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Ilene L Bernstein - One of the best experts on this subject based on the ideXlab platform.
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molecular signaling during Taste Aversion learning
Chemical Senses, 2007Co-Authors: Ilene L Bernstein, Ming Teng KohAbstract:Behavioral and neural assessment tools have been used to identify cellular and molecular events that occur during Taste Aversion acquisition. Studies described here include an assessment of Taste information processing and Taste-illness association using fos-like immunoreactivity (FLI) to mark populations of cells that react strongly to the Taste conditioned stimulus (CS), the illness unconditioned stimulus (US), or the pairing of CS and US. Exposure to a novel, but not a familiar, CS Taste (saccharin) was found to induce robust increases in FLI in some, but not all, brain regions previously implicated in Taste processing or Taste Aversion learning. Striking effects of Taste novelty on FLI were found in central amygdala (CNA) and insular cortex (IC) but not in basolateral amygdala (BLA), pontine parabrachial nucleus (PBN), or nucleus of the solitary tract (NTS). Of those regions responding to Taste novelty, only CNA showed significant elevations in FLI in response to the US, LiCl. In additional studies, FLI was examined after an effective training experience, novel CS-US pairing, and compared with an ineffective one, familiar CS-US pairing. After CS-US pairing, Taste novelty modulated FLI in virtually all the regions previously implicated in conditioned Taste Aversion (CTA) learning, including PBN, CNA, BLA, IC, as well as NTS. Thus, a distributed and interdependent neural CTA circuit is mapped using this method, and the use of localized lesion and inactivation studies promises to further define the functional role of structures within this circuit.
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mapping conditioned Taste Aversion associations using c fos reveals a dynamic role for insular cortex
Behavioral Neuroscience, 2005Co-Authors: Ming Teng Koh, Ilene L BernsteinAbstract:Novel Tastes are more effective than familiar Tastes as conditioned stimuli (CSs) in Taste Aversion learning. Parallel to this, a novel CS-unconditioned stimulus (US) pairing induced stronger Fos-like immunoreactivity (FLI) in insular cortex (IC), amygdala, and brainstem than familiar CS-US pairing, suggesting a large circuit is recruited for acquisition. To better define the role of IC, the authors combined immunostaining with lesion or reversible inactivation of IC. Lesions abolished FLI increases to novel Taste pairing in amygdala, suggesting a role in novelty detection. Reversible inactivation during Taste preexposure increased FLI to familiar Taste pairing in amygdala and brainstem. The difference between temporary inactivation, which blocked establishment of "safe" Taste memory, and lesions points to a dual role for IC in Taste learning.
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inhibition of protein kinase a activity during conditioned Taste Aversion retrieval interference with extinction or reconsolidation of a memory
Neuroreport, 2003Co-Authors: Ming Teng Koh, Ilene L BernsteinAbstract:The involvement of the cAMP-dependent protein kinase A (PKA) signaling pathway in protein synthesis-dependent memory consolidation has been supported by studies of fear conditioning and conditioned Taste Aversion (CTA). The present experiment examined whether inhibition of PKA activity at the time of memory retrieval impedes or promotes subsequent extinction. When Rp-cAMPS was infused into the amygdala at the time of CTA testing (retrieval), extinction was accelerated. Results confirm recent findings that stored memories become more labile when they are retrieved and extend these findings to CTA memories.
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Novel Tastes elevate c-fos expression in the central amygdala and insular cortex: implication for Taste Aversion learning.
Behavioral neuroscience, 2003Co-Authors: Ming Teng Koh, Emily E. Wilkins, Ilene L BernsteinAbstract:Taste novelty strongly modulates the speed and strength of Taste Aversion conditioning. To identify molecular signals responsive to novel Tastes, immunostaining for c-fos protein (Fos-like immunoreactivity [FLI]) was used to mark neurons that responded differentially to Taste novelty. Novel saccharin induced larger increases in FLI than familiar saccharin. This pattern was seen in central amygdala and insular cortex, but not in basolateral amygdala, parabrachial nucleus, or nucleus of the solitary tract. Other parameters known to influence Aversion learning were tested for effects on FLI. Manipulations known to reduce the strength of learning blunted the FLI response, supporting the idea that FLI marks neural pathways critical to Taste processing during acquisition, and that c-fos expression is a key transcriptional event underlying this plasticity.
