Denise Manahan-Vaughan

Ruhr-Universität Bochum, Bochum, North Rhine-Westphalia, Germany

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Publications (105)490.43 Total impact

  • Jinzhong Jeremy Goh, Denise Manahan-Vaughan
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    ABSTRACT: Experience-dependent synaptic plasticity is widely expressed in the mammalian brain and is believed to underlie memory formation. Persistent forms of synaptic plasticity in the hippocampus, such as long-term potentiation (LTP) and long-term depression (LTD) are particularly of interest, as evidence is accumulating that they are expressed as a consequence of, or at the very least in association with, hippocampus-dependent novel learning events. Learning-facilitated plasticity describes the property of hippocampal synapses to express persistent synaptic plasticity when novel spatial learning is combined with afferent stimulation that is subthreshold for induction of changes in synaptic strength. In mice it occurs following novel object recognition and novel object-place recognition. Calmodulin-dependent kinase II (CAMKII) is strongly expressed in synapses and has been shown to be required for hippocampal LTP in vitro and for spatial learning in the water maze. Here, we show that in mice that undergo persistent inhibitory autophosphorylation of αCAMKII, object-place learning is intact. Furthermore, these animals demonstrate a higher threshold for induction of persistent (>24h) hippocampal LTP in the hippocampal CA1 region during unrestrained behaviour. The transgenic mice also express short-term depression in response to afferent stimulation frequencies that are ineffective in controls. Furthermore, they express stronger LTD in response to novel learning of spatial configurations compared to controls. These findings support that modulation of αCAMKII activity via autophosphorylation at the Thr305/306 site comprises a key mechanism for the maintenance of synaptic plasticity within a dynamic range. They also indicate that a functional differentiation occurs in the way spatial information is encoded: whereas LTP is likely to be critically involved in the encoding of space per se, LTD appears to play a special role in the encoding of the content or features of space.
    Behavioural brain research 01/2014; · 3.22 Impact Factor
  • Niels Hansen, Denise Manahan-Vaughan
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    ABSTRACT: Synaptic plasticity comprises a cellular mechanism through which the hippocampus most likely enables memory formation. Neuromodulation, related to arousal, is a key aspect in information storage. The activation of locus coeruleus (LC) neurons by novel experience leads to noradrenaline release in the hippocampus at the level of the dentate gyrus (DG). We explored whether synaptic plasticity in the DG is influenced by activation of the LC via electrical stimulation. Coupling of test-pulses that evoked stable basal synaptic transmission in the DG with stimulation of the LC induced β-adrenoreceptor-dependent long-term depression (LTD) at perforant path-DG synapses in adult rats. Furthermore, persistent LTD (>24 h) induced by perforant path stimulation also required activation of β-adrenergic receptors: Whereas a β-adrenergic receptor antagonist (propranolol) prevented, an agonist (isoproterenol) strengthened the persistence of LTD for over 24 h. These findings support the hypothesis that persistent LTD in the DG is modulated by β-adrenergic receptors. Furthermore, LC activation potently facilitates DG LTD. This suggests in turn that synaptic plasticity in the DG is tightly regulated by activity in the noradrenergic system. This may reflect the role of the LC in selecting salient information for subsequent synaptic processing in the hippocampus.
    Cerebral Cortex 01/2014; · 8.31 Impact Factor
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    ABSTRACT: Noncompetitive N-methyl-d-aspartate receptor antagonists such as phencyclidine and MK-801 are known to impair cognitive function in rodents and humans, and serve as a useful tool to study the cellular basis for pathogenesis of schizophrenia cognitive symptoms. In the present study, we tested in rats the effect of MK-801 on ventral hippocampus (HPC)-medial prefrontal cortex (mPFC) synaptic transmission and the performance in 2 cognitive tasks. We found that single injection of MK-801 (0.1 mg/kg) induced gradual and long-lasting increases of the HPC-mPFC response, which shares the common expression mechanisms with long-term potentiation (LTP). But unlike LTP, its induction required no enhanced or synchronized synaptic inputs, suggesting aberrant characteristics. In parallel, rats injected with MK-801 showed impairments of mPFC-dependent cognitive flexibility and HPC-mPFC pathway-dependent spatial working memory. The effects of MK-801 on HPC-mPFC responses and spatial working memory decayed in parallel within 24 h. Moreover, the therapeutically important subtype 2/3 metabotropic glutamate receptor agonist LY379268, which blocked MK-801-induced potentiation, ameliorated the MK-801-induced impairment of spatial working memory. Our results show a novel form of use-independent long-lasting potentiation in HPC-mPFC pathway induced by MK-801, which is associated with impairment of HPC-mPFC projection-dependent cognitive function.
