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

Kim, Joung Hun; Udo, Hiroshi; Li, Hsiu Ling; Youn, Trisha Y.; Chen, Mary; Kandel, Eric R.; Bailey, Craig H.

doi:10.1016/s0896-6273(03)00595-6

Cited by 123 publications

(139 citation statements)

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“…Mechanisms underlying the local induction of ITF include the possibility that the protein synthesis machinery and͞or the signaling pathways re- quired for ITF induction are localized to the synaptic compartment. Our results showing that induction of ITF depends on protein synthesis in the synaptic compartment support the notion of a requirement for local synaptic protein synthesis for this form of plasticity (43).…”

Section: Discussionsupporting

confidence: 85%

Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation inAplysia

Sherff

Carew²

2004

Proc. Natl. Acad. Sci. U.S.A.

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The induction of different phases of memory depends on the amount and patterning of training, raising the question of whether specific training patterns engage different cellular mechanisms and whether these mechanisms operate in series or in parallel. We examined these questions by using a cellular model of memory formation: facilitation of the tail sensory neuron-motor neuron synapses by serotonin (5-hydroxytryptamine, 5-HT) in the CNS of Aplysia. We studied facilitation in two temporal domains: intermediate-term facilitation (1.5-3 h) and long-term facilitation (LTF, >24 h). Both forms can be induced by using several different temporal and spatial patterns of 5-HT, including (i) repeated, temporally spaced pulses of 5-HT to both the sensory neuron soma and the sensory neuron-motor neuron synapse, and (ii) temporally asymmetric exposure of 5-HT to the soma and synapse under conditions in which neither exposure alone induces LTF. We first examined the protein and RNA synthesis requirements for LTF induced by these two patterns and found that asymmetric (but not repeated) 5-HT application induced LTF that required postsynaptic protein and RNA synthesis. We next focused on the patterning and protein synthesis requirements for intermediate-term facilitation. We found that intermediate-term facilitation (i) is induced locally at the synapse, (ii) requires multiple pulses of 5-HT, and (iii) requires synaptic protein synthesis. Our findings show that different temporal and spatial patterns of 5-HT induce specific temporal phases of long-lasting facilitation in parallel by engaging different cellular and molecular mechanisms. I t has long been appreciated that memories can persist in dramatically different time frames, from seconds and minutes up to a lifetime (1, 2). A major question now concerns the relationship between memories that exist in different temporal domains. One possibility, for which there is considerable empirical support (see ref. 1), is that memories are processed in series. However, there is a growing body of evidence showing that, at least under certain circumstances, memories can also be processed in parallel (3-7).Like memory, neuronal plasticity can exist in several temporal domains. This feature of plasticity has been revealed in many experimental contexts, including three model systems that have been especially useful for studying the synaptic basis for learning and memory: the mammalian hippocampus (8-11), the photoreceptor neurons in Hermissenda (12, 13), and the sensory neuron-motor neuron (SN-MN) synapses of Aplysia. In Aplysia, the tail-elicited siphon-withdrawal reflex has been useful for examining the temporal relationships between synaptic plasticity and memory. Memory for sensitization induced by repeated tail shocks can exist in at least three temporal domains: short-term memory (Ͻ25 min), intermediate-term memory (Ϸ90 min), and long-term memory (Ͼ24 h) (14-16). Because tail shock releases serotonin (5-hydroxytryptamine, 5-HT) systemically (17) On the synaptic level, ITF exists in m...

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Section: Discussionsupporting

confidence: 85%

Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation inAplysia

Sherff

Carew²

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Although intermediate-term sensitization lasts for a few hours, it is already present 25 min after training (Sutton et al 2001). Moreover, intermediate-term facilitation of sensorimotor synapses in cell culture has been previously associated with the recruitment of pre-existing, but silent, synaptic structures (Kim et al 2003). Prolonged contralateral training for LTS may, therefore, lead to an increase in the availability of immature structures, which, in turn, would require less training to formulate a sufficient number of additional synapses for the expression of intermediate-term sensitization.…”

Section: Learning and Memory 423mentioning

confidence: 99%

“…This doctrine was most clearly supported by experimental data in the 1980s, when the number and size of sensory neuron synapses were found to change after long-term sensitization in Aplysia (Bailey and Chen 1983). Although the association of structural modifications with long-term plasticity or memory has been repeatedly replicated Chen 1988a,b, 1989;Wainwright et al 2002Wainwright et al , 2004Kim et al 2003), not all training protocols that produce LTS also produce neurite outgrowth (Wainwright et al 2002). Moreover, training can also lead to axonal restructuring without apparent learning (Wainwright et al 2002(Wainwright et al , 2004.…”

mentioning

confidence: 93%

Long-term sensitization training primes Aplysia for further learning

Antzoulatos

Wainwright²,

Cleary

et al. 2006

Learn. Mem.