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induction of a brainstem correlate of conditioned Taste Aversion expression role of the pontine parabrachial nucleus
Behavioural Brain Research, 2002Co-Authors: Matilde Lopez Grancha, Inmaculada Cubero, Todd E Thiele, Montserrat Navarro, Ilene L BernsteinAbstract:Increases in Fos-like immunoreactivity (FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) are seen following the expression of a conditioned Taste Aversion (CTA). In studies limited to behavioral assessment, the pontine parabrachial nucleus (PBN) has been demonstrated to play a critical role in the acquisition, but not the expression, of CTAs. To better define the role of the PBN in Taste Aversion learning, the present study examined the effects of PBN lesions on FLI in iNTS in animals with lesions placed either before or after CTA training. As is the case with behavioral expression of a CTA, timing of PBN lesions was found to be critical. Lesions placed prior to conditioning blocked evidence of conditioning, including both Taste rejection and FLI in iNTS. Lesions placed after conditioning, but before testing, did not interfere with either Taste rejection or FLI. These results support and extend prior claims that PBN is critical for CTA acquisition but not expression. They also demonstrate that input from PBN to iNTS is not necessary for the FLI seen there during CTA expression.
Etsuro Ito - One of the best experts on this subject based on the ideXlab platform.
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Another Example of Conditioned Taste Aversion: Case of Snails.
Biology, 2020Co-Authors: Junko Nakai, Yuki Totani, Dai Hatakeyama, Varvara E. Dyakonova, Etsuro ItoAbstract:Conditioned Taste Aversion (CTA) in mammals has several specific characteristics: (1) emergence of a negative symptom in subjects due to selective association with a Taste-related stimulus, (2) robust long-term memory that is resistant to extinction induced by repeated presentation of the conditioned stimulus (CS), (3) a very-long-delay presentation of the unconditioned stimulus (US), and (4) single-trial learning. The pond snail, Lymnaea stagnalis, can also form a CTA. Although the negative symptoms, like nausea, in humans cannot be easily observed in invertebrate animal models of CTA, all the other characteristics of CTA seem to be present in snails. Selective associability was confirmed using a sweet sucrose solution and a bitter KCl solution. Once snails form a CTA, repeated presentation of the CS does not extinguish the CTA. A long interstimulus interval between the CS and US, like in trace conditioning, still results in the formation of a CTA in snails. Lastly, even single-trial learning has been demonstrated with a certain probability. In the present review, we compare, in detail, CTA in mammals and snails, and discuss the possible molecular events in CTA.
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cerebral giant cells are necessary for the formation and recall of memory of conditioned Taste Aversion in lymnaea
Zoological Science, 2017Co-Authors: Hiroshi Sunada, Etsuro Ito, Ken LukowiakAbstract:The pond snail Lymnaea stagnalis can acquire conditioned Taste Aversion (CTA) as a long-term memory. CTA is caused by the temporal pairing of a stimulus, such as sucrose (the conditioned stimulus; CS), with another stimulus, such as electric shock (the unconditioned stimulus; US). Previous studies have demonstrated changes in both cellular and molecular properties in a pair of neurons known as the cerebral giant cells (CGCs), suggesting that these neurons play a key role in CTA. Here we examined the necessity of the pair of CGC somata for the learning, memory formation and memory recall of CTA by using the soma ablation technique. There was no difference in the feeding response elicited by the CS before and after ablation of the CGC somata. Ablation of the CGC somata before Taste-Aversion training resulted in the learning acquisition, but the memory formation was not observed 24 h later. We next asked whether memory was present when the CGC somata were ablated 24 h after Taste-Aversion training. The memory was present before performing the somata ablation. However, when we tested snails five days after somata ablation, the memory recall was not present. Together the data show that: 1) the somata of the CGCs are not necessary for learning acquisition; 2) the somata are necessary for memory formation; and 3) the somata are necessary for memory recall. That is, these results demonstrate that the CGCs function in the long-term memory of CTA in Lymnaea.