    Cerebral Cortex 12/2013; · 8.31 Impact Factor
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    ABSTRACT: The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of memory depend on adequate hippocampal function. Extinction learning comprises active inhibition of no longer relevant learned information concurrent with suppression of a previously learned reaction. It is highly dependent on context, and evidence exists that it requires hippocampal activation. In this study we addressed whether context-based extinction as well as hippocampus-dependent tasks such as, object recognition and object-place recognition, are equally affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar rats were used. For the extinction study, animals learned that a particular floor context indicated that they should turn into one specific arm (e.g. left) to receive a food reward. On the day after reaching the learning criterion of 80% correct choices, the floor context was changed, no reward was given and animals were expected to extinguish the learned response. Both, young and older rats managed this first extinction trial in the new context with older rats showing a faster extinction performance. One day later, animals were returned to the T-maze with the original floor context and renewal effects were assessed. In this case, only young but not older rats showed the expected renewal effect (lower extinction ratio as compared to the day before). To assess general memory abilities, animals were tested in the standard object recognition and object-place memory tasks. Evaluations were made at 5 min, 1h and 7 day intervals. Object recognition memory was poor at short-term and intermediate time-points in older but not young rats. Object-place memory performance was unaffected at 5 min, but impaired at 1h in older but not young rats. Both groups were impaired at 7 days. These findings support that not only aspects of general memory, but also context-dependent extinction learning, are affected by moderate aging. This may reflect less flexibility in revising hard-wired knowledge or reduced adaptability to new learning challenges. © 2013 Wiley Periodicals, Inc.
    Hippocampus 10/2013; · 5.49 Impact Factor
  • Jinzhong Jeremy Goh, Denise Manahan-Vaughan
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    ABSTRACT: In the intact mouse hippocampus patterned afferent stimulation does not lead to long-term depression (LTD) at Schaffer collateral (Sc)-CA1 synapses, but the same synapses express robust LTD (<24 h) if test-pulse or patterned afferent experience is coupled with novel spatial learning. This suggests that the failure of sole afferent stimulation to elicit LTD relates to the absence of neuromodulatory input related to increased arousal or novelty during learning. Locus coeruleus (LC) firing increases during novel experience, and in rats patterned stimulation of the LC together with test-pulse stimulation of Sc-CA1 synapses leads to robust LTD in vivo. This effect is mediated by beta-adrenergic receptors. Here, we explored if activation of beta-adrenergic receptors supports the expression of LTD in freely behaving mice. We also explored if beta-adrenergic receptors contribute to endogenous LTD that is expressed following spatial learning. Patterned stimulation of Sc-CA1 synapses at 3 Hz (200 pulses) resulted in short-term depression (STD). Pretreatment with isoproterenol, an agonist of beta-adrenergic receptors, resulted in robust LTD (<24 h). Test-pulse stimulation under controls conditions elicited field potentials that were stable for the 24-h monitoring period. Coupling of test-pulses with a novel spatial object recognition task resulted in robust endogenous LTD (<24 h). Pretreatment with propranolol, a beta-adrenergic receptor antagonist, completely prevented endogenous LTD that was enabled by learning and prevented object recognition learning itself. These data indicate that the absence of LTD in freely behaving mice, under standard recording conditions, does not reflect an inability of mice to express LTD, rather it is due to the absence of an noradrenalin tonus. Our data also support that spatial object recognition requires beta-adrenergic receptor activation. Furthermore, LTD that is enabled by novel spatial learning critically depends on activation of beta-adrenergic receptors that are presumably activated by noradrenalin released by the LC in response to the novel experience. © 2013 Wiley Periodicals, Inc.
