Long-term heterosynaptic inhibition in Aplysia

Montarolo, P. G.; Kandel, Eric R.; Schacher, Samuel

doi:10.1038/333171a0

Cited by 113 publications

(93 citation statements)

References 19 publications

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“…Thus, this form of decremental plasticity at any interneuronal site is a reasonable candidate to contribute to habituation. Inhibition is also well described in reflex circuits in Aplysia, and many authors have speculated that this process may play a role in habituation of both siphon-and tail-elicited responses (Montarolo et al, 1988;Schacher and Montarolo, 1991;Wright et al, 1991;Buonomano et al, 1992;Fischer and Carew, 1993). Thus, the buildup of inhibition (possibly driven in part by the facilitation of the sensory neuron output during habituation that we observe) at interneuronal sites is certainly a reasonable candidate mechanism for habituation in Aplysia.…”

Section: Additional Sites and Mechanisms Of Habituationmentioning

confidence: 80%

Heterosynaptic Facilitation of Tail Sensory Neuron Synaptic Transmission during Habituation in Tail-Induced Tail and Siphon Withdrawal Reflexes ofAplysia

Stopfer¹,

Carew

1996

J. Neurosci.

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In cellular studies of habituation, such as in the gill and siphon withdrawal reflex to tactile stimulation of the siphon of Aplysia, a mechanism that has emerged as an explanation for response decrement during habituation is homosynaptic depression at sensory neurons mediating the behavioral response. We have examined the contribution of homosynaptic depression to habituation in sensory neurons that contribute to two reflex behaviors in Aplysia, tail withdrawal and siphon withdrawal, both elicited by threshold-level tail stimulation. In a companion paper (this issue), we reported that repeated tail stimulation, identical to that producing habituation in siphon withdrawal in freely moving animals, also produces habituation in reduced preparations. In this paper, we extend these behavioral findings by showing that in reduced preparations, identical tail stimulation also produces habituation of the tail withdrawal reflex. In addition, our cellular experiments show that (1) identified sensory and motor neurons in both reflex systems respond to identical repeated tail stimulation; in sensory neurons it produces a progressive decrease in spike number and increase in spike latency, and in motor neurons it produces progressive decrement in complex EPSPs and spike output. (2) Homosynaptic depression of the tail sensory neuron to tail motor neuron synapse does occur when the sensory neurons are activated repetitively by intracellular current. (3) Homosynaptic depression at this synapse does not occur when the sensory neurons are activated repetitively by threshold-level tail stimuli that elicit the behavioral reflex and cause habituation; rather, the sensory neurons exhibit significant heterosynaptic facilitation. Thus, in these reflexes, habituation is not accompanied by homosynaptic depression at the sensory neurons, suggesting that the plasticity underlying habituation occurs primarily at interneuronal sites.

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Section: Additional Sites and Mechanisms Of Habituationmentioning

confidence: 80%

Heterosynaptic Facilitation of Tail Sensory Neuron Synaptic Transmission during Habituation in Tail-Induced Tail and Siphon Withdrawal Reflexes ofAplysia

Stopfer¹,

Carew

1996

J. Neurosci.

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“…We focused on CREB2 because of its critical role in setting the threshold for long-term synaptic plasticity and memory in both Aplysia and mice (12)(13)(14)(15)(16). Thus, in Aplysia, CREB2 activity is specifically required for LTD of sensory-motor synapses induced by the neuropeptide FMRFamide (17)(18)(19). In rodent hippocampus, the translationally regulated expression of CREB2/ATF4 bidirectionally controls long-term plasticity and memory (16).…”