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the yerkes dodson law and appropriate stimuli for conditioned Taste Aversion in lymnaea
The Journal of Experimental Biology, 2015Co-Authors: Etsuro Ito, Miki Yamagishi, Satoshi Takigami, Manabu Sakakibara, Yutaka Fujito, Ken LukowiakAbstract:The pond snail Lymnaea stagnalis can learn conditioned Taste Aversion and then consolidate it into long-term memory (LTM). A high-voltage electric shock was used as the unconditioned stimulus, where we have previously used KCl. We varied the strength of both the conditioned and unconditioned stimuli to determine whether the so-called Yerkes-Dodson law prevailed. This is an empirical relationship between the state of arousal and LTM formation, showing that there is an optimal level of arousal leading to memory formation. However, too little or too much arousal results in poorer LTM. We found here that the most appropriate stimuli to use in Taste Aversion training in Lymnaea were a 10 mmol l(-1) sucrose solution as the conditioned stimulus and a 3 s electric shock as the unconditioned stimulus.
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increase in cyclic amp concentration in a cerebral giant interneuron mimics part of a memory trace for conditioned Taste Aversion of the pond snail
Biophysics, 2013Co-Authors: Emi Otsuka, Miki Yamagishi, Ken Lukowiak, Ryuichi Okada, Akiko Okuta, Miho Matsunaga, Etsuro ItoAbstract:Conditioned Taste Aversion (CTA) can be classically conditioned in the pond snail Lymnaea stagnalis and subsequently be consolidated into long-term memory (LTM). The neural trace that subserves CTA-LTM can be summarized as follows: A polysynaptic inhibitory postsynaptic potential recorded in the neuron 1 medial (N1M) cell in the conditioned snails as a result of activation of the cerebral giant cell (CGC) is larger and lasts longer than that in control snails. The N1M cell is ultimately activated by the CGC via the neuron 3 tonic (N3t) cell. That is, the inhibitory monosynaptic inputs from the N3t cell to the N1M cell are facilitated. The N1M and N3t cells are the members of feeding central pattern generator, whereas the CGC is a multimodal interneuron thought to play a key role in feeding behavior. Here we examined the involvement of a second messenger, cAMP, in the establishment of the memory trace. We injected cAMP into the CGC and monitored the potentials of the B3 motor neuron activated by the CGC. B3 activity is used as an index for the synaptic inputs from the N3t cell to the N1M cell. We found that the B3 potentials were transiently enlarged. Thus, when the cAMP concentration is increased in the CGC by Taste Aversion training, cAMP-induced changes may play a key role in the establishment of a memory trace in the N3t cell.
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from likes to dislikes conditioned Taste Aversion in the great pond snail lymnaea stagnalis
Canadian Journal of Zoology, 2013Co-Authors: Etsuro Ito, Ken Lukowiak, S Kojima, Manabu SakakibaraAbstract:The neural circuitry comprising the central pattern generator (CPG) that drives feeding behavior in the great pond snail (Lymnaea stagnalis (L., 1758)) has been worked out. Because the feeding behavior undergoes associative learning and long-term memory (LTM) formation, it provides an excellent opportunity to study the causal neuronal mechanisms of these two processes. In this review, we explore some of the possible causal neuronal mechanisms of associative learning of conditioned Taste Aversion (CTA) and its subsequent consolidation processes into LTM in L. stagnalis. In the CTA training procedure, a sucrose solution, which evokes a feeding response, is used as the conditioned stimulus (CS) and a potassium chloride solution, which causes a withdrawal response, is used as the unconditioned stimulus (US). The pairing of the CS–US alters both the feeding response of the snail and the function of a pair of higher order interneurons in the cerebral ganglia. Following the acquisition of CTA, the polysynaptic i...
Federico Bermudezrattoni - One of the best experts on this subject based on the ideXlab platform.
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Taste Aversion memory reconsolidation is independent of its retrieval
Neurobiology of Learning and Memory, 2012Co-Authors: Carlos J Rodriguezortiz, Israela Balderas, Paola Garciadelatorre, Federico BermudezrattoniAbstract:Reconsolidation refers to the destabilization/re-stabilization memory process upon its activation. However, the conditions needed to undergo reconsolidation, as well as its functional significance is quite unclear and a matter of intense investigation. Even so, memory retrieval is held as requisite to initiate reconsolidation. Therefore, in the present work we examined whether transient pharmacological disruption of memory retrieval impedes reconsolidation of stored memory in the widely used associative conditioning task, Taste Aversion. We found that AMPA receptors inhibition in the amygdala impaired retrieval of Taste Aversion memory. Furthermore, AMPA receptors blockade impeded retrieval regardless of memory strength. However, inhibition of retrieval did not affect anisomycin-mediated disruption of reconsolidation. These results indicate that retrieval is a dispensable condition to undergo reconsolidation and provide evidence of molecular dissociation between retrieval and activation of memory in the non-declarative memory model Taste Aversion.
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differential involvement of cortical muscarinic and nmda receptors in short and long term Taste Aversion memory
European Journal of Neuroscience, 2002Co-Authors: Ranier Gutierrez, Guillaume Ferreira, V De La Cruz, Federico BermudezrattoniAbstract:In conditioned Taste Aversion, an animal avoids a Taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short-term memory (STM) and long-term memory (LTM) of Taste Aversion in rats. Taste Aversion was induced by intraperitoneal administration of lithium chloride (a malaise-inducing drug) 15 min after experience with an unfamiliar Taste. In order to test STM and LTM of Taste Aversion, Taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new Taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the Taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during Taste-illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of Taste memory, whereas NMDA receptors participate in Taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent Taste-illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: Taste memory consolidation vs. Taste-illness association.
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in vivo effects of intracortical administration of nmda and metabotropic glutamate receptors antagonists on neocortical long term potentiation and conditioned Taste Aversion
Behavioural Brain Research, 2002Co-Authors: Martha L Escobar, Ileana Alcocer, Federico BermudezrattoniAbstract:It has been proposed that long-term potentiation (LTP), a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned Taste Aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-d-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonists CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid, 0.03 μg per hemisphere) and AP-5 (D(-)-2-amino-5-phosphonopentanoic, 2.5 μg per hemisphere) disrupt the acquisition of conditioned Taste Aversion, as well as IC-LTP induction in vivo. In contrast, administration of the metabotropic glutamate receptor antagonist MCPG ((RS)-α-methyl-4-carboxyphenylglycine, 2.5 μg per hemisphere) does not disrupt the acquisition of CTA nor IC-LTP induction. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA-dependent neocortical LTP constitute a possible mechanism for the learning-related functions performed by the IC.
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long term potentiation in the insular cortex enhances conditioned Taste Aversion retention
Brain Research, 2000Co-Authors: Martha L Escobar, Federico BermudezrattoniAbstract:Long-lasting changes in synaptic strength, such as long-term potentiation (LTP), are thought to underlie memory formation. Recent studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and retention of conditioned Taste Aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce LTP in the IC of adult rats in vivo, as well as, that blockade of N-methyl-D-aspartate (NMDA) receptors disrupts CTA and IC-LTP induction in vivo. Here, we present experimental data showing that induction of LTP in the Bla-IC projection previous to CTA training enhances the retention of this task. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying neocortical LTP may contribute to memory related functions performed by the IC.
Ken Lukowiak - One of the best experts on this subject based on the ideXlab platform.
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epicatechin increases the persistence of long term memory formed by conditioned Taste Aversion in lymnaea
The Journal of Experimental Biology, 2021Co-Authors: Ayaka Itoh, Ken Lukowiak, Yoshimasa Komatsuzaki, Minoru SaitoAbstract:ABSTRACT We examined the effects of epicatechin (Epi), a flavonoid abundant in green tea and cocoa, on long-term memory (LTM) formed following conditioned Taste Aversion (CTA) training in Lymnaeastagnalis. In CTA training, the snails learnt to avoid a food that initially they liked (i.e. sucrose). Twenty-four hours after CTA training, 67% of the trained snails showed a significant decrease in the feeding behaviour elicited by sucrose. Placing snails in the Epi solution in CTA training did not alter the percentage of snails exhibiting LTM, but it significantly increased LTM persistence. We also examined changes following Epi exposure in spontaneous activity of the cerebral giant cells (CGCs) that modulate feeding behaviour and are necessary for CTA-LTM. Our data suggest that Epi causes a decrease in CGC activity and increases LTM persistence, possibly via a GABAergic mechanism.
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cerebral giant cells are necessary for the formation and recall of memory of conditioned Taste Aversion in lymnaea
Zoological Science, 2017Co-Authors: Hiroshi Sunada, Etsuro Ito, Ken LukowiakAbstract:The pond snail Lymnaea stagnalis can acquire conditioned Taste Aversion (CTA) as a long-term memory. CTA is caused by the temporal pairing of a stimulus, such as sucrose (the conditioned stimulus; CS), with another stimulus, such as electric shock (the unconditioned stimulus; US). Previous studies have demonstrated changes in both cellular and molecular properties in a pair of neurons known as the cerebral giant cells (CGCs), suggesting that these neurons play a key role in CTA. Here we examined the necessity of the pair of CGC somata for the learning, memory formation and memory recall of CTA by using the soma ablation technique. There was no difference in the feeding response elicited by the CS before and after ablation of the CGC somata. Ablation of the CGC somata before Taste-Aversion training resulted in the learning acquisition, but the memory formation was not observed 24 h later. We next asked whether memory was present when the CGC somata were ablated 24 h after Taste-Aversion training. The memory was present before performing the somata ablation. However, when we tested snails five days after somata ablation, the memory recall was not present. Together the data show that: 1) the somata of the CGCs are not necessary for learning acquisition; 2) the somata are necessary for memory formation; and 3) the somata are necessary for memory recall. That is, these results demonstrate that the CGCs function in the long-term memory of CTA in Lymnaea.
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the yerkes dodson law and appropriate stimuli for conditioned Taste Aversion in lymnaea
The Journal of Experimental Biology, 2015Co-Authors: Etsuro Ito, Miki Yamagishi, Satoshi Takigami, Manabu Sakakibara, Yutaka Fujito, Ken LukowiakAbstract:The pond snail Lymnaea stagnalis can learn conditioned Taste Aversion and then consolidate it into long-term memory (LTM). A high-voltage electric shock was used as the unconditioned stimulus, where we have previously used KCl. We varied the strength of both the conditioned and unconditioned stimuli to determine whether the so-called Yerkes-Dodson law prevailed. This is an empirical relationship between the state of arousal and LTM formation, showing that there is an optimal level of arousal leading to memory formation. However, too little or too much arousal results in poorer LTM. We found here that the most appropriate stimuli to use in Taste Aversion training in Lymnaea were a 10 mmol l(-1) sucrose solution as the conditioned stimulus and a 3 s electric shock as the unconditioned stimulus.