    Hippocampus 07/2013; · 5.49 Impact Factor
  • Marion Agnès Emma André, Denise Manahan-Vaughan
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    ABSTRACT: Recently, it has emerged that visual spatial exploration facilitates synaptic plasticity at different synapses within the trisynaptic network. Particularly striking is the finding that visuospatial contexts facilitate hippocampal long-term depression (LTD), raising the possibility that this form of plasticity may be important for memory formation. It is not known whether other sensory modalities elicit similar permissive effects on LTD. Here, we explored if spatial olfactory learning facilitates LTD in the hippocampus region of freely behaving rats rats. Patterned afferent stimulation of the Schaffer collaterals elicited short-term depression (STD) (<1h) of evoked responses in the Stratum radiatum of the CA1 region. Coupling of this protocol with novel exploration of a spatial constellation of olfactory cues facilitated short-term depression into LTD that lasted for over 24h. Facilitation of LTD did not occur when animals were re-exposed 1 week later to the same odors in the same spatial constellation. Evaluation of learning behavior revealed that 1 week after the 1(st) odor exposure, the animals remembered the odors. These data support that the hippocampus can use non-visuospatial resources, and specifically can use spatial olfactory information, to facilitate LTD and to generate spatial representations. The data also support that a tight relationship exists between the processing of spatial contextual information and the expression of LTD in the hippocampus. © 2013 Wiley Periodicals, Inc.
    Hippocampus 06/2013; · 5.49 Impact Factor
  • Anne Kemp, Wolfgang Tischmeyer, Denise Manahan-Vaughan
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    ABSTRACT: De novo gene transcription is a prerequisite for long-term information storage in the brain. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with long-lasting synaptic plasticity to the coupling of afferent stimulation with a spatial learning experience. Strikingly, long-term depression (LTD) is facilitated by context-dependent spatial learning experiences suggesting it may play a role in information storage to enable spatial memory. Here, we investigated if learning-facilitated LTD requires the transcription factor, c-Fos and is transcription-dependent. Novel spatial learning about object-place configurations coupled with weak low frequency afferent stimulation induced robust LTD in control animals that persisted for>24h and was associated with elevations in hippocampal expression of c-Fos. Intracerebral application of a c-fos antisense oligonucleotide prevented the facilitation of LTD by novel spatial learning, inhibited elevations of c-Fos triggered by LTD and impaired spatial learning. The expression of the transcription factor zif268 was unaffected by the c-fos antisense oligonucleotide. Learning-facilitated LTD was prevented by a transcription inhibitor. These data support that learning-facilitated LTD requires elevations in c-Fos and is transcription dependent. The observation that LTD shares key regulatory mechanisms with learning and memory processes argues strongly for a role for this form of synaptic plasticity in long-term information storage in the hippocampus.
    Behavioural brain research 04/2013; · 3.22 Impact Factor
  • Jana Kenney, Denise Manahan-Vaughan
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    ABSTRACT: The hippocampus may be functionally differentiated along its dorsoventral axis. In contrast to the wealth of data available on synaptic plasticity mechanisms in the dorsal hippocampus, little is known about synaptic plasticity processes in the intermediate hippocampus. Behavioural data suggest that this structure may play a distinct role in learning and memory. Here, we compared amplitudes, frequency-dependency and persistency of long-term potentiation (LTP) and long-term depression (LTD) in the dorsal (DDG) and intermediate dentate gyrus (IDG). In freely moving rats, high-frequency stimulation (HFS) at 200Hz (10 burst of 15 stimuli) elicited LTP of similar magnitude in both structures that persisted for over 24h. The intermediate dentate gyrus is more likely to exhibit persistent LTP than its dorsal counterpart, however: HFS at 200Hz (3 or 1 burst(s)) or 100Hz elicited short-term potentiation (STP) in DDG, unlike in the IDG, where LTP could be recorded for at least 4 hours. Whereas low frequency stimulation (LFS) at 1Hz elicited long-lasting LTD (>24h) in the DDG, it had no significant effect on fEPSP profile in the IDG. LFS at 2 Hz elicited short-term depression in DDG and had no effect in IDG. LTP in both IDG and DDG required activation of N-methyl-D-aspartate receptors. Paired-pulse and input-output responses differed in IDG and DDG. Our data suggest that afferent input from the entorhinal cortex generates a different response profile in the dorsal vs. intermediate DG, which may in turn relate to their postulated distinct roles in synaptic information processing and memory formation.
