Article

Presynaptic Activation of Silent Synapses and Growth of New Synapses Contribute to Intermediate and Long-Term Facilitation in Aplysia

Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
Neuron (Impact Factor: 15.98). 10/2003; 40(1):151-65. DOI: 10.1016/S0896-6273(03)00595-6
Source: PubMed

ABSTRACT The time course and functional significance of the structural changes associated with long-term facilitation of Aplysia sensory to motor neuron synaptic connections in culture were examined by time-lapse confocal imaging of individual sensory neuron varicosities labeled with three different fluorescent markers: the whole-cell marker Alexa-594 and two presynaptic marker proteins-synaptophysin-eGFP to monitor changes in synaptic vesicle distribution and synapto-PHluorin to monitor active transmitter release sites. Repeated pulses of serotonin induce two temporally, morphologically, and molecularly distinct presynaptic changes: (1) a rapid activation of silent presynaptic terminals by filling of preexisting empty varicosities with synaptic vesicles, which parallels intermediate-term facilitation, is completed within 3-6 hr and requires translation but not transcription and (2) a slower generation of new functional varicosities which occurs between 12-18 hr and requires transcription and translation. Enrichment of empty varicosities with synaptophysin accounts for 32% of the newly activated synapses at 24 hr, whereas newly formed varicosities account for 68%.

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    • "This schema places all presynaptic terminals at equal distance from the cell body, hence implying equal probabilities for the distribution of subcellular organelles, proteins and mRNA (Kim et al., 2003; Bailey and Kandel, 2008). Whereas significant differences in the properties of the individual terminal boutons are considered in relation to long-term plasticity of the neurons, the underlying mechanisms are not discussed (Kim et al., 2003). Intuitively if all terminal boutons are equally distributed from the cell body, no innate presynaptic differences in their subcellular structure and physiology would be expected. "
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    ABSTRACT: Much of what we know about the mechanisms underlying Homosynaptic Depression (HSD) and heterosynaptic facilitation is based on intracellular recordings of integrated postsynaptic potentials (PSPs). This methodological approach views the presynaptic apparatus as a single compartment rather than taking a more realistic representation reflecting the fact that it is made up of tens to hundreds of individual and independent Presynaptic Release Boutons (PRBs). Using cultured Aplysia sensorimotor synapses, we reexamined HSD and its dishabituation by imaging the release properties of individual PRBs. We find that the PRB population is heterogeneous and can be clustered into three groups: ~25% of the PRBs consistently release neurotransmitter throughout the entire habituation paradigm (35 stimuli, 0.05 Hz) and have a relatively high quantal content, 36% of the PRBs display intermittent failures only after the tenth stimulation, and 39% are low quantal-content PRBs that exhibit intermittent release failures from the onset of the habituation paradigm. 5HT-induced synaptic dishabituation by a single 5HT application was generated by the enhanced recovery of the quantal content of the habituated PRBs and did not involve the recruitment of new release boutons. The characterization of the PRB population as heterogeneous in terms of its temporal pattern of release-probability and quantal content provides new insights into the mechanisms underlying HSD and its dishabituation.
    Frontiers in Cellular Neuroscience 09/2013; 7:165. DOI:10.3389/fncel.2013.00165 · 4.18 Impact Factor
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    • "In our model, this increase in probability and speed of neurotransmitter release may reflect a positive modulation of release machinery induced by epileptiform activity, perhaps through transient protein modification such as phosphorylation or increased Ca2+ concentration in the presynaptic terminals [72]. Alternatively, we cannot exclude the rapid activation of other active zones that were previously silent [73]. An enhancement in amplitude of evoked postsynaptic currents and a shortening of their rise times have also been described in basolateral amygdala neurons of rats which undergo to epileptic discharges induced by electrical kindling [74]. "
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    PLoS ONE 02/2013; 8(2):e56968. DOI:10.1371/journal.pone.0056968 · 3.23 Impact Factor
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    • "suggested that there is rapid activation of silent synapses and slower generation of new synapses in Aplysia sensory-motor cocultures during synaptic potentiation (Kim et al., 2003). The formation of new release sites has also been observed in cultured hippocampal neurons by examining the distribution of presynaptic vesicle proteins tagged either with green fluorescent protein (GFP) for live imaging or immunostained for static imaging (Antonova et al., 2001, 2009; Ninan et al., 2006). "
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