21 results on '"long-term depression (LTD)"'
Search Results
2. Early life stress alters synaptic modification range in the rat lateral amygdala.
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Danielewicz, Joanna and Hess, Grzegorz
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PSYCHOLOGICAL stress , *AMYGDALOID body , *LONG-term synaptic depression , *LONG-term potentiation , *NEUROPLASTICITY , *THETA rhythm - Abstract
Highlights: [•] Saturating levels of LTP and LTD were induced in slices of the lateral amygdala. [•] Maximum LTP and LTD determine the extent of the synaptic modification range. [•] Maternal separation stress shrank the modification range in the thalamic input. [•] Maternal separation enhanced LTD in the cortical input. [•] Altered synaptic plasticity will have consequences for amygdala-dependent learning. [ABSTRACT FROM AUTHOR]
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- 2014
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3. The impairment in spatial learning and hippocampal LTD induced through the PKA pathway in juvenile-onset diabetes rats are rescued by modulating NMDA receptor function.
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Sacai, Hiroaki, Sasaki-Hamada, Sachie, Sugiyama, Azusa, Saitoh, Akiyoshi, Mori, Kazuhiro, Yamada, Mitsuhiko, and Oka, Jun-Ichiro
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HIPPOCAMPUS (Brain) , *DIABETES , *LABORATORY rats , *MENTAL depression , *METHYL aspartate receptors , *POSTSYNAPTIC potential - Abstract
Highlights: [•] Memantine rescued hippocampal-dependent memory and hippocampal LTD in JDM rats. [•] LTD was impaired by a malfunction in NR2B-containing NMDA receptors in JDM rats. [•] Abnormal NMDA receptor function was caused by excessive PKA activity in JDM rats. [Copyright &y& Elsevier]
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- 2014
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4. Social isolation stress reduces hippocampal long-term potentiation: Effect of animal strain and involvement of glucocorticoid receptors.
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Kamal, A., Ramakers, G.M.J., Altinbilek, B., and Kas, M.J.H.
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SOCIAL isolation , *PSYCHOLOGICAL stress , *HIPPOCAMPUS (Brain) , *LONG-term potentiation , *GLUCOCORTICOID receptors , *CORTICOSTERONE - Abstract
Highlights: [•] Long-term potentiation was measured in hippocampal slices from two mouse strains. [•] The level of long-term potentiation is different in one strain than the other. [•] Social isolation stress reduces long-term potentiation expression in both strains. [•] Corticosterone levels increase after social stress isolation. [•] Long-term potentiation was restored by glucocorticoid receptor antagonist. [ABSTRACT FROM AUTHOR]
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- 2014
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5. Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway.
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Forrest, C.M., Khalil, O.S., Pisar, M., McNair, K., Kornisiuk, E., Snitcofsky, M., Gonzalez, N., Jerusalinsky, D., Darlington, L.G., and Stone, T.W.
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NEURAL transmission , *GENE expression , *KYNURENINE , *DRUG administration , *CEREBROSPINAL fluid , *CYCLOOXYGENASE 2 , *LABORATORY rats - Abstract
Highlights: [•] An inhibitor of kynurenine-3-monoxygenase was administered to pregnant female rats. [•] Adult offspring at postnatal day 60 (P60) showed alterations in synaptic plasticity. [•] Expression of GluN2A, sonic hedgehog and other developmental proteins was changed. [•] Most earlier protein changes had disappeared with no changes in RNA or learning tasks. [•] Prenatal kynurenine pathway inhibition produces persistent synaptic and protein changes. [Copyright &y& Elsevier]
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- 2013
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6. Bidirectional modulation of hippocampal gamma (20–80Hz) frequency activity in vitro via alpha(α)- and beta(β)-adrenergic receptors (AR).
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Haggerty, D.C., Glykos, V., Adams, N.E., and LeBeau, F.E.N.