    Neuropharmacology 03/2013; · 4.11 Impact Factor
  • Valentina Wiescholleck, Denise Manahan-Vaughan
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    ABSTRACT: It is postulated that disruptions of glutamatergic signalling may underlie the pathophysiology of psychosis and schizophrenia. A strong body of evidence indicates that antagonism of the N-methyl-D-aspartate receptor (NMDAR) leads to similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans to those that have been identified to occur in psychosis. One of the main loci of change appears to comprise the hippocampus, raising the question as to whether changes in hippocampal glutamatergic transmission may drive changes in GABAergic and dopaminergic-mediated signalling in schizophreniform diseases. NMDAR antagonists such as MK801, PCP and ketamine all elicit similar psychosis-related effects, with MK801 inducing the most potent psychotomimetic reactions. Treatment with MK801 is associated with a loss of hippocampal synaptic plasticity, hippocampus-dependent learning and cognitive deficits. These findings have raised the question as to whether targeting the NMDA receptors or its modulators could prove an effective strategy in treatment of psychosis and schizophrenia. Specifically, the otherwise untreatable negative and cognitive symptoms of schizophrenia currently comprise the highest research priority. A single injection with MK801 has been used to emulate first-episode psychosis in animals. This treatment induces both, psychosis-related acute effects but interestingly also persisting consequences, which might be more sensitive as indicators of drug efficacy. Here, we review the current status of the field with regard to the MK801 animal model of first-episode psychosis and its relevance for the glutamate hypothesis of schizophrenia. Furthermore, we argue that synaptic plasticity may be a better assay for assessing novel schizophrenia therapeutics than behavioural evaluation.
    Neuropharmacology 01/2013; · 4.11 Impact Factor
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    Hardy Hagena, Denise Manahan-Vaughan
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    ABSTRACT: Long-term potentiation (LTP) and long-term depression (LTD) are two mechanisms involved in the long-term storage of information in hippocampal synapses. In the hippocampal CA1 region, the late phases of LTP and LTD are protein-synthesis dependent. In the dentate gyrus, late-LTP but not LTD requires protein synthesis. The protein synthesis-dependency of persistent plasticity at CA3 synapses has not yet been characterized. Here, the roles of protein transcription and translation at mossy fiber (mf) and associational/commissural (AC)- synapses were studied in freely behaving rats. In control animals, low-frequency stimulation (LFS) evoked robust LTD (>24 h), whereas high-frequency stimulation (HFS) elicited robust LTP (>24 h) at both mf-CA3 and AC-CA3 synapses. Translation inhibitors prevented early and late phases of LTP and LTD at mf-CA3 synapses. In contrast, at AC-CA3 synapses, translation inhibitors prevented intermediate/late-LTP and late-LTD only. Transcription effects were also synapse-specific: whereas transcription inhibitors inhibited late-LTP and late-LTD (>3 h) at mf-CA3 synapses, at AC-CA3 synapses, protein transcription affected early-LTP and late-LTD. These results show that the AC-CA3 and mf-CA3 synapses display different properties in terms of their protein synthesis dependency, suggesting different roles in the processing of short- and long term synaptic plasticity.
    Frontiers in Integrative Neuroscience 01/2013; 7:10.
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    Valentina Wiescholleck, Denise Manahan-Vaughan
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    ABSTRACT: Irreversible N-methyl-D-aspartate receptor (NMDAR) antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP) of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments. The ability to express LTP at the perforant pathway - dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3, and 4 weeks after a single treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue. Taken together, these data support that acute treatment with an irreversible NMDAR-antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.
    Frontiers in Integrative Neuroscience 01/2013; 7:12.
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    ABSTRACT: [This corrects the article on p. e51767 in vol. 7.].