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Repetitive, unilateral stimulation of Aplysia induces long-term sensitization (LTS) of ipsilaterally elicited siphon-withdrawal responses. Whereas some morphological effects of training appear only on ipsilateral sensory neurons, others appear bilaterally. We tested the possibility that contralateral morphological modifications may have functional significance. Therefore, we examined whether LTS training primes subsequent sensitization. Twenty-four hours after LTS training the effects of brief shock treatment (BST) were examined. BST failed to sensitize animals that had previously received either 4-d control treatment or 4-d ipsilateral LTS training. In contrast, BST did sensitize animals that had previously received 4-d contralateral LTS training, suggesting the presence of a latent trace that primes the animal for further learning.The siphon withdrawal reflex of Aplysia is a useful model system for understanding the neurobiology of learning and memory. The reflex exhibits sensitization, a simple form of learning, in which responses elicited by weak test stimuli are augmented by training with strong, usually noxious, stimuli (Carew et al. 1971;Pinsker et al. 1973;Scholz and Byrne 1987). Short-term sensitization (lasting from seconds to minutes) relies on covalent modification of pre-existing proteins. Intermediate-term sensitization (from minutes to hours) requires translation of mRNA into protein but does not require gene transcription. Long-term sensitization (LTS) (lasting days) requires both gene transcription and translation (Sutton et al. 2001). A critical locus of learning-related plasticity is the glutamatergic synapse of sensory neurons onto target motor neurons (Antzoulatos and Byrne 2004). Several experimental observations have suggested that LTS is partly mediated by structural changes of sensory neurons, which maintain sensorimotor synapses in a facilitated state (Bailey and Chen 1983;Wainwright et al. 2002).Twenty-four hours after LTS training on the lateral body wall of intact Aplysia, the siphon withdrawal reflex is sensitized only when evoked by test stimuli on the side of the tail ipsilateral to the trained body wall. When test stimulation is delivered to the contralateral side of the tail, siphon responses are normal (i.e., non-sensitized), similar to the responses of untrained animals (Wainwright et al. 2002). The ipsilateral effect of unilateral training suggests that a critical part of memory may be stored in the ipsilateral pleural-pedal ganglia, that is, the part of the Aplysia central nervous system that mediates the afferent limb of the reflex. Consequently, sensory neurons of only the ipsilateral ganglia would be expected to change after LTS training. Indeed, the number of sensorimotor appositions and the amplitude of sensorimotor excitatory postsynaptic potentials increased only on the ipsilateral side of trained animals. Surprisingly, other structural features of sensory neurons, such as the number of varicosities and the length of neurites, did change on the contralateral side (Wai...

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“…On the one hand, under some circumstances short-and long-term plasticity can be produced independently, suggesting that they may be induced in parallel (Emptage and Carew 1993). On the other hand, in both Aplysia and hippocampus an intermediate-term stage of plasticity has been identified that usually involves protein but not RNA synthesis and structural alterations but not synaptic growth, and therefore might form a bridge between short-and long-term plasticity (Ghirardi et al 1995;Winder et al 1998;Sutton and Carew 2000;Sutton et al 2001;Kim et al 2003;Li et al 2005Li et al , 2009Villareal et al 2007). That idea in turn suggests that aspects of the different stages of plasticity may be induced in series, similar to the states in artificial "cascade" models of memory storage (Fusi et al 2005).…”

mentioning

confidence: 99%

Whereas short-term facilitation is presynaptic, intermediate-term facilitation involves both presynaptic and postsynaptic protein kinases and protein synthesis

Jin¹,

Kandel²,

Hawkins³

2011

Learn. Mem.

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Whereas short-term plasticity involves covalent modifications that are generally restricted to either presynaptic or postsynaptic structures, long-term plasticity involves the growth of new synapses, which by its nature involves both pre-and postsynaptic alterations. In addition, an intermediate-term stage of plasticity has been identified that might form a bridge between short-and long-term plasticity. Consistent with that idea, although short-term term behavioral sensitization in Aplysia involves presynaptic mechanisms, intermediate-term sensitization involves both pre-and postsynaptic mechanisms. However, it has not been known whether that is also true of facilitation in vitro, where a more detailed analysis of the mechanisms involved in the different stages and their interrelations is feasible. To address those questions, we have examined preand postsynaptic mechanisms of short-and intermediate-term facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture. Whereas short-term facilitation by 1-min 5-HT involves presynaptic PKA and CamKII, intermediate-term facilitation by 10-min 5-HT involves presynaptic PKC and postsynaptic Ca 2+ and CamKII, as well as both pre-and postsynaptic protein synthesis. These results support the idea that the intermediate-term stage is the first to involve both pre-and postsynaptic molecular mechanisms, which could in turn serve as some of the initial steps in a cascade leading to synaptic growth during long-term plasticity.

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

Cited by 123 publications

References 50 publications

Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation inAplysia

Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation inAplysia

Long-term sensitization training primes Aplysia for further learning

Whereas short-term facilitation is presynaptic, intermediate-term facilitation involves both presynaptic and postsynaptic protein kinases and protein synthesis

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