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HIPPOCAMPUS physiology , *ALPHA adrenoceptors , *BETA adrenoceptors , *NEURAL circuitry , *BRAIN waves , *EXCITATORY postsynaptic potential , *INHIBITORY postsynaptic potential - Abstract
Highlights: [•] Noradrenaline causes a reduction in gamma frequency oscillations in the hippocampus in vitro. [•] Noradrenaline causes a reduction in IPSPs and EPSPs during gamma frequency activity. [•] Activation of alpha-adrenergic 1 receptors reduces gamma frequency activity. [•] Activation of beta-adrenergic 1 receptors increases gamma frequency activity. [•] Noradrenaline can bidirectionally modulate network gamma oscillations via activation of different receptor subtypes. [ABSTRACT FROM AUTHOR]
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- 2013
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7. Patterned high-frequency stimulation induces a form of long-term depression dependent on GABAA and mACh receptors in the hippocampus.
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Zhu, Y.-Y., Jing, L., Duan, T.-T., Yuan, Q., Cao, J., Zhou, Q.-X., and Xu, L.
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BRAIN stimulation , *LONG-term care facilities , *MENTAL depression , *GABA receptors , *CHOLINERGIC receptors , *HIPPOCAMPUS physiology , *LONG-term potentiation - Abstract
Highlights: [•] A short patterned high-frequency stimulation (PHS) induces LTD in hippocampus. [•] PHS-induced LTD depends on both GABAARs and mAChRs but not NMDAR or mGluR activation. [•] PHS-induced LTD requires AMPAR endocytosis and protein synthesis. [ABSTRACT FROM AUTHOR]
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- 2013
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8. Modulation of synaptic plasticity by the coactivation of spatially distinct synaptic inputs in rat hippocampal CA1 apical dendrites.
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Kondo, Masashi, Kitajima, Tatsuo, Fujii, Satoshi, Tsukada, Minoru, and Aihara, Takeshi
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NEUROPLASTICITY , *HIPPOCAMPUS (Brain) , *DENDRITES , *NEURAL transmission , *AVERSIVE stimuli , *NEURAL circuitry , *LABORATORY rats - Abstract
Abstract: The phenomenon whereby the relative timing between presynaptic and postsynaptic spiking determines the direction and extent of synaptic changes in a critical temporal window is known as spike timing-dependent synaptic plasticity (STDP). We have previously reported that STDP profiles can be classified into two types depending on their layer-specific location along CA1 pyramidal neuron dendrites in the rat hippocampus, suggesting that there are differences in information processing between the proximal dendrite (PD) and distal dendrite (DD). However, how the different types of information processing interact at different dendritic locations remains unclear. To investigate how the temporal information of inputs to PD influences information processing at DD, PD stimulation was applied while the STDP protocol was simultaneously applied at DDs of CA1 pyramidal neurons. Synaptic plasticity induced by the STDP protocol at DDs was enhanced or depressed depending on the timing of the back-propagating action potentials (bAPs) and the excitatory and inhibitory postsynaptic potentials elicited by PD stimulation. These results suggested that bAPs function as carriers of temporal information of PD inputs to DD. Next, the influence of DD on PD was investigated using the same protocol. Synaptic plasticity at PD was modulated only if the pairing stimuli were applied to elicit coincidental timing of bAP and the excitatory postsynaptic potential. Such coding modulations could provide the basis for a novel learning rule and may be important factors in the integration of spatiotemporal input information in neural networks in the brain. [Copyright &y& Elsevier]
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- 2013
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9. Opposite long-term synaptic effects of 17β-estradiol and 5α-dihydrotestosterone and localization of their receptors in the medial vestibular nucleus of rats.
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Grassi, Silvarosa, Scarduzio, Mariangela, Panichi, Roberto, Dall’Aglio, Cecilia, Boiti, Cristiano, and Pettorossi, Vito E.
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ESTRADIOL , *STANOLONE , *VESTIBULAR nuclei , *ESTROGEN receptors , *ANDROGEN receptors , *AROMATASE - Abstract
Highlights: [•] E2 induces LTP and DHT LTD in single neurons of the medial vestibular nucleus (MVN). [•] MVN neurons are immunoreactive for oestrogen (ERα and ERβ) and androgen receptors (AR). [•] Many MVN neurons co-localize ERβ and AR and are immunoreactive for P-450 aromatase. [ABSTRACT FROM AUTHOR]
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- 2013
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10. Orexins/hypocretins cause sharp wave- and θ-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling
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Selbach, O., Doreulee, N., Bohla, C., Eriksson, K.S., Sergeeva, O.A., Poelchen, W., Brown, R.E., and Haas, H.L.