    PLoS ONE 01/2013; 8(1). · 3.53 Impact Factor
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    Jana Kenney, Denise Manahan-Vaughan
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    ABSTRACT: The dorsoventral axis of the hippocampus is differentiated into dorsal, intermediate, and ventral parts. Whereas the dorsal part is believed to specialize in processing spatial information, the ventral may be equipped to process non-spatial information. The precise role of the intermediate hippocampus is unclear, although recent data suggests it is functionally distinct, at least from the dorsal hippocampus. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with robust synaptic plasticity (>24 h) when a spatial learning event is coupled with afferent stimulation that would normally not lead to a lasting plasticity response: in the dorsal hippocampus novel space facilitates robust expression of long-term potentiation (LTP), whereas novel spatial content facilitates long-term depression (LTD). We explored whether the intermediate hippocampus engages in this kind of synaptic plasticity in response to novel spatial experience. In freely moving rats, high-frequency stimulation at 200 Hz (3 bursts of 15 stimuli) elicited synaptic potentiation that lasted for at least 4 h. Coupling of this stimulation with the exploration of a novel holeboard resulted in LTP that lasted for over 24 h. Low frequency afferent stimulation (1 Hz, 900 pulses) resulted in short-term depression (STD) that was significantly enhanced and prolonged by exposure to a novel large orientational (landmark) cues, however LTD was not enabled. Exposure to a holeboard that included novel objects in the holeboard holes elicited a transient enhancement of STD of the population spike (PS) but not field EPSP, and also failed to facilitate the expression of LTD. Our data suggest that the intermediate dentate gyrus engages in processing of spatial information, but is functionally distinct to the dorsal dentate gyrus. This may in turn reflect their assumed different roles in synaptic information processing and memory formation.
    Frontiers in Synaptic Neuroscience 01/2013; 5:10.
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    Jinzhong J Goh, Denise Manahan-Vaughan
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    ABSTRACT: Persistent synaptic plasticity has been subjected to intense study in the decades since it was first described. Occurring in the form of long-term potentiation (LTP) and long-term depression (LTD), it shares many cellular and molecular properties with hippocampus-dependent forms of persistent memory. Recent reports of both LTP and LTD occurring endogenously under specific learning conditions provide further support that these forms of synaptic plasticity may comprise the cellular correlates of memory. Most studies of synaptic plasticity are performed using in vitro or in vivo preparations where patterned electrical stimulation of afferent fibers is implemented to induce changes in synaptic strength. This strategy has proven very effective in inducing LTP, even under in vivo conditions. LTD in vivo has proven more elusive: although LTD occurs endogenously under specific learning conditions in both rats and mice, its induction has not been successfully demonstrated with afferent electrical stimulation alone. In this study we screened a large spectrum of protocols that are known to induce LTD either in hippocampal slices or in the intact rat hippocampus, to clarify if LTD can be induced by sole afferent stimulation in the mouse CA1 region in vivo. Low frequency stimulation at 1, 2, 3, 5, 7, or 10 Hz given in the range of 100 through 1800 pulses produced, at best, short-term depression (STD) that lasted for up to 60 min. Varying the administration pattern of the stimuli (e.g., 900 pulses given twice at 5 min intervals), or changing the stimulation intensity did not improve the persistency of synaptic depression. LTD that lasts for at least 24 h occurs under learning conditions in mice. We conclude that a coincidence of factors, such as afferent activity together with neuromodulatory inputs, play a decisive role in the enablement of LTD under more naturalistic (e.g., learning) conditions.
    Frontiers in Integrative Neuroscience 01/2013; 7:1.
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    Ayla Aksoy-Aksel, Denise Manahan-Vaughan
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    ABSTRACT: In terms of its sub-regional differentiation, the hippocampal CA1 region receives cortical information directly via the perforant (temporoammonic) path (pp-CA1 synapse) and indirectly via the tri-synaptic pathway where the last relay station is the Schaffer collateral-CA1 synapse (Sc-CA1 synapse). Research to date on pp-CA1 synapses has been conducted predominantly in vitro and never in awake animals, but these studies hint that information processing at this synapse might be distinct to processing at the Sc-CA1 synapse. Here, we characterized synaptic properties and synaptic plasticity at the pp-CA1 synapse of freely behaving adult rats. We observed that field excitatory postsynaptic potentials at the pp-CA1 synapse have longer onset latencies and a shorter time-to-peak compared to the Sc-CA1 synapse. LTP (>24 h) was successfully evoked by tetanic afferent stimulation of pp-CA1 synapses. Low frequency stimulation evoked synaptic depression at Sc-CA1 synapses, but did not elicit LTD at pp-CA1 synapses unless the Schaffer collateral afferents to the CA1 region had been severed. Paired-pulse responses also showed significant differences. Our data suggest that synaptic plasticity at the pp-CA1 synapse is distinct from the Sc-CA1 synapse and that this may reflect its specific role in hippocampal information processing.
