Long-Term Potentiation Alters the Modulator Pharmacology of AMPA-Type Glutamate Receptors

2002 ◽  
Vol 87 (6) ◽  
pp. 2790-2800 ◽  
Author(s):  
Bin Lin ◽  
Fernando A. Brücher ◽  
Laura Lee Colgin ◽  
Gary Lynch
Keyword(s):  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Drug Infusion ◽  
Adult Rats ◽  
Receptor Kinetics ◽  
Postsynaptic Currents ◽  
Term Potentiation

Changes in the biophysical properties of AMPA-type glutamate receptors have been proposed to mediate the expression of long-term potentiation (LTP). The present study tested if, as predicted from this hypothesis, AMPA receptor modulators differentially affect potentiated versus control synaptic currents. Whole cell recordings were collected from CA1 pyramidal neurons in hippocampal slices from adult rats. Within-neuron comparisons were made of the excitatory postsynaptic currents (EPSCs) elicited by two separate groups of Schaffer-collateral/commissural synapses. LTP was induced by theta burst stimulation in one set of inputs; cyclothiazide (CTZ), a drug that acts on the desensitization kinetics of AMPA receptors, was infused 30 min later. The decay time constants of the potentiated EPSCs prior to drug infusion were slightly, but significantly, shorter than those of control EPSCs. CTZ slowed the decay of the EPSCs, as reported in prior studies, and did so to a significantly greater degree in the potentiated synapses. Additionally, infusion of CTZ resulted in significantly greater effects on amplitude in potentiated pathways as compared with control pathways. The interaction between LTP and CTZ was also obtained in a separate set of experiments in which GABA receptor antagonists were used to block inhibitory postsynaptic currents. Additionally, there was no significant change in paired-pulse facilitation in the presence of CTZ, indicating that presynaptic effects of the drug were negligible. These findings provide new evidence that LTP modifies AMPA receptor kinetics. Candidates for the changes responsible for the observed effects of LTP were evaluated using a model of AMPA receptor kinetics; a simple increase in the channel opening rate provided the most satisfactory match with the LTP data.

Sleep Deprivation Impairs Long-Term Potentiation in Rat Hippocampal Slices

2002 ◽  
Vol 88 (2) ◽  
pp. 1073-1076 ◽  
Author(s):  
I. G. Campbell ◽  
M. J. Guinan ◽  
J. M. Horowitz
Keyword(s):  
Sleep Deprivation ◽  
Neural Plasticity ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Adult Rats ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Population Spike Amplitude ◽  
Specific Factors

To determine if 12-h sleep deprivation disrupts neural plasticity, we compared long-term potentiation (LTP) in five sleep-deprived and five control rats. Thirty minutes after tetanus population spike amplitude increased 101 ± 15% in 16 slices from sleep deprived rats and 139 ± 14% in 14 slices from control rats. This significant ( P < 0.05) reduction of LTP, the first demonstration that the sleep deprivation protocol impairs plasticity in adult rats, may be due to several factors. Reduced LTP may indicate that sleep provides a period of recuperation for cellular processes underlying neural plasticity. Alternatively, the stress of sleep deprivation, as indicated by elevated blood corticosterone levels, or other non-sleep-specific factors of deprivation may contribute to the LTP reduction.

Prenatal Dietary Choline Supplementation Decreases the Threshold for Induction of Long-Term Potentiation in Young Adult Rats

1998 ◽  
Vol 79 (4) ◽  
pp. 1790-1796 ◽  
Author(s):  
Gowri K. Pyapali ◽  
Dennis A. Turner ◽  
Christina L. Williams ◽  
Warren H. Meck ◽  
H. Scott Swartzwelder
Keyword(s):  
Young Adult ◽  
Hippocampal Slices ◽  
Threshold Level ◽  
Long Term Potentiation ◽  
Adult Rats ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
Dietary Choline ◽  
Theta Burst

Pyapali, Gowri K., Dennis A. Turner, Christina L. Williams, Warren H. Meck, and H. Scott Swartzwelder. Prenatal dietary choline supplementation decreases the threshold for induction of long-term potentiation in young adult rats. J. Neurophysiol. 79: 1790–1796, 1998. Choline supplementation during gestation in rats leads to augmentation of spatial memory in adulthood. We hypothesized that prenatal (E12–E17) choline supplementation in the rat would lead to an enhancement of hippocampal synaptic plasticity as assessed by long-term potentiation (LTP) at 3–4 mo of age. LTP was assessed blindly in area CA1 of hippocampal slices with first suprathreshold (above threshold for LTP generation in control slices) theta-burst stimulus trains. The magnitude of potentiation after these stimuli was not different between slices from control and prenatally choline supplemented animals. Next, threshold (reliably leading to LTP generation in control slices) or subthreshold theta-burst stimulus trains were applied to slices from control, prenatally choline-supplemented, and prenatally choline-deprived rats. Threshold level stimulus trains induced LTP in slices from both the control and choline-supplemented rats but not in those from the choline-deficient rats. Subthreshold stimulus trains led to LTP induction in slices from prenatally choline-supplemented rats only. These observations indicate that prenatal dietary manipulation of the amino acid, choline, leads to subsequent significant alterations of LTP induction threshold in adult animals.

Effects of arsenite on long-term potentiation in hippocampal slices from young and adult rats

2006 ◽  
Vol 165 (2) ◽  
pp. 167-173 ◽  
Author(s):  
Katharina Krüger ◽  
Norbert Binding ◽  
Heidrun Straub ◽  
Ulrich Mußhoff
Keyword(s):  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Adult Rats ◽  
Term Potentiation

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 Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons

2012 ◽  
Vol 107 (4) ◽  
pp. 1058-1066 ◽  
Author(s):  
Peng Zhang ◽  
John E. Lisman
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Ca1 Neurons ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Term Potentiation ◽  
Activity Dependent

CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.

Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome release

2018 ◽  
Vol 119 (1) ◽  
pp. 305-311 ◽  
Author(s):  
Wei Chen ◽  
Yijun Guo ◽  
Wenjin Yang ◽  
Lei Chen ◽  
Dabin Ren ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junction ◽  
Connexin 43 ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Cx43 Expression ◽  
Term Potentiation ◽  
Junction Protein

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using Western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results imply that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release. NEW & NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that both phosphorylated connexin 43 (p-Cx43) expression and exosome release were elevated in the hippocampus following TBI. The promoted exosome release depends on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome treatment could partially restore the attenuated long-term potentiation. Our results provide new insight for future therapeutic direction on the functional recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the gap junction-mediated bystander effect.

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