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CEREBROSPINAL fluid , *NERVOUS system , *CHOLINERGIC receptors , *WEIGHT gain , *BODY weight - Abstract
Orexins (OX), also called hypocretins, are bioactive peptides secreted from glucose-sensitive neurons in the lateral hypothalamus linking appetite, arousal and neuroendocrine-autonomic control. Here, OX-A was found to cause a slow-onset long-term potentiation of synaptic transmission (LTPOX) in the hippocampus of young adult mice. LTPOX was induced at Schaffer collateral-CA1 but not mossy fiber-CA3 synapses, and required transient sharp wave-concurrent population field-burst activity generated by the autoassociative CA3 network. Exogenous long θ-frequency stimulation of Schaffer collateral axons erased LTPOX in intact hippocampal slices but not mini slices devoid of the CA3 region. Pharmacological analysis revealed that LTPOX requires co-activation of ionotropic and metabotropic glutamatergic, GABAergic, as well as noradrenergic and cholinergic receptors. Together these data indicate that OX-A induces a state-dependent metaplasticity in the CA1 region associated with sharp-wave and θ rhythm activity as well as glutamatergic, GABAergic, aminergic, and cholinergic transmission. Thus, orexins not only regulate arousal threshold and body weight but also threshold and weight of synaptic connectivity, providing a molecular prerequisite for homeostatic and behavioral state-dependent control of neuronal plasticity and presumably memory functions. [Copyright &y& Elsevier]
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- 2004
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11. Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration
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Thompson, A.M., Swant, J., Gosnell, B.A., and Wagner, J.J.
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HIPPOCAMPUS (Brain) , *COCAINE , *LIMBIC system , *LOCAL anesthetics - Abstract
Long-lasting neuroadaptations that occur during drug use and remain after withdrawal are thought to contribute to the persisting and compulsive nature of drug addiction and relapse. At the molecular and cellular levels, mechanisms that have been implicated in the normal process of memory formation are increasingly being identified as potential contributors to the persistence of the addicted state. To investigate the effect of cocaine self-administration on synaptic plasticity, rats were allowed to self-administer 0.5 mg/kg/infusion cocaine or 0.9% NaCl during 90 min sessions for 15 consecutive days. These cocaine and saline self-administration subjects were then restricted to their home cages for 3, 30, or 100 days (3, 30, and 100 day cocaine/saline withdrawal groups) before the assessment of the induction and reversal of long-term potentiation (LTP) in the CA1 region of hippocampal slices. The magnitude of LTP was increased in the 3-day cocaine withdrawal group as compared with the 3-day saline withdrawal group, but this effect was short lived, as the 30-day cocaine and saline withdrawal groups exhibited similar LTP magnitudes. Interestingly, LTP was significantly decreased in the 100-day cocaine withdrawal group compared with the 100-day saline withdrawal group. These results support the hypothesis that the capacity for LTP is persistently altered after withdrawal from exposure to an addictive substance. In addition, this alteration can be differentially expressed such that depending upon the duration of the withdrawal period following the last drug exposure, LTP may be enhanced, unchanged, or suppressed. [Copyright &y& Elsevier]
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- 2004
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12. Subthreshold contribution of N-methyl-d-aspartate receptors to long-term potentiation induced by low-frequency pairing in rat hippocampal CA1 pyramidal cells
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Krasteniakov, N.V., Martina, M., and Bergeron, R.
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HIPPOCAMPUS (Brain) , *SOMATIC cells , *AMINO acids , *MATERIAL plasticity - Abstract
Long-term potentiation (LTP) is a use-dependent and persistent enhancement of synaptic strength. In the CA1 region of the hippocampus, LTP has Hebbian characteristics and requires precisely timed interaction between presynaptic firing and postsynaptic depolarization. Although depolarization is an absolute requirement for plasticity, it is still not clear whether the postsynaptic response during LTP induction should be subthreshold or suprathreshold for the generation of somatic action potential. Here, we use the whole-cell patch-clamp technique and different pairing protocols to examine systematically the postsynaptic induction requirements for LTP. We induce LTP by changes only in membrane potential while keeping the afferent stimulation constant and at minimal levels. This approach permits differentiation of two types of LTP: LTP induced with suprathreshold synaptic responses (LTPAP) and LTP induced with subthreshold excitatory postsynaptic current (EPSCs; LTPEPSC). We found that LTPAP (>40%) required pairing of depolarization (Vm≥-40 mV, for 40–60 s) with four to six (0.1 Hz) single synaptically initiated action potentials. LTPEPSC was of smaller magnitude (<30%) and required pairing of depolarization to -50 mV (60 s) with six subthreshold EPSCs. The N-methyl-d-aspartate receptor (NMDAR) antagonists aminophosphonovaleric acid and 7-chlorokynurenic acid consistently blocked LTPEPSC but were ineffective in preventing LTPAP. Robust, NMDAR-independent LTP is obtained by stronger postsynaptic depolarization that converts the EPSCs to suprathreshold somatic action potentials. Purely NMDAR-dependent LTP is obtained by pairing mild somatic depolarization with subthreshold afferent pulses to the postsynaptic cell. Our results indicate that the degree of postsynaptic depolarization in the presence of single afferent pulses determines the type and magnitude of LTP. [Copyright &y& Elsevier]
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- 2004
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13. Bidirectional shift in the cornu ammonis 3 pyramidal dendritic organization following brief stress
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Kole, M.H.P., Costoli, T., Koolhaas, J.M., and Fuchs, E.
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HIPPOCAMPUS (Brain) , *PHYSIOLOGICAL stress , *NEURONS , *RATS - Abstract
The negative impact of chronic stress at the structure of apical dendrite branches of cornu ammonis 3 (CA3) pyramidal neurons is well established. However, there is no information available on the CA3 dendritic organization related to short-lasting stress, which suffices to produce long-term habituation or sensitization of anxiety behaviors and neuroendocrine responses. Here, we tested the effects evoked by brief stress on the arrangements of CA3 pyramidal neuron dendrites, and the activity-dependent properties of the commissural-associational (C/A) excitatory postsynaptic potentials (EPSPs). Adult male rats were socially defeated followed by 3 weeks without further treatment or as comparison exposed to a regimen of a social defeat every second day for the same time period. We assessed CA3 pyramidal neurons with somatic whole-cell recording and neurobiotin application in acute hippocampal slices. The results from morphometric analysis of post hoc reconstructions demonstrated that CA3 dendrites from repeatedly stressed rats were reduced in surface area and length selectively at the apical cone (70% of control, approximately 280 μm from the soma). Brief stress, however, produced a similar decrease in apical dendritic length (77% of control, approximately 400 μm from the soma), accompanied by an increased length (167% of control) and branch complexity at the basal cone. The structural changes of the dendrites significantly influenced signal propagation by shortening the onset latency of EPSPs and increasing input resistance (r=0.45, P<0.01), of which the first was significantly changed in repeatedly stressed animals. Both brief and repeated stress long-lastingly impaired long-term potentiation of C/A synapses to a similar degree (P<0.05). These data indicate that the geometric plasticity of CA3 dendrites is dissociated from repetition of aversive experiences. A double social conflict suffices to drive a dynamic reorganization, by site-selective elimination and de novo growth of dendrite branches over the course of weeks after the actual experience. [Copyright &y& Elsevier]
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- 2004
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14. Dissection of tumor-necrosis factor-α inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early—but not late—phase LTP
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Butler, M. P., O'Connor, J. J., and Moynagh, P. N.
