Hierarchical order of coexisting pre- and postsynaptic forms of long-term potentiation at synapses in amygdala

Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2010; 107(44):19073-8. DOI: 10.1073/pnas.1009803107
Source: PubMed

ABSTRACT Synaptic rules that may determine the interaction between coexisting forms of long-term potentiation (LTP) at glutamatergic central synapses remain unknown. Here, we show that two mechanistically distinct forms of LTP could be induced in thalamic input to the lateral nucleus of the amygdala (LA) with an identical presynaptic stimulation protocol, depending on the level of postsynaptic membrane polarization. One form of LTP, resulting from pairing of postsynaptic depolarization and low-frequency presynaptic stimulation, was both induced and expressed postsynaptically ("post-LTP"). The same stimulation in the absence of postsynaptic depolarization led to LTP, which was induced and expressed presynaptically ("pre-LTP"). The inducibility of coexisting pre- and postsynaptic forms of LTP at synapses in thalamic input followed a well-defined hierarchical order, such that pre-LTP was suppressed when post-LTP was induced. This interaction was mediated by activation of cannabinoid type 1 receptors by endogenous cannabinoids released in the lateral nucleus of the amygdala in response to activation of the type 1 metabotropic glutamate receptor. These results suggest a previously unknown mechanism by which the hierarchy of coexisting forms of long-term synaptic plasticity in the neural circuits of learned fear could be established, possibly reflecting the hierarchy of memories for the previously experienced fearful events according to their aversiveness level.

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    • ") Failure rate (Tsvetkov et al., 2002) PPR (Huang and Kandel, 1998; Tsvetkov et al., 2002; Humeau et al., 2003) MK801 blockade (Shaban et al., 2006) Thalamic-lateral amygdala synapse E LTP Failure rate (Shin et al., 2010b) PPR (Shin et al., 2010b) Inhibitory synapses in basolateral nucleus I eCB-LTDi, heterosynaptic Mini analysis (Azad et al., 2004) PPR (Marsicano et al., 2002) "
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    ABSTRACT: Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity.
    Frontiers in Synaptic Neuroscience 10/2013; 5:8. DOI:10.3389/fnsyn.2013.00008
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    • "Previous studies from our laboratory [67] and by others [25] have demonstrated that GABA A receptor activation in the BLA attenuates FCA. A role for glutamatergic neurotransmission in the expression of endocannabinoid-mediated FCA is also likely because on-demand synthesis and retrograde release of endocannabinoids has been demonstrated after the activation of group I metabotropic glutamate receptors [24] [44] [75] and plays a key role in the periaqueductal grey during unconditioned stress-induced analgesia [24]. We tested the hypothesis that endocannabinoid-mediated FCA is regulated by the ligand-gated chloride ion channel GABA A receptors or/and G q -protein coupled mGluR5 in the BLA, by utilising the GABA A receptor antagonist bicuculline or the mGluR5 antagonist MPEP, in combination with the CB 1 receptor antagonist AM251. "
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    ABSTRACT: The basolateral amygdala (BLA) is a key substrate facilitating the expression of fear-conditioned analgesia (FCA). However, the neurochemical mechanisms in the BLA which mediate this potent suppression of pain responding during fear remain unknown. The present study investigated the role of cannabinoid(1) (CB(1)) receptors and interactions with GABAergic (GABA(A) receptor) and glutamatergic (metabotropic glutamate receptor type 5; mGluR5) signalling in the BLA in formalin-evoked nociceptive behaviour and FCA in rats. Reexposure to a context previously paired with foot shock significantly reduced formalin-evoked nociceptive behaviour. Systemic or intra-BLA microinjection of the CB(1) receptor antagonist/inverse agonist AM251 prevented this expression of FCA, while injection of AM251 into the central nucleus of the amygdala did not. The suppression of FCA by systemic AM251 administration was partially attenuated by intra-BLA administration of either the GABA(A) receptor antagonist bicuculline or the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine, (MPEP). Bilateral microinjection of MPEP, but not bicuculline, alone into the BLA enhanced formalin-evoked nociceptive behaviour. Postmortem analyses revealed that FCA was associated with a significant increase in tissue levels of anandamide in the BLA side contralateral to intraplantar formalin injection. In addition, fear-conditioned rats exhibited a robust formalin-induced increase in levels of 2-arachidonyl glycerol and N-palmitoylethanolamide in the ipsilateral and contralateral BLA, respectively. These data suggest that CB(1) receptors in the BLA facilitate the expression of FCA, through a mechanism which is likely to involve the modulation of GABAergic and glutamatergic signalling.
    Pain 12/2012; 154(4). DOI:10.1016/j.pain.2012.12.021 · 5.84 Impact Factor
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    • "Recently, it is reported that the presynaptic GluK1 is involved in the induction of LTP in the lateral amygdala [23]. Furthermore, activation of metabotropic glutamate receptor (mGluR) subtype 5 is required for the induction of thalamicamygdala LTP [24]. "
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    ABSTRACT: The amygdala is known to be a critical brain region for emotional fear. It is believed that synaptic plasticity within the amygdala is the cellular basis of fear memory. Recent studies demonstrate that cortical areas such as the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) may also contribute to the formation of fear memory, including trace fear memory and remote fear memory. At synaptic level, fear conditioning also triggers plastic changes within the cortical areas immediately after the condition. These results raise the possibility that certain forms of synaptic plasticity may occur within the cortex while synaptic potentiation takes place within synapses in the hippocampus and amygdala. This hypothesis is supported by electrophysiological evidence obtained from freely moving animals that neurons in the hippocampus/amygdala fire synchronous activities with cortical neurons during the learning. To study fear-related synaptic plasticity in the cortex and its functional connectivity with neurons in the amygdala and hippocampus will help us understand brain mechanisms of fear and improve clinical treatment of emotional disorders in patients.
    Neural Plasticity 09/2011; 2011:813749. DOI:10.1155/2011/813749 · 3.60 Impact Factor
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