Long-Term Sensitization in Aplysia : Biophysical Correlates in Tail Sensory Neurons

Neural correlates of long-term sensitization of defensive withdrawal reflexes in Aplysia occur in sensory neurons in the pleural ganglia and can be mimicked by exposure of these neurons to serotonin (5-HT). Studies using inhibitors indicate that transcription is necessary for production of long-term facilitation by 5-HT. Several mRNAs that change in response to 5-HT have been identified, but the molecular events responsible for long-term facilitation have not yet been fully described. To detect additional changes in mRNAs, we investigated the effects of 5-HT (1.5 hr) on levels of mRNA in pleural-pedal ganglia using in vitro translation. Four mRNAs were affected by 5-HT, three of which were identified as calmodulin (CaM), phosphoglycerate kinase (PGK), and a novel gene product (protein 3). Using RNase protection assays, we found that 5-HT increased all three mRNAs in the pleural sensory neurons. CaM and protein 3 mRNAs were also increased in the sensory neurons 4Corresponding author.by sensitization training. Furthermore, stimulation of peripheral nerves of pleural-pedal ganglia, an in vitro analog of sensitization training, increased the incorporation of labeled amino acids into CaM, PGK, and protein 3. These results indicate that increases in CaM, PGK, and protein 3 are part of the early response of sensory neurons to stimuli that produce long-term facilitation, and that CaM and protein 3 could have a role in the generation of long-term sensitization.

Section: -Ht Treatment Of Ganglia and Behavioral Sensitizationmentioning

confidence: 99%

Section: Behavioral Training Increased Cam and Protein 3 In Pleural Smentioning

confidence: 99%

Identification of specific mRNAs affected by treatments producing long-term facilitation in Aplysia.

Zwartjes

West

Hattar³

et al. 1998

“…Whereas a single tail shock induces short-term memory (STM) for sensitization lasting minutes, repeated spaced shocks produce LTM for sensitization lasting days to weeks (Frost et al 1985;Scholz and Byrne 1987;Castellucci et al 1989;Goldsmith and Byrne 1993;Cleary et al 1998;Levenson et al 2000;Sutton et al 2001a;see also, Carew et al 1971;Pinsker et al 1973). Recently, we distinguished a third phase of memory for sensitization, intermediate-term memory (ITM), that is induced by repeated spaced shocks and lasts 1-3 h after training (Sutton et al 2001a).…”

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confidence: 95%

Interaction between Amount and Pattern of Training in the Induction of Intermediate- and Long-Term Memory for Sensitization in Aplysia

Sutton¹,

Ide²,

Masters³

et al. 2002

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118

In Aplysia, three distinct phases of memory for sensitization can be dissociated based on their temporal and molecular features. A single training trial induces short-term memory (STM, lasting <30 min), whereas five trials delivered at 15-min intervals induces both intermediate-term memory (ITM, lasting >90 min) and long-term memory (LTM, lasting >24 h). Here, we explore the interaction of amount and pattern of training in establishing ITM and LTM by examining memory for sensitization after different numbers of trials (each trial = one tail shock) and different patterns of training (massed vs. spaced). Under spaced training patterns, two trials produced STM exclusively, whereas four or five trials each produced both ITM and LTM. Three spaced trials failed to induce LTM but did produce an early decaying form of ITM (E-ITM) that was significantly shorter and weaker in magnitude than the late-decaying ITM (L-ITM) observed after four to five trials. In addition, E-ITM was induced after three trials with both massed and spaced patterns of training. However, L-ITM and LTM after four to five trials require spaced training: Four or five massed trials failed to induce LTM and produced only E-ITM. Collectively, our results indicate that in addition to three identified phases of memory for sensitization-STM, ITM, and LTM-a unique temporal profile of memory, E-ITM, is revealed by varying either the amount or pattern of training.

“…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.…”

mentioning

confidence: 99%

Long-term sensitization training primes Aplysia for further learning

Antzoulatos

Wainwright²,

Cleary

et al. 2006

Self Cite

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...