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INFLAMMATION , *CYTOKINES , *TUMOR necrosis factors , *NEUROLOGICAL disorders - Abstract
The pro-inflammatory cytokine tumor-necrosis factor-α (TNF-α) is elevated in several neuropathological states that are associated with learning and memory deficits. Previous work has reported that TNF-α inhibits the induction of LTP in areas CA1 [Neurosci Lett 146 (1992) 176] and dentate gyrus [Neurosci Lett 203 (1996) 17]. The mechanism(s) underlying this process of inhibition have not to date been addressed. Here, we show that perfusion of TNF-α prior to long-term potentiation (LTP) inducing stimuli inhibited LTP, and that in late-LTP (3 h post-tetanus) a depression in synaptic field recordings was observed (68±5%, n=6 versus control 175±7%, n=6, P<0.001). We investigated the involvement of the mitogen-activated protein kinase (MAPK) p38 in the inhibition of LTP by TNF-α as p38 MAPK has previously been shown to be involved in interleukin-1β inhibition of LTP in the dentate gyrus [Neuroscience 93 (1999b) 57]. Perfusion of TNF-α led to an increase in the levels of phosphorylated p38 MAPK detectable in the granule cells of the dentate gyrus. The p38 MAPK inhibitor SB 203580 (1 μM) was found by itself to have no significant effect on either early or late phase LTP in the dentate gyrus. SB 203580 was found to significantly reverse the inhibition of early LTP by TNF-α (SB/TNF-α 174±5%, n=6 versus TNF-α 120±7%, n=6, P<0.001, 1 h post-tetanus) to values comparable to control LTP (control 175±7%, n=6). Interestingly however, the depressive effects of TNF-α on late LTP (2–3 h) were clearly not attenuated by p38 MAPK inhibition (SB/TNF-α 132±5%, n=6 versus control LTP 175±7%, n=6, P<0.001, 3 h post-tetanus). This work suggests that TNF-α inhibition of LTP represents a biphasic response, a p38 MAPK-dependent phase that coincides with the early phase of LTP and a p38 MAPK independent phase that temporally maps to late LTP. [Copyright &y& Elsevier]
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- 2004
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15. A role for monomeric G-proteins in synaptic plasticity in the rat dentate gyrus in vitro
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Murray, Hilary J. and O'Connor, John J.
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GLYCOPROTEINS , *PHYSIOLOGICAL control systems , *BIOMOLECULES , *CLOSTRIDIUM - Abstract
Recent studies have implicated Ras signalling in synaptic plasticity. In this study we have investigated a role for the low molecular weight G proteins Ras, Rap, Ra1 and Rac in long-term potentiation and depression using Clostridium Sordelli Lethal Toxin-82 (LT-82), which inactivates Ras, Rap, Ra1 and Rac, and manumycin A, a Ras inhibitor. Perfusion of hippocampal slices with LT-82 (200 ng/ml) attenuated LTP (83±10%, n=5, P<0.01, compared with controls of 160±11% at 60 min post HFS, n=5). LT-82 had no effect on LTD (63±1% at 100 ng/ml, n=5 and 66±1% at 200 ng/ml, n=4, compared to controls of 56±6%, n=6). Manumycin A (2μM) had no effect on LTP (162±2%, n=5, compared to controls of 167±13%, n=5), but significantly attenuated LTD (88±6%, n=5, P<0.01, compared to controls of 63±9%, n=7). LT-82 (200 ng/ml) significantly increased the amplitude of the isolated NMDA-EPSP at 60 min post-drug application (240±40%, n=5, P<0.01, compared with controls of 100±4%, n=5). However, manumycin A, had no significant effect on NMDAR-EPSP amplitude (92±2%, n=5, compared with controls). These results demonstrate an important role for Ras in LTD and a role for Rap, Ra1 and Rac in LTP. [Copyright &y& Elsevier]
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- 2004
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16. Modulation of AMPA receptor kinetics differentially influences synaptic plasticity in the hippocampus
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Arai, A. C., Xia, Y.-F., and Suzuki, E.