    Frontiers in Synaptic Neuroscience 01/2013; 5:5.
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    Niels Hansen, Denise Manahan-Vaughan
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    ABSTRACT: Dopamine (DA) plays an essential role in the enablement of cognition. It adds color to experience-dependent information storage, conferring salience to the memories that result. At the synaptic level, experience-dependent information storage is enabled by synaptic plasticity, and given its importance for memory formation, it is not surprising that DA comprises a key neuromodulator in the enablement of synaptic plasticity, and particularly of plasticity that persists for longer periods of time: Analogous to long-term memory. The hippocampus, that is a critical structure for the synaptic processing of semantic, episodic, spatial, and declarative memories, is specifically affected by DA, with the D1/D5 receptor proving crucial for hippocampus-dependent memory. Furthermore, D1/D5 receptors are pivotal in conferring the properties of novelty and reward to information being processed by the hippocampus. They also facilitate the expression of persistent forms of synaptic plasticity, and given reports that both long-term potentiation and long-term depression encode different aspects of spatial representations, this suggests that D1/D5 receptors can drive the nature and qualitative content of stored information in the hippocampus. In light of these observations, we propose that D1/D5 receptors gate hippocampal long-term plasticity and memory and are pivotal in conferring the properties of novelty and reward to information being processed by the hippocampus.
    Cerebral Cortex 11/2012; · 8.31 Impact Factor
  • Jinzhong Jeremy Goh, Denise Manahan-Vaughan
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    ABSTRACT: Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with persistent plasticity to afferent stimulation when coupled with a spatial learning event, whereby the afferent stimulation normally produces short-term plasticity or no change in synaptic strength if given in the absence of novel learning. Recently, it was reported that in the mouse hippocampus intrinsic long-term depression (LTD > 24 h) occurs when test-pulse afferent stimulation is coupled with a novel spatial learning. It is not known to what extent this phenomenon shares molecular properties with synaptic plasticity that is typically induced by means of patterned electrical afferent stimulation. In previous work, we showed that a novel spatial object recognition task facilitates LTD at the Schaffer collateral-CA1 synapse of freely behaving adult mice, whereas reexposure to the familiar spatial configuration ∼24 h later elicited no such facilitation. Here we report that treatment with the NMDA receptor antagonist, (±)-3-(2-Carboxypiperazin-4-yl)-propanephosphonic acid (CPP), or antagonism of metabotropic glutamate (mGlu) receptor, mGlu5, using 2-methyl-6-(phenylethynyl) pyridine (MPEP), completely prevented LTD under the novel learning conditions. Behavioral assessment during re-exposure after application of the antagonists revealed that the animals did not remember the object during novel exposure and treated them as if they were novel. Under these circumstances, where the acquisition of novel spatial information was involved, LTD was facilitated. Our data support that the endogenous LTD that is enabled through novel spatial learning in adult mice is critically dependent on the activation of both the NMDA receptors and mGlu5. © 2012 Wiley Periodicals, Inc.
    Hippocampus 09/2012; · 5.49 Impact Factor
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    Sreedeep Mukherjee, Denise Manahan-Vaughan
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    ABSTRACT: Storage and processing of information at the synaptic level is enabled by the ability of synapses to persistently alter their efficacy. This phenomenon, known as synaptic plasticity, is believed to underlie multiple forms of long-term memory in the mammalian brain. It has become apparent that the metabotropic glutamate (mGlu) receptor is critically required for both persistent forms of memory and persistent synaptic plasticity. Persistent forms of synaptic plasticity comprise long-term potentiation (LTP) and long-term depression (LTD) that last at least for 4 h but can be followed in vivo for days and weeks. These types of plasticity are believed to be analogous to forms of memory that persist for similar time-spans. The mGlu receptors are delineated into three distinct groups based on their G-protein coupling and agonist affinity and also exercise distinct roles in the way they regulate both long-term plasticity and long-term hippocampus-dependent memory. Here, the mGlu receptors will be reviewed both in general, and in the particular context of their role in persistent (>4 h) forms of hippocampus-dependent synaptic plasticity and memory, as well as forms of synaptic plasticity that have been shown to be directly regulated by memory events. This article is part of a Special Issue entitled 'mGluR'.