mentioning

confidence: 99%

Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons

Lai¹,

Zhao²,

Ch’ng³

et al. 2008

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

104

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Signals received at distal synapses of neurons must be conveyed to the nucleus to initiate the changes in transcription that underlie long-lasting synaptic plasticity. The presence of importin nuclear transporters and of select transcription factors at synapses raises the possibility that importins directly transport transcription factors from synapse to nucleus to modulate gene expression. Here, we show that cyclic AMP response element binding protein 2 (CREB2)/activating transcription factor 4 (ATF4), a transcriptional repressor that modulates long-term synaptic plasticity and memory, localizes to distal dendrites of rodent hippocampal neurons and neurites of Aplysia sensory neurons (SNs) and binds to specific importin ␣ isoforms. Binding of CREB2 to importin ␣ is required for its transport from distal dendrites to the soma and for its translocation into the nucleus. CREB2 accumulates in the nucleus during long-term depression (LTD) but not long-term potentiation of rodent hippocampal synapses, and during LTD but not long-term facilitation (LTF) of Aplysia sensory-motor synapses. Time-lapse microscopy of CREB2 tagged with a photoconvertible fluorescent protein further reveals retrograde transport of CREB2 from distal neurites to the nucleus of Aplysia SN during phenylalaninemethionine-arginine-phenylalanine-amide (FMRFamide)-induced LTD. Together, our findings indicate that CREB2 is a novel cargo of importin ␣ that translocates from distal synaptic sites to the nucleus after stimuli that induce LTD of neuronal synapses.Aplysia ͉ hippocampus ͉ transcription ͉ long-term depression ͉ dendra S ynaptic plasticity is critical to cognition and memory formation. Long-lasting forms of synaptic plasticity require both transcription and translation (1-3), and specific patterns and strengths of synaptic stimulation trigger changes in neuronal gene expression (4). However, relatively little is known about how signals are transported from synapse to nucleus to regulate transcription. Many types of synaptic stimulation induce depolarization and electrochemical signaling to rapidly alter transcription in the nucleus (5). A slower, more persistent mechanism of signaling to the nucleus involves the transport of soluble molecules from stimulated synapses to the nucleus (6, 7). Recent studies have indicated that this type of transport may involve the active nuclear import pathway (8-10).In the classical nuclear import pathway, proteins bearing nuclear localization signals (NLSs) bind an adaptor protein of the importin ␣ family, which in turn binds the importin ␤1 nuclear transporter. Importin ␤1 mediates facilitated translocation of this heterotrimeric complex across the nuclear pore. In neurons, importins may also function to carry signals from distal neuronal processes to the soma and into the nucleus (8-11). This finding raises a critical question: what are the synaptically localized cargoes of importins that translocate to the nucleus to alter transcription during synaptic plasticity?One attractive class of potential importin...

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“…Cultured sensory-motor neuron synapses have been found to retain nearly every nonassociative form of plasticity they exhibit in vivo, including short-term homosynaptic depression and potentiation, and both short-and long-term heterosynaptic facilitation and inhibition (Montarolo et al, 1986(Montarolo et al, , 1988Rayport and Schacher, 1986;Schacher et al, 1990;Eliot et al, 1990). Can associative forms of plasticity also be reproduced in culture?…”

mentioning

confidence: 99%

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

et al. 1994

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Synapses made by Aplysia sensory neurons onto motor- and interneuron followers in the intact nervous system exhibit an associative form of synaptic facilitation that is thought to contribute to classical conditioning of the animal's gill and siphon withdrawal reflex (Hawkins et al., 1983; Walters and Byrne, 1983). Here we demonstrate that a similar associative facilitation can be induced between individual sensory and motor neurons isolated in culture. Pairing tetanic stimulation with either of two facilitatory transmitters, 5-HT or small cardioactive peptide, considerably prolongs facilitation compared to either tetanus or transmitter alone. When corrected for the depression that occurs simply in response to low-frequency testing, the facilitation produced by one pairing trial does not decay for more than 20 min after training. This facilitation requires the temporal pairing (0.5 sec forward interstimulus interval) of the two stimuli, tetanus and 5-HT. Delivering the same two stimuli in an unpaired fashion (1 min forward interval) fails to produce the long-lasting effect. Measurements of spontaneous transmitter release during either paired or unpaired training reveal no changes in unitary mEPSP or mEPSC (“mini”) amplitude, indicating that the facilitation involves a presynaptic mechanism. While both forms of training dramatically increase the initial frequency of spontaneous release, mini frequency does not remain elevated as long as the evoked EPSP following paired training, nor does paired training specifically enhance spontaneous release frequency. Pairing-specific facilitation was not blocked by the protein kinase C inhibitor H7. In contrast, the same training procedure produced pairing-specific increases of sensory neuron excitability and action potential width, suggesting that cAMP-mediated processes are involved in the paired effect. Although Ca2+ influx is necessary for the associative effect (Abrams, 1985), we find that the facilitation does not require influx through L-type voltage-gated Ca2+ channels, since the effect was not blocked by the dihydropyridine antagonist nitrendipine. Together, these findings indicate that the mechanism underlying associative, activity-dependent facilitation is intrinsic to the sensory neuron synapse, that it is presynaptically mediated by processes unique to evoked synaptic transmission, and that it appears to involve a pairing-specific broadening of the presynaptic action potential, allowing enhanced Ca2+ influx through the dihydropyridine- insensitive channels responsible for release.

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Long-term heterosynaptic inhibition in Aplysia

Cited by 113 publications

References 19 publications

Heterosynaptic Facilitation of Tail Sensory Neuron Synaptic Transmission during Habituation in Tail-Induced Tail and Siphon Withdrawal Reflexes ofAplysia

Heterosynaptic Facilitation of Tail Sensory Neuron Synaptic Transmission during Habituation in Tail-Induced Tail and Siphon Withdrawal Reflexes ofAplysia

Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

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