Retinogeniculate Synapse

2009 ◽  
Vol 102 (6) ◽  
pp. 3082-3090 ◽  
Author(s):  
Jokūbas Žiburkus ◽  
Emily K. Dilger ◽  
Fu-Sun Lo ◽  
William Guido
Keyword(s):  
Optic Tract ◽  
Long Term Potentiation ◽  
Dorsal Lateral Geniculate Nucleus ◽  
High Frequency Stimulation ◽  
Retinal Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation ◽  
Retinogeniculate Synapse

The purpose of the present study was to determine whether retinal activity can support long-term changes in synaptic strength in the developing dorsal lateral geniculate nucleus (LGN) of thalamus. To test for this we made use of a rodent in vitro explant preparation in which retinal afferents and the intrinsic circuitry of the LGN remain intact. We repetitively stimulated the optic tract with a tetanus protocol that approximated the temporal features of spontaneous retinal waves. We found the amplitude of extracellular field potentials evoked by retinal stimulation changed significantly after tetanus and that the polarity of these alterations was related to postnatal age. At a time when substantial pruning of retinal connections occurs (postnatal day 1 [P1] to P14), high-frequency stimulation led to an immediate and long-term depression (LTD). However, at times when pruning wanes and adultlike patterns of connectivity are stabilizing (P16 to P30), the identical form of stimulation produced a modest form of potentiation (long-term potentiation [LTP]). The LTD was unaffected by the bath application of γ-aminobutyric acid type A and N-methyl-d-aspartate receptor antagonists. However, both LTD and LTP were blocked by L-type Ca2+-channel antagonists. Thus the Ca2+ influx associated with L-type channel activation mediates the induction of synaptic plasticity and may signal the pruning and subsequent stabilization of developing retinogeniculate connections.

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.

Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro

2007 ◽  
Vol 97 (3) ◽  
pp. 1887-1902 ◽  
Author(s):  
Yitzhak Schiller ◽  
Yael Bankirer
Keyword(s):  
Electrical Stimulation ◽  
High Frequency ◽  
Brain Slices ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Dependent Manner ◽  
Cellular Mechanisms ◽  
Epileptiform Discharges ◽  
Frequency Stimulation

Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5–30 min of 0.1- to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1–5 s of 25- to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train ( P < 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 ± 21% ( P < 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low- and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 ± 3% after 10-min, 1-Hz stimulation and by 86 ± 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both low- and high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.

Electric Low-Frequency Stimulation of the Tongue Induces Long-Term Depression of the Jaw-Opening Reflex in Anesthetized Mice

2004 ◽  
Vol 92 (6) ◽  
pp. 3332-3337 ◽  
Author(s):  
Jens Ellrich
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Conditioning Stimulation ◽  
Low Frequency Stimulation ◽  
Jaw Opening ◽  
Jaw Opening Reflex ◽  
Frequency Stimulation ◽  
Stimulation Of

Long-term depression (LTD) of somatosensory processing has been demonstrated in slice preparations of the spinal dorsal horn. Although LTD could be reliably induced in vitro, inconsistent results were encountered when the same types of experiments were conducted in adult animals in vivo. We addressed the hypothesis that LTD of orofacial sensorimotor processing can be induced in mice under general anesthesia. The effects of electric low- and high-frequency conditioning stimulation of the tongue on the sensorimotor jaw-opening reflex (JOR) elicited by electric tongue stimulation were investigated. Low-frequency stimulation induced a sustained decrease of the reflex integral for ≥1 h after the end of conditioning stimulation. After additional high-frequency stimulation, the reflex partly recovered from LTD. High-frequency stimulation alone induced a transient increase of the JOR integral for <10 min. The LTD of the sensorimotor jaw-opening reflex in anesthetized mice may be an appropriate model to investigate the central mechanisms and the pharmacology of synaptic plasticity in the orofacial region. The application of electrophysiological techniques in mice provides the opportunity to include adequate knock-out models to elucidate the neurobiology of LTD.

Sign in / Sign up

Export Citation Format

Share Document