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increase in cyclic amp concentration in a cerebral giant interneuron mimics part of a memory trace for conditioned Taste Aversion of the pond snail
Biophysics, 2013Co-Authors: Emi Otsuka, Miki Yamagishi, Ken Lukowiak, Ryuichi Okada, Akiko Okuta, Miho Matsunaga, Etsuro ItoAbstract:Conditioned Taste Aversion (CTA) can be classically conditioned in the pond snail Lymnaea stagnalis and subsequently be consolidated into long-term memory (LTM). The neural trace that subserves CTA-LTM can be summarized as follows: A polysynaptic inhibitory postsynaptic potential recorded in the neuron 1 medial (N1M) cell in the conditioned snails as a result of activation of the cerebral giant cell (CGC) is larger and lasts longer than that in control snails. The N1M cell is ultimately activated by the CGC via the neuron 3 tonic (N3t) cell. That is, the inhibitory monosynaptic inputs from the N3t cell to the N1M cell are facilitated. The N1M and N3t cells are the members of feeding central pattern generator, whereas the CGC is a multimodal interneuron thought to play a key role in feeding behavior. Here we examined the involvement of a second messenger, cAMP, in the establishment of the memory trace. We injected cAMP into the CGC and monitored the potentials of the B3 motor neuron activated by the CGC. B3 activity is used as an index for the synaptic inputs from the N3t cell to the N1M cell. We found that the B3 potentials were transiently enlarged. Thus, when the cAMP concentration is increased in the CGC by Taste Aversion training, cAMP-induced changes may play a key role in the establishment of a memory trace in the N3t cell.
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from likes to dislikes conditioned Taste Aversion in the great pond snail lymnaea stagnalis
Canadian Journal of Zoology, 2013Co-Authors: Etsuro Ito, Ken Lukowiak, S Kojima, Manabu SakakibaraAbstract:The neural circuitry comprising the central pattern generator (CPG) that drives feeding behavior in the great pond snail (Lymnaea stagnalis (L., 1758)) has been worked out. Because the feeding behavior undergoes associative learning and long-term memory (LTM) formation, it provides an excellent opportunity to study the causal neuronal mechanisms of these two processes. In this review, we explore some of the possible causal neuronal mechanisms of associative learning of conditioned Taste Aversion (CTA) and its subsequent consolidation processes into LTM in L. stagnalis. In the CTA training procedure, a sucrose solution, which evokes a feeding response, is used as the conditioned stimulus (CS) and a potassium chloride solution, which causes a withdrawal response, is used as the unconditioned stimulus (US). The pairing of the CS–US alters both the feeding response of the snail and the function of a pair of higher order interneurons in the cerebral ganglia. Following the acquisition of CTA, the polysynaptic i...
Christopher L. Cunningham - One of the best experts on this subject based on the ideXlab platform.
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ethanol induced conditioned Taste Aversion in 15 inbred mouse strains
Behavioral Neuroscience, 2002Co-Authors: Julie Broadbent, Kathryn J Muccino, Christopher L. CunninghamAbstract:This study used a genetic correlational strategy to characterize the neurobiological basis of ethanol's (0, 2, or 4 g/kg) aversive effects as indexed by conditioned Taste Aversion. Substantial strain differences in Taste Aversion and hypothermia were observed, but the genetic correlation between these phenotypes was not significant. However, significant genetic correlations were observed between Taste Aversion and ethanol-related behaviors measured in previous studies, including home-cage ethanol preference (r = .68) and ethanol withdrawal severity (r = -.69). Strains showing stronger Taste Aversion tended to show lower ethanol preference and higher withdrawal severity. This pattern of findings is consistent with previous studies suggesting a commonality in neurobiological mechanisms underlying these phenotypes. These results do not support the hypothesis that ethanol-induced Taste Aversion is mediated by the drug's rewarding properties.
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ethanol induced conditioned Taste Aversion in bxd recombinant inbred mice
Alcoholism: Clinical and Experimental Research, 1998Co-Authors: Fred O. Risinger, Christopher L. CunninghamAbstract:Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned Taste Aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during Taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned Taste Aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between Taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between Taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that Taste Aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter Taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned Taste Aversion. Some of these genes appear to influence Taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.
