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Unconditioned Stimulus (unconditioned + stimulus)
Selected AbstractsREM sleep: a sensitive index of fear conditioning in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Sushil K. Jha Abstract To examine the influence of conditioned fear stimuli on sleep-wake states, we recorded sleep in Sprague,Dawley rats after exposure to tones previously paired with footshock. After habituation to a recording chamber and the recording procedure, a baseline sleep recording was obtained the next day. One day later, experimental animals were exposed to shock training designed to induce conditioned fear (FC), consisting of five tone-footshock pairings. The 5-s tones (conditioned stimuli; CS) co-terminated with 1-s footshocks (unconditioned stimuli; US). The next day sleep was recorded for 4 h in the recording chamber after presentation of five CSs alone. Sleep efficiency (total sleep time/recording period) and REM sleep (REM) and non-REM (NREM) measures were determined. While sleep efficiency was not significantly changed after CS presentation, the percentage of total sleep time spent in REM (REM percentage) was reduced in the FC animals. The reduction in REM percentage in the FC animals was due to a decrease in the number of REM bouts. In a separate experiment, we repeated the procedures, except the tones and shocks were presented in an explicitly unpaired (UP) fashion. The next day, presentation of the tones increased REM percentage in the UP group. Results are discussed in terms of the decreases in REM as a response to conditioned fear, and the relevance of these findings to the sleep changes seen in post-traumatic stress disorder (PTSD). [source] Impairment of eyeblink conditioning in GluR,2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuliEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001Yasushi Kishimoto Abstract Mice lacking the glutamate receptor subunit ,2 (GluR,2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre,Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluR,2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluR,2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluR,2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci.,13, 1249,1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluR,2 and cerebellar LTD are essential for learning when there is CS,US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US. [source] Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C ,4 mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Mariko Miyata Abstract Long-term depression (LTD) at parallel fibre,Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase C,s (PLC,s). PLC,s consist of four isoforms (PLC,1,4) among which PLC,4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLC,4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre,Purkinje cell synapses and voltage-gated Ca2+ channel currents appeared normal. The mGluR1-mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1-mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLC,4 mutant mice. Wild-type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLC,4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLC,4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response. [source] Animal Foraging and the Evolution of Goal-Directed CognitionCOGNITIVE SCIENCE - A MULTIDISCIPLINARY JOURNAL, Issue 1 2006Thomas T. Hills Abstract Foraging- and feeding-related behaviors across eumetazoans share similar molecular mechanisms, suggesting the early evolution of an optimal foraging behavior called area-restricted search (ARS), involving mechanisms of dopamine and glutamate in the modulation of behavioral focus. Similar mechanisms in the vertebrate basal ganglia control motor behavior and cognition and reveal an evolutionary progression toward increasing internal connections between prefrontal cortex and striatum in moving from amphibian to primate. The basal ganglia in higher vertebrates show the ability to transfer dopaminergic activity from unconditioned stimuli to conditioned stimuli. The evolutionary role of dopamine in the modulation of goal-directed behavior and cognition is further supported by pathologies of human goal-directed cognition, which have motor and cognitive dysfunction and organize themselves, with respect to dopaminergic activity, along the gradient described by ARS, from perseverative to unfocused. The evidence strongly supports the evolution of goal-directed cognition out of mechanisms initially in control of spatial foraging but, through increasing cortical connