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: 9.67). 10/2010; 107(44):19073-8. DOI: 10.1073/pnas.1009803107
Source: PubMed


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.

10 Reads
  • Source
    • "To date, most forms of LTP reported in the ACC are postsynaptically induced. Our recent study reported that a new pairing protocol can induce LTP in the ACC that is purely presynaptically induced [24,25]. This presynaptic form of LTP (called pre-LTP) is completely independent of activation of postsynaptic NMDA receptors, and does not require calcium-dependent signalling pathways at postsynaptic sites. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery 'teach' humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, 'erasing' or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.
    Philosophical Transactions of The Royal Society B Biological Sciences 01/2014; 369(1633):20130146. DOI:10.1098/rstb.2013.0146 · 7.06 Impact Factor
  • Source
    • "These findings are primarily based on the effects of manipulating AEA signaling; however, no studies to date have examined site-specific effects of MGL inhibition. As anxiety is typically associated with reduced activity in the PFC and enhanced activity in the amygdala, it is not surprising that electrophysiological evidence has demonstrated that eCB signaling in the PFC can enhance neuronal activity through a suppression of γ-aminobutyric acid (GABA) release [48,49], while suppressing glutamate release and excitability within the amygdala [50-53]. Accordingly, the current data would suggest that eCB signaling increases prefrontal cortical activity and suppresses amygdalar activation to dampen the expression of anxiety-like behaviors in rodents. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Accumulating evidence over the past decade has highlighted an important role of the endocannabinoid (eCB) system in the regulation of stress and emotional behavior across divergent species, from rodents to humans. The general findings from this work indicate that the eCB system plays an important role in gating and buffering the stress response, dampening anxiety and regulating mood. Work in rodents has allowed researchers to determine the neural mechanisms mediating this relationship while work in human populations has demonstrated the possible importance of this system in stress-related psychiatric diseases, such as post-traumatic stress disorder, generalized anxiety and major depression. These stress-protective effects of eCB signaling appear to be primarily mediated by their actions within corticolimbic structures, particularly the amygdala and the prefrontal cortex. The aim of this review is to provide an up-to-date discussion of the current level of knowledge in this field, as well as address the current gaps in knowledge and specific areas of research that require attention.
    Biology of Mood and Anxiety Disorders 10/2013; 3(1):19. DOI:10.1186/2045-5380-3-19
  • Source
    • ") 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) "
    [Show abstract] [Hide abstract]
    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
Show more


10 Reads
Available from