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PROPIONIC acid , *SYNAPSES , *MEMORY , *NEUROLOGY - Abstract
Prior studies showed that positive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulators facilitate long-term potentiation (LTP) and improve the formation of several types of memory in animals and humans. However, these modulators are highly diverse in their effects on receptor kinetics and synaptic transmission and thus may differ also in their efficacy to promote changes in synaptic strength. The present study examined three of these modulators for their effects on synaptic plasticity in field CA1 of hippocampal slices, two of them being the benzamide drugs 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516) and 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine (CX546) which prominently enhance synaptic transmission yet differ in their relative impact on amplitude versus duration of the synaptic response. The third drug was cyclothiazide which potently blocks AMPA receptor desensitization. Effects on plasticity were assessed by measuring (i) the likelihood of obtaining stable potentiation when using theta-burst stimulation with three instead of four pulses per burst, (ii) the maximum amount of potentiation under optimal stimulation conditions, and (iii) the effect on long-term depression (LTD). Both benzamides facilitated the formation of stable potentiation induced with three-pulse burst stimulation which is normally ineffective. CX546 in addition increased maximally inducible potentiation after four-pulse burst stimulation from about 50% to 100%. Burst response analysis revealed that CX546 greatly prolonged the duration of depolarization by slowing the decay of the response which thus presumably leads to a more continuous N-methyl-d-aspartate (NMDA) receptor activation. Cyclothiazide was ineffective in increasing maximal potentiation in either field or whole-cell recordings. CX546, but not CX516, also enhanced nearly two-fold the NMDA receptor-dependent long-term depression induced by heterosynaptic 2 Hz stimulation. Tests with recombinant NMDA receptors (NR1/NR2A) showed that CX516 and CX546 have no direct effects on currents mediated by these receptors. These results suggest that (1) modulation of AMPA receptors which increases either response amplitude or duration can facilitate LTP formation, (2) modulators that effectively slow response deactivation augment the maximum magnitude of LTP and LTD, and (3) receptor desensitization may have a minor impact on synaptic plasticity in the hippocampus.Taken together, our data indicate that AMPA receptor modulators differ substantially in their ability to enhance synaptic potentiation or depression, depending on their particular influence on receptor kinetics, and hence that they may also be differentially effective in influencing higher-order processes such as memory encoding. [Copyright &y& Elsevier]
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- 2004
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17. Long-term regulation of n-methyl-d-aspartate receptor subunits and associated synaptic proteins following hippocampal synaptic plasticity
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Williams, J.M., Guévremont, D., Kennard, J.T.T., Mason-Parker, S.E., Tate, W.P., and Abraham, W.C.
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NEUROPLASTICITY , *METHYL aspartate - Abstract
Synaptic plasticity in the dentate gyrus is dependent on activation of the N-methyl-d-aspartate (NMDA)-subtype of glutamate receptors. In this study, we show that synaptic plasticity in turn regulates NMDA receptors, since subunits of the NMDA receptor complex are bidirectionally and independently regulated in the dentate gyrus following activation of perforant synapses in awake animals. Low-frequency stimulation that produced a mild synaptic depression resulted in a decrease in the NMDA receptor subunits NR1 and NR2B 48 h following stimulation. High-frequency stimulation that produced long-term potentiation resulted in an increase in NR1 and NR2B at the same time point. Further investigations revealed that in contrast to NR2B, NR1 levels increased gradually after long-term potentiation induction, reaching a peak level at 48 h, and were insensitive to the competitive NMDA receptor antagonist 3-3(2-carboxypiperazin-4-yl) propyl-1-phosphate. The increased levels of NR1 and NR2B at 48 h were found associated with synaptic membranes and with increased NMDA receptor-associated proteins, postsynaptic density protein 95, neuronal nitric oxide synthase and Ca2+/calmodulin-dependent protein kinase II, α subunit. These data suggest that the persistence of long-term potentiation is associated with an increase in the number of NMDA receptor complexes, which may be indicative of an increase in synaptic contact area. [Copyright &y& Elsevier]
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- 2003
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18. Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats
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Kamal, A., Artola, A., Biessels, G.J., Gispen, W.H., and Ramakers, G.M.J.
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HIPPOCAMPUS (Brain) , *DIABETES - Abstract
Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as “accelerated brain aging.”In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called “spike broadening.” The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca2+ spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca2+ influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging. [Copyright &y& Elsevier]
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- 2003
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19. Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY93→ALA) mutation
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Geracitano, R., Paolucci, E., Prisco, S., Guatteo, E., Zona, C., Longone, P., Ammassari-Teule, M., Bernardi, G., Berretta, N., and Mercuri, N.B.
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AMYOTROPHIC lateral sclerosis , *CEREBROSPINAL fluid , *ANALYSIS of variance - Abstract
Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly93→Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A−/SOD1−) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D2 dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS. [Copyright &y& Elsevier]
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- 2003
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20. A role for c-jun n-terminal kinase in the inhibition of long-term potentiation by interleukin-1β and long-term depression in the rat dentate gyrus in vitro
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Curran, B.P., Murray, H.J., and O’Connor, J.J.
