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Ken Lukowiak - One of the best experts on this subject based on the ideXlab platform.
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Intermediate and long-term Memory are different at the neuronal level in Lymnaea stagnalis (L.)
Neurobiology of Learning and Memory, 2011Co-Authors: Marvin H. Braun, Ken LukowiakAbstract:Abstract Both Intermediate-Term Memory (ITM) and long-term Memory (LTM) require novel protein synthesis; however, LTM also requires gene transcription. This suggests that the behavioural output of the two processes may be produced differently at the neuronal level. The fresh-water snail, Lymnaea stagnalis , can be operantly conditioned to decrease its rate of aerial respiration and, depending on the training procedure, the Memory can last 3 h (ITM) or >24 h (LTM). RPeD1, one of the 3 interneurons that form the respiratory central pattern generator (CPG) that drives aerial respiration, is necessary for Memory formation. By comparing RPeD1’s electrophysiological properties in naive, ‘ITM-trained’, ‘LTM-trained’ and yoked control snails we discovered that while the behavioural phenotype of Memory at 3 and 24 h is identical, the situation at the neuronal level is different. When examined 3 h after either the ‘ITM’ or ‘LTM’ training procedure RPeD1 activity is significantly depressed. That is, the firing rate, input resistance, excitability and the number of action potential bursts are all significantly decreased. In snails receiving the ITM-training, these changes return to normal 24 h post-training. However, in snails receiving the ‘LTM-training’, measured RPeD1 properties (firing rate, excitability, membrane resistance, and the number of action potential bursts fired) are significantly different at 24 h than they were at 3 h. Additionally, 24 h following LTM training RPeD1 appears to be functionally “uncoupled” from its control of the pneumostome as the link between RPeD1 excitation and pneumostome opening is weakened. These data suggest that the behavioural changes occurring during LTM are due to more widespread neuronal reorganization than similar behavioural changes occurring during ITM. Thus ITM and LTM are not just distinct in a chronological and transcriptional manner but are also distinct at the level of neuronal properties.
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Differences in LTM-forming capability between geographically different strains of Alberta Lymnaea stagnalis are maintained whether they are trained in the lab or in the wild.
Journal of Experimental Biology, 2009Co-Authors: Mike Orr, Ken Lukowiak, Karla Hittel, J. HanAbstract:We found strain differences in the ability of wild Alberta Lymnaea stagnalis to form long-term Memory (LTM) following operant conditioning when L. stagnalis were collected from the wild and trained in the laboratory. Lymnaea stagnalis obtained from the Belly River watershed had an enhanced ability to form LTM compared with those from an isolated pond (referred to as Jackson snails). We therefore asked whether the differences in cognitive ability were an epiphenomenon as a result of training in the laboratory. To answer this question we trained each specific strain (Belly and Jackson) in both the laboratory and the field (i.e. in their home pond and in the pond where the other strain resided - referred to as the visitor pond). We found that within each strain there was no difference in the LTM phenotype whether they were trained in the lab or in either their home or visitor pond. That is, the strain differences in the ability to form LTM were still present. Interestingly, we found no strain differences in the ability to learn or the ability to form Intermediate-Term Memory (ITM).
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Electrophysiological and Behavioral Evidence Demonstrating That Predator Detection Alters Adaptive Behaviors in the Snail Lymnaea
Journal of Neuroscience, 2008Co-Authors: Michael V. Orr, Ken LukowiakAbstract:Stress has been shown to both impair and enhance learning, long-term Memory (LTM) formation, and/or its recall. The pond snail, Lymnaea stagnalis , both detects and responds to the scent of a crayfish predator with multiple stress-related behavioral responses. Using both behavioral and electrophysiological evidence, this investigation is a first attempt to characterize how an environmentally relevant stressor (scent of a predator) enhances LTM formation in Lymnaea . Using a training procedure that, in “standard” pond water (PW), results in an Intermediate-Term Memory that persists for only 3 h, we found that training snails in “crayfish effluent” (CE) induces a Memory that persists for 48 h (i.e., its now an LTM). In addition, if we use a training procedure that in PW produces an LTM that persists for 1 d, we find that snails trained in CE have an LTM that persists for at least 8 d. Furthermore, we describe how a single neuron (RPeD1), which has been shown to be a necessary site for LTM formation, reflects the behavioral changes in its firing properties that persist for the duration of the LTM. Finally, Lymnaea exhibit context-specific Memory, that is, when a Memory is formed in a specific context (food odorant), it is only recalled in that context. Here, we found that snails trained in CE demonstrate context generalization, that is, Memory is recalled in multiple contexts. All data are consistent with the hypothesis that learning in a stressful, yet biologically relevant, environment enhances LTM and prolongs its retention.
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Intermediate and long-term memories of associative learning are differentially affected by transcription versus translation blockers in Lymnaea.
Journal of Experimental Biology, 2003Co-Authors: Susan Sangha, Andi Scheibenstock, Chloe Mccomb, Ken LukowiakAbstract:Aerial respiratory behaviour in the pond snail, Lymnaea stagnalis, can be operantly conditioned. This associative learning then undergoes consolidation into a long-lasting Memory which, depending on the training procedure used, causes Intermediate-Term Memory (ITM; lasting 3 h) or long-term Memory (LTM; lasting >6 h) to be formed. We determined the differential susceptibility of these two forms of Memory to translation and transcription blockers. The injection of a translation blocker, Anisomycin, 2.5 h before training prevents the establishment of both ITM and LTM. On the other hand, injection of the transcription blocker Actinomycin D, 2.5 h before training, did not prevent the establishment of ITM, but did, however, prevent LTM formation. Thus in Lymnaea , following associative learning, both ITM and LTM are dependent on new protein synthesis. ITM appears to be dependent on protein synthesis from preexisting transcription factors, whilst LTM is dependent on protein synthesis from new transcription messages.
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Operant conditioning in Lymnaea: evidence for intermediate- and long-term Memory.
Learning & Memory, 2000Co-Authors: Ken Lukowiak, Darin Krygier, Nimet Adatia, Naweed I. SyedAbstract:Aerial respiration of the pond snail, Lymnaea stagnalis, can be operantly conditioned; however, the parameters necessary to produce long-term (LTM) or intermediate term Memory (ITM) have not previously been investigated. We conducted training using procedures that varied in the duration of the training session, the number of training sessions per day or the amount of time between subsequent training sessions (SI). We found that by varying the duration and frequency of the training session learning could be differentially produced. Furthermore, the ability to form LTM was dependent not only on the duration of the training session was also the interval between training sessions, the SI. Thus it was possible to produce ITM, which persists for up to 3 hr, and not form LTM, which persists at least 18 hr. Learning, ITM, and LTM can be differentially produced by altering the SI, the duration of the training session, or the number of training sessions per day. These findings may allow us to begin to elucidate the underlying neural mechanisms of learning, ITM, and LTM.
Arturo Romano - One of the best experts on this subject based on the ideXlab platform.
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Two critical periods for cAMP-dependent protein kinase activity during long-term Memory consolidation in the crab Chasmagnathus.
Neurobiology of Learning and Memory, 2002Co-Authors: Fernando Locatelli, Héctor Maldonado, Arturo RomanoAbstract:Abstract Activation of the cAMP pathway was found to be implicated in the Memory process. In the context-signal learning paradigm of the crab Chasmagnathus , the protein kinase (PKA) activator Sp-5,6-DCl-cBIMPS facilitated long-term Memory (LTM) induced by spaced training while the PKA inhibitor 8-chloroadenosine-3′, 5′-monophosphorothioate, Rp-isomer (Rp-8-Cl-cAMPS) produced amnesia. In the present report the effect of the PKA inhibitor on long-term retention was assessed when administered (systemic injection of 2 μg/animal) at various times after training. According to previous results obtained with a lower dose, retention is impaired when the drug is administered immediately pretraining. An effect on acquisition was ruled out considering that the drug did not affect the performance during training. On the contrary, no effect of the PKA inhibitor was found with an immediately posttraining injection and amnesia was observed only when training was shortened from 15 to 12 trials (training duration from 45 to 36 min). At 2 and 12 h posttraining Rp-8-Cl-cAMPS injection failed to impair retention, but amnesia was found when the drug was injected at 4 and 8 h after training. In order to assess a possible effect of the drug in retrieval, the PKA inhibitor was administered 15 min before testing, and no amnestic effect was observed. These results suggest that two phases of PKA activity are required during consolidation of LTM, one during training and the other between 4 and 8 h after training. The link between these two periods of PKA activation and the two phases of the transcription factor NF-κB activation previously found in this model, as well as the similar time course found in rodents, is discussed. An amnestic effect of the drug was not found when administered immediately before a massed training protocol that yielded an Intermediate-Term Memory, suggesting that in this type of Memory PKA activation is not required.
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Participation of Rel/NF-κB transcription factors in long-term Memory in the crab Chasmagnathus
Brain Research, 2000Co-Authors: Ramiro Freudenthal, Arturo RomanoAbstract:Abstract The induction of gene expression has been correlated with long-lasting neuronal plasticity and long-term Memory (LTM) formation. The fast activation of constitutive transcription factors by signaling mechanisms is thought to be the link between synaptic events and gene expression. However, only one constitutive transcription factor, CREB, has been shown to play a key role in several Memory paradigms, both in vertebrates and invertebrates. Here, we report evidences for Rel/NFκ-B constitutive transcription factors participation in Memory. Using the LTM paradigm in the crab Chasmagnathus, an enhancement of NFκ-B DNA-binding activity was found after spaced training, which induces LTM, but not after massed training which yields an Intermediate-Term Memory (ITM). Such finding is correlated with the requirement of protein synthesis for LTM consolidation but not for ITM. Furthermore, NFκ-B activation was observed after 15 or 30 training trials, which are sufficient to induce LTM, but not after 5 or 10 trials, a number of trials insufficient to induce LTM. The kinetics of activation was studied and two waves of DNA-binding activity were found, similar to the time course described in other systems. NFκ-B activation after training was also found in synaptosomal extracts. The latter result supports the hypothesis of a novel synapse-to-nucleus signaling system, in which the transcription factor is locally activated by synaptic events and then transported to the nucleus.
Ayako Tonoki - One of the best experts on this subject based on the ideXlab platform.
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Age-Related Changes in Insulin-like Signaling Lead to Intermediate-Term Memory Impairment in Drosophila
Cell Reports, 2017Co-Authors: Kento Tanabe, Motoyuki Itoh, Ayako TonokiAbstract:Insulin and insulin-growth-factor-like signaling (IIS) plays important roles in the regulation of development, growth, metabolic homeostasis, and aging, as well as in brain functions such as learning and Memory. The temporal-spatial role of IIS in learning and Memory and its effect on age-dependent Memory impairment remain unclear. Here, we report that Intermediate-Term Memory (ITM), but not short-term Memory (STM), in Drosophila aversive olfactory Memory requires transient IIS during adulthood. The expression of Drosophila insulin-like peptide 3 (Dilp3) in insulin-producing cells and insulin receptor function in the fat body are essential for ITM. Although the expression of dilp3 decreases with aging, which is unique among dilp genes, the transient expression of dilp3 in aged flies enhances ITM. These findings indicate that ITM is systemically regulated by communication between insulin-producing cells and fat body and that age-dependent changes in IIS contribute to age-related Memory impairment.
Thomas J. Carew - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of calcineurin facilitates the induction of Memory for sensitization in Aplysia: Requirement of mitogen-activated protein kinase
Proceedings of the National Academy of Sciences, 2003Co-Authors: Shiv K. Sharma, Michael A. Sutton, Martha W. Bagnall, Thomas J. CarewAbstract:The induction of both synaptic plasticity and Memory is thought to depend on the balance between opposing molecular regulatory factors, such as protein kinases and phosphatases. Here we show that inhibition of protein phosphatase 2B (calcineurin, CaN) facilitates the induction of Intermediate-Term Memory (ITM) and long-term Memory (LTM) for tail shock-induced sensitization in Aplysia without any effect on short-term Memory. To identify the molecular cascade underlying the improvement of Memory by inhibition of CaN, we examined the role of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase (MAPK). Molecular experiments revealed that one pulse of serotonin, which by itself does not activate MAPK, leads to significant MAPK activation in the sensory neurons of the pleural ganglia when CaN is inhibited. Extending these observations, behavioral experiments showed that the facilitated induction of ITM and LTM produced by CaN inhibition depends on MAPK activity. These results demonstrate: (i) that CaN acts as an inhibitory constraint in the formation of long-lasting phases of Memory, and (ii) that facilitated induction of ITM and LTM by CaN inhibition requires MAPK activity.
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interaction between amount and pattern of training in the induction of intermediate and long term Memory for sensitization in aplysia
Learning & Memory, 2002Co-Authors: Michael A. Sutton, Sarah E. Masters, Thomas J. CarewAbstract:The search for the cellular and molecular basis of Memory has been significantly enhanced by the elucidation of general principles of Memory formation across diverse species. For example, Memory retention is highly sensitive not only to the total amount of training but also to the pattern of trials used during training. In particular, in a variety of tasks across species ranging from invertebrates to humans, training trials distributed over time (spaced training) typically lead to superior retention compared with training in which trials are presented with little or no rest interval (massed training) (Ebbinghaus 1885; Carew et al. 1972; Salafia et al. 1973; Lefebvre and Sabourin 1977; Fanselow and Tighe 1988; Tully et al. 1994; Hermitte et al. 1999; Muzzio et al. 1999; Menzel et al. 2001). Perhaps the most interesting feature of the superiority of spaced over massed training is that it is not a general effect for all temporal domains of Memory but rather appears to become more pronounced with longer-lasting memories (e.g., Carew et al. 1972; Tully et al. 1994; Menzel 2001). Thus, an understanding of the behavioral, cellular, and molecular factors contributing to the massed versus spaced effect could yield considerable insight into the overall organization of multiple phases of Memory. Despite the widespread conservation of the massed versus spaced effect in behavioral studies of Memory, some of the key cellular and molecular features that contribute to this feature of Memory formation are only now beginning to be understood. For example, induction of a transcriptional activator isoform of cAMP response element binding protein (CREB) in Drosophila enhances long-term Memory (LTM) for olfactory conditioning after massed patterns of training, which normally do not induce LTM; conversely, induction of a dominant-negative transcriptional repressor CREB isoform impairs LTM after spaced training (Yin et al. 1994, 1995). These findings led to the hypothesis that massed versus spaced training effects may depend on differential decay kinetics of transcriptionally activating versus transcriptionally repressing isoforms of CREB, allowing for the presumably slower decaying CREB activator to build up across spaced (but not massed) training trials (Yin et al. 1995; see also, Smolen et al. 1998). In addition to the possible role of transcription factors such as CREB, other evidence has indicated that differential activation of signaling molecules upstream from CREB may also contribute to the massed versus spaced effect. For example, Wu et al. (2001) have shown that four spaced depolarizations (3 min each) of cultured hippocampal neurons lead to a persistent phosphorylation (and, presumably, activation) of MAP kinase, whereas continuous (massed) depolarization for 12 min does not. Thus, the temporal dynamics of MAP kinase activation in the hippocampus seem to be highly dependent on the pattern of stimulation. In addition, using an analog of classical conditioning in Hermissenda, Muzzio et al. (1999) provide evidence that the accumulation of intracellular calcium and preferential activation of protein phosphatases by massed relative to spaced training may also contribute to massed versus spaced effects, indicating that massed training may, in some cases, generate processes that compete with Memory formation. These studies highlight the number of potential molecular substrates that may contribute to superior Memory retention after spaced relative to massed training. Moreover, they indicate that the relative superiority of spaced training may reflect an increased ability of spaced training to engage constructive Memory processes or an increased propensity of massed training to engage processes that interfere with normal Memory formation. One model system that is well suited for studying the effects of patterning on Memory formation is the marine mollusk Aplysia. Aplysia has proven particularly valuable for the cellular and molecular analysis of behavioral sensitization, an elementary form of nonassociative learning in which behavioral responses to a weak stimulus increase in magnitude and duration after the presentation of a noxious stimulus. In Aplysia, sensitization is most often assessed by the degree to which defensive reflexes, such as tail-elicited siphon withdrawal (T-SW), become enhanced after noxious stimuli such as tail shock. Considerable evidence indicates that facilitation of sensory neuron to motor neuron (SN-MN) synapses by serotonin (5HT), a neuromodulator released in the CNS after tail shock (Marinesco and Carew, 2002; see also Levenson et al. 1999), is an important cellular mechanism contributing to behavioral sensitization. 5HT can induce three temporally and mechanistically distinct phases of SN-MN synaptic facilitation. A single 5HT pulse induces short-term facilitation (STF) lasting 24 h. Each of these phases also has unique macromolecular synthesis requirements for their induction: STF requires neither protein nor RNA synthesis, ITF requires protein but not RNA synthesis, and LTF requires both (Montarolo et al. 1986; Mercer et al. 1991; Emptage and Carew, 1993; Ghirardi et al. 1995; Mauelshagen et al. 1996, 1998; Sutton and Carew 2000). Moreover, at tail SN-MN synapses, ITF declines completely to baseline by 3 h and LTF first emerges 10–15 h after 5HT, demonstrating that these phases of synaptic facilitation in the CNS are temporally discontinuous (Mauelshagen et al. 1996). These features of distinct phases of 5HT-induced synaptic facilitation are also reflected in distinct phases of Memory for sensitization induced by tail shock. 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). These three phases of Memory for sensitization in Aplysia can be mechanistically distinguished in a similar fashion as their synaptic counterparts: STM requires neither protein nor RNA synthesis, ITM requires protein but not RNA synthesis, and LTM requires both (Castellucci et al. 1989; Levenson et al. 2000; Sutton et al. 2001a). ITM and LTM can also be distinguished in the same animals based on the temporal dynamics of Memory for sensitization after training: five spaced tail shocks induces ITM that decays completely to baseline by about 3 h, several hours before the emergence of LTM (Sutton et al. 2001a). The lack of temporal overlap in these mechanistically distinct phases of Memory is experimentally advantageous, allowing for an unambiguous means for studying ITM and LTM independently. In this study, we undertook a detailed analysis of the training parameters required for the induction of ITM and LTM. We found that LTM (20–24 h after training) requires multiple, spaced (temporally distributed) trials for induction. We also found that ITM has two distinct components: an early decaying (E-ITM) phase and a late-decaying (L-ITM) phase. L-ITM (lasting >90 min), like LTM, requires multiple spaced trials for induction. E-ITM (lasting <75 min) also requires multiple training trials but can be induced by either massed or spaced patterns of training. Moreover, amounts of training that are sufficient for the induction of L-ITM and LTM when given in a spaced pattern produce only E-ITM when delivered as a massed pattern. 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. Some of the results in this paper have been previously presented in abstract form (Carew et al. 2001).
Kento Tanabe - One of the best experts on this subject based on the ideXlab platform.
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Age-Related Changes in Insulin-like Signaling Lead to Intermediate-Term Memory Impairment in Drosophila
Cell Reports, 2017Co-Authors: Kento Tanabe, Motoyuki Itoh, Ayako TonokiAbstract:Insulin and insulin-growth-factor-like signaling (IIS) plays important roles in the regulation of development, growth, metabolic homeostasis, and aging, as well as in brain functions such as learning and Memory. The temporal-spatial role of IIS in learning and Memory and its effect on age-dependent Memory impairment remain unclear. Here, we report that Intermediate-Term Memory (ITM), but not short-term Memory (STM), in Drosophila aversive olfactory Memory requires transient IIS during adulthood. The expression of Drosophila insulin-like peptide 3 (Dilp3) in insulin-producing cells and insulin receptor function in the fat body are essential for ITM. Although the expression of dilp3 decreases with aging, which is unique among dilp genes, the transient expression of dilp3 in aged flies enhances ITM. These findings indicate that ITM is systemically regulated by communication between insulin-producing cells and fat body and that age-dependent changes in IIS contribute to age-related Memory impairment.