scholarly journals Effects of methamphetamine-induced neurotoxicity on striatal long-term potentiation

2022 ◽  
Author(s):  
Anne S. Gibson ◽  
Peter J. West ◽  
Kristen A. Keefe
Keyword(s):  
Brain Slices ◽  
Long Term Potentiation ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
D1 Receptors ◽  
High Frequency Stimulation ◽  
Term Potentiation ◽  
Dopamine Neurotoxicity ◽  
Dopamine Signaling

Abstract Rationale Methamphetamine (METH) exposure is associated with damage to central monoamine systems, particularly dopamine signaling. Rodent models of such damage have revealed a decrease in the amplitude of phasic dopamine signals and significant striatal dysfunction, including changes in the molecular, system, and behavioral functions of the striatum. Dopamine signaling through D1 receptors promotes corticostriatal long-term potentiation (LTP), a critical substrate of these striatal functions. Objectives Therefore, the purpose of this study was to determine if METH-induced dopamine neurotoxicity would impair D1 receptor-dependent striatal LTP in mice. Methods Mice were treated with a METH binge regimen (4 × 10 mg/kg d,l-methamphetamine, s.c.) that recapitulates all of the known METH-induced neurotoxic effects observed in humans, including dopamine toxicity. Three weeks later, acute brain slices containing either the dorsomedial striatum (DMS) or dorsolateral striatum (DLS) were prepared, and plasticity was assessed using white matter, high-frequency stimulation (HFS), and striatal extracellular electrophysiology. Results Under these conditions, LTP was induced in brain slices containing the DMS from saline-pretreated mice, but not mice with METH-induced neurotoxicity. Furthermore, the LTP observed in DMS slices from saline-pretreated mice was blocked by the dopamine D1 receptor antagonist SCH23390, indicating that this LTP is dopamine D1 receptor-dependent. Finally, acute in vivo treatment of METH-pretreated mice with bupropion (50 mg/kg, i.p.) promoted LTP in DMS slices. Conclusions Together, these studies demonstrate that METH-induced neurotoxicity impairs dopamine D1 receptor-dependent LTP within the DMS and that the FDA-approved drug bupropion restores induction of striatal LTP in mice with METH-induced dopamine neurotoxicity.

scholarly journals Xenon Attenuates Hippocampal Long-term Potentiation by Diminishing Synaptic and Extrasynaptic N -methyl-D-aspartate Receptor Currents

2012 ◽  
Vol 116 (3) ◽  
pp. 673-682 ◽  
Author(s):  
Stephan Kratzer ◽  
Corinna Mattusch ◽  
Eberhard Kochs ◽  
Matthias Eder ◽  
Rainer Haseneder ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
High Frequency ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Field Potentials ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Frequency Stimulation

Background The memory-blocking properties of general anesthetics are of high clinical relevance and scientific interest. The inhalational anesthetic xenon antagonizes N-methyl-D-aspartate (NMDA) receptors. It is unknown if xenon affects long-term potentiation (LTP), a cellular correlate for memory formation. In hippocampal brain slices, the authors investigated in area CA1 whether xenon affects LTP, NMDA receptor-mediated neurotransmission, and intracellular calcium concentrations. Methods In sagittal murine hippocampal brain slices, the authors investigated the effects of xenon on LTP by recording excitatory postsynaptic field potentials. Using fluorometric calcium imaging, the authors tested the influence of xenon on calcium influx during high-frequency stimulation. In addition, using the patch-clamp technique, the xenon effect on synaptic and extrasynaptic NMDA receptors and L-type calcium channels was examined. Results In the absence of xenon, high-frequency stimulation reliably induced LTP and potentiated field potential slopes to (mean ± SEM) 127.2 ± 5.8% (P < 0.001). In the presence of xenon, high-frequency stimulation induced only a short-term potentiation, and field potentials returned to baseline level after 15-20 min (105.9 ± 2.9%; P = 0.090). NMDA receptor-mediated excitatory postsynaptic currents were reduced reversibly by xenon to 65.9 ± 9.4% (P = 0.007) of control. When extrasynaptic receptors were activated, xenon decreased NMDA currents to 58.2 ± 5.8% (P < 0.001). Xenon reduced the increase in intracellular calcium during high-frequency stimulation without affecting L-type calcium channels. Conclusions N-methyl-D-aspartate receptor activation is crucial for the induction of CA1 LTP. Thus, the depression of NMDA receptor-mediated neurotransmission presumably contributes to the blockade of LTP under xenon. Because LTP is assumed to be involved in learning and memory, its blockade might be a key mechanism for xenon's amnestic properties.

scholarly journals Phosphodiesterase 1 Bridges Glutamate Inputs with NO- and Dopamine-Induced Cyclic Nucleotide Signals in the Striatum

2019 ◽  
Vol 29 (12) ◽  
pp. 5022-5036 ◽  
Author(s):  
Dahdjim B Betolngar ◽  
Élia Mota ◽  
Arne Fabritius ◽  
Jacob Nielsen ◽  
Charlotte Hougaard ◽  
...  
Keyword(s):  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
D1 Receptor ◽  
Newborn Mice ◽  
Term Potentiation ◽  
Therapeutic Value ◽  
Camp And Cgmp