    Neuropharmacology 06/2012; · 4.11 Impact Factor
  • Arne Buschler, Jinzhong Jeremy Goh, Denise Manahan-Vaughan
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    ABSTRACT: Hippocampal synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) is likely to enable synaptic information storage in support of memory formation. The mouse brain has been subjected to intensive scrutiny in this regard; however, a multitude of studies has examined synaptic plasticity in the hippocampal slice preparation, whereas very few have addressed synaptic plasticity in the freely behaving mouse. Almost nothing is known about the frequency or N-methyl-D-aspartate receptor (NMDAR) dependency of hippocampal synaptic plasticity in the intact mouse brain. Therefore, in this study, we investigated the forms of synaptic plasticity that are elicited at different afferent stimulation frequencies. We also addressed the NMDAR dependency of this phenomenon. Adult male C57BL/6 mice were chronically implanted with a stimulating electrode into the Schaffer collaterals and a recording electrode into the Stratum radiatum of the CA1 region. To examine synaptic plasticity, we chose protocols that were previously shown to produce either LTP or LTD in the hippocampal slice preparation. Low-frequency stimulation (LFS) at 1 Hz (900 pulses) had no effect on evoked responses. LFS at 3 Hz (ranging from 200 up to 2 × 900 pulses) elicited short-term depression (STD, <45 min). LFS at 3 Hz (1,200 pulses) elicited slow-onset potentiation, high-frequency stimulation (HFS) at 100 Hz (100 or 200 pulses) or at 50 Hz was ineffective, whereas 100 Hz (50 pulses) elicited short-term potentiation (STP). HFS at 100 Hz given as 2 × 30, 2 × 50, or 4 × 50 pulses elicited LTP (>24 h). Theta-burst stimulation was ineffective. Antagonism of the NMDAR prevented STD, STP, and LTP. This study shows for the first time that protocols that effectively elicit persistent synaptic plasticity in the slice preparation elicit distinctly different effects in the intact mouse brain. Persistent LTD could not be elicited with any of the protocols tested. Plasticity responses are NMDAR dependent, suggesting that these phenomena are relevant for hippocampus-dependent learning. © 2012 Wiley Periodicals, Inc.
    Hippocampus 06/2012; · 5.49 Impact Factor
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    Jinzhong Jeremy Goh, Denise Manahan-Vaughan
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    ABSTRACT: Although synaptic plasticity is believed to comprise the cellular substrate for learning and memory, limited direct evidence exists that hippocampus-dependent learning actually triggers synaptic plasticity. It is likely, however, that long-term potentiation (LTP) works in concert with its counterpart, long-term depression (LTD) in the creation of spatial memory. It has been reported in rats that weak synaptic plasticity is facilitated into persistent plasticity if afferent stimulation is coupled with a novel spatial learning event. It is not known if this phenomenon also occurs in other species. We recorded from the hippocampal CA1 of freely behaving mice and observed that novel spatial learning triggers endogenous LTD. Specifically, we observed that LTD is enabled when test-pulse afferent stimulation is given during the learning of object constellations or during a spatial object recognition task. Intriguingly, LTP is significantly impaired by the same tasks, suggesting that LTD is the main cellular substrate for this type of learning. These data indicate that learning-facilitated plasticity is not exclusive to rats and that spatial learning leads to endogenous LTD in the hippocampus, suggesting an important role for this type of synaptic plasticity in the creation of hippocampus-dependent memory.
    Cerebral Cortex 04/2012; · 8.31 Impact Factor

Publication Stats

3k Citations
490.43 Total Impact Points

Institutions

  • 2004–2013
    • Ruhr-Universität Bochum
      • • Faculty of Medicine
      • • International Graduate School of Neuroscience
      Bochum, North Rhine-Westphalia, Germany
  • 1999–2008
    • Humboldt-Universität zu Berlin
      • Department of Biology
      Berlín, Berlin, Germany
  • 2000–2003
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 1998–1999
    • Leibniz Institute for Neurobiology
      • Department of Neurophysiology
      Magdeburg, Saxony-Anhalt, Germany