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PROTEIN kinases , *CYTOKINES , *CEREBROSPINAL fluid - Abstract
Recent evidence has emphasised the importance of mitogen-activated protein kinase activation in the modulation of hippocampal synaptic plasticity. Whilst extracellular-regulated kinase activation is now regarded as a critical step in the induction of long-term potentiation (LTP), activation of p38 and c-Jun N-terminal kinase (JNK) is associated with its inhibition. Here, the effects of the novel JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-1 (SP600125) were investigated on the inhibition of LTP by cytokines interleukin-1β, interleukin-18 and tumour necrosis factor-α in the dentate gyrus. Perfusion of SP600125 alone prior to tetanic stimulation of the medial perforant path did not significantly affect baseline synaptic transmission, post-tetanic potentiation or the magnitude of induced LTP. When SP600125 was perfused onto slices prior to application of cytokines, this resulted in a complete reversal of the cytokine-mediated inhibition of LTP. Moreover, the magnitude of LTP attained in these slices was significantly greater than that obtained in vehicle control slices. Next, we investigated the effects of the JNK inhibitor on the impairment of pharmacologically isolated N-methyl-D-aspartate receptor-mediated potentials (NMDA-EPSPs) by interleukin-18. Whilst not affecting baseline amplitude when perfused alone, prior perfusion of SP600125 alleviated the depressive effect of interleukin-18 on NMDA-EPSPs. Finally, we examined the possibility of JNK involvement in the induction of long-term depression (LTD) in the dentate gyrus. Perfusion of SP600125 prior to low-frequency stimulation of the perforant path resulted in a significant attenuation of induced LTD, which suggests that JNK activation is a critical mediator of LTD in the dentate gyrus.These results directly implicate, for the first time, differential activation of JNK in the modulation of distinct forms of hippocampal synaptic plasticity. Whereas acute over-activation of JNK by pathophysiological concentrations of cytokines is detrimental to LTP, physiologic activation of JNK appears necessary for the induction of LTD. [Copyright &y& Elsevier]
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- 2003
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21. Effects of clozapine, haloperidol and iloperidone on neurotransmission and synaptic plasticity in prefrontal cortex and their accumulation in brain tissue: an in vitro study
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Gemperle, A.Y., Enz, A., Pozza, M.F., Lthi, A., and Olpe, H.R.
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CLOZAPINE , *PREFRONTAL cortex , *ANALYSIS of variance - Abstract
The mode of action of the antipsychotic drugs clozapine, haloperidol and iloperidone was investigated in layer V of prefrontal cortex slices using extracellular field potential, intracellular sharp-electrode as well as whole-cell voltage clamp recording techniques. Intracellular investigations on a broad range of concentrations revealed that the typical neuroleptic haloperidol at higher concentrations significantly depressed the excitatory postsynaptic component induced by electrical stimulation of layer II. This was not seen with the atypical neuroleptics clozapine and iloperidone. None of the three compounds had any effect on the resting membrane potential, spike amplitude or input resistance at relevant concentrations. Synaptic plasticity was assessed by means of extracellular field potential recordings. Clozapine significantly facilitated the potentiation of synaptic transmission, whereas haloperidol and iloperidone showed no effects. In line with its facilitating effect on synaptic plasticity, it could be demonstrated by whole-cell voltage clamp recordings that clozapine increased N-methyl-D-aspartic acid receptor-mediated excitatory postsynaptic currents in the majority of prefrontal cortical neurones. These investigations were made with neuroleptic drugs applied to the bath in the micromolar concentration range in order to approach clinical brain concentrations that are reached after administration of therapeutic doses. The drug concentrations reached in the slices after the experiments were assessed by means of high-pressure liquid chromatography coupled with mass-spectrometric detection. Surprisingly, drug accumulation in the in vitro preparation was of similar degree as reported in vivo.In conclusion, the typical neuroleptic haloperidol significantly depressed excitatory synaptic transmission in layer V neurones of the prefrontal cortex. In contrast, the two atypical neuroleptics iloperidone and clozapine revealed no depressing effects. This feature of the atypical neuroleptics might be beneficial since a hypofunctionality of this brain area is thought to be linked with the pathophysiology of schizophrenia. Additionally, clozapine facilitated long-term potentiation, which might be linked with the clinically observed beneficial effects on certain cognitive parameters. The clozapine-induced increase of N-methyl-D-aspartic acid receptor-mediated currents suggests that clozapine facilitates the induction of long-term potentiation. Furthermore, the present study points to the importance of considering the significant accumulation of neuroleptic drugs in in vitro studies. [Copyright &y& Elsevier]
- Published
- 2003
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