Abstract The calcium-regulated phosphodiesterase 1 (PDE1) family is highly expressed in the brain, but its functional role in neurones is poorly understood. Using the selective PDE1 inhibitor Lu AF64196 and biosensors for cyclic nucleotides including a novel biosensor for cGMP, we analyzed the effect of PDE1 on cAMP and cGMP in individual neurones in brain slices from male newborn mice. Release of caged NMDA triggered a transient increase of intracellular calcium, which was associated with a decrease in cAMP and cGMP in medium spiny neurones in the striatum. Lu AF64196 alone did not increase neuronal cyclic nucleotide levels, but blocked the NMDA-induced reduction in cyclic nucleotides indicating that this was mediated by calcium-activated PDE1. Similar effects were observed in the prefrontal cortex and the hippocampus. Upon corelease of dopamine and NMDA, PDE1 was shown to down-regulate the D1-receptor mediated increase in cAMP. PDE1 inhibition increased long-term potentiation in rat ventral striatum, showing that PDE1 is implicated in the regulation of synaptic plasticity. Overall, our results show that PDE1 reduces cyclic nucleotide signaling in the context of glutamate and dopamine coincidence. This effect could have a therapeutic value for treating brain disorders related to dysfunctions in dopamine neuromodulation.

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.

Psychophysical Evidence for Long-Term Potentiation of C-Fiber and Aδ-Fiber Pathways in Humans by Analysis of Pain Descriptors

2007 ◽  
Vol 97 (3) ◽  
pp. 2559-2563 ◽  
Author(s):  
Niels Hansen ◽  
Thomas Klein ◽  
Walter Magerl ◽  
Rolf-Detlef Treede
Keyword(s):  
Pain Perception ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Burning Pain ◽  
Term Potentiation ◽  
C Fiber ◽  
Pain Ratings ◽  
Two Factors ◽  
Pain Descriptors

Long-term potentiation of human pain perception (nociceptive LTP) to single electrical test stimuli was induced by high-frequency stimulation (HFS) of cutaneous nociceptive afferents. Numerical pain ratings and a list of sensory pain descriptors disclosed the same magnitude of nociceptive LTP (23% increase for >60 min, P < 0.001), whereas affective pain descriptors were not significantly enhanced. Factor analysis of the sensory pain descriptors showed that facilitation was restricted to two factors characterized by hot and burning (+41%) and piercing and stinging (+21%, both P < 0.01), whereas a factor represented by throbbing and beating was not significantly increased (+9%, P = 0.47). The increased perception of the burning pain quality for >1 h after HFS is interpreted as a LTP-like facilitation of the conditioned cutaneous C-fiber pathway. Additionally, the increase of the stinging pain quality supplied evidence for facilitation of a sharpness-sensitive Aδ-fiber pathway.

scholarly journals Long-term potentiation: outstanding questions and attempted synthesis

2003 ◽  
Vol 358 (1432) ◽  
pp. 829-842 ◽  
Author(s):  
John Lisman
Keyword(s):  
Low Frequency ◽  
Long Term Potentiation ◽  
Variable Number ◽  
High Frequency Stimulation ◽  
Memory Mechanism ◽  
Post Process ◽  
Term Potentiation ◽  
Contradictory Evidence ◽  
Hippocampal Networks

This article attempts an overview of the mechanism of NMDAR-dependent long-term potentiation (LTP) and its role in hippocampal networks. Efforts are made to integrate information, often in speculative ways, and to identify unresolved issues about the induction, expression and molecular storage processes. The pre/post debate about LTP expression has been particularly difficult to resolve. The following hypothesis attempts to reconcile the available physiological evidence as well as anatomical evidence that LTP increases synapse size. It is proposed that synapses are composed of a variable number of trans-synaptic modules, each having presynaptic release sites and a postsynaptic structure that can be AMPAfied by the addition of a hyperslot assembly that anchors 10-20 AMPA channels. According to a newly developed view of transmission, the quantal response is generated by AMPA channels near the site of vesicle release and so will depend on whether the module where release occurs has been AMPAfied. LTP expression may involve two structurally mediated processes: (i) the AMPAfication of existing modules by addition of hyperslot assemblies: this is a purely postsynaptic process and produces an increase in the probability of an AMPA response, with no change in the NMDA component; and (ii) the addition of new modules: this is a structurally coordinated pre/post process that leads to LTP-induced synapse enlargement and potentiation of the NMDA component owing to an increase in the number of release sites (the number of NMDA channels is assumed to be fixed). The protocol used for LTP induction appears to affect the proportion of these two processes; pairing protocols that involve low-frequency presynaptic stimulation induce only AMPAfication, making LTP purely postsynaptic, whereas high-frequency stimulation evokes both processes, giving rise to a presynaptic component. This model is capable of reconciling much of the seemingly contradictory evidence in the pre/post debate. The structural nature of the postulated changes is relevant to a second debate: whether a CaMKII switch or protein-dependent structural change is the molecular memory mechanism. A possible reconciliation is that a reversible CaMKII switch controls the construction of modules and hyperslot assemblies from newly synthesized proteins.

scholarly journals Sniff-Like Patterned Input Results in Long-Term Plasticity at the Rat Olfactory Bulb Mitral and Tufted Cell to Granule Cell Synapse

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Mahua Chatterjee ◽  
Fernando Perez de los Cobos Pallares ◽  
Alex Loebel ◽  
Michael Lukas ◽  
Veronica Egger
Keyword(s):  
Olfactory Bulb ◽  
Granule Cells ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Term Potentiation ◽  
Presynaptic Release ◽  
Extra Activity ◽  
Hippocampal Theta

During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and tufted cells (MTCs), occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule cells (GCs) mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS) protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts (“single-sniff paradigm”) can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and “single-sniff paradigm”-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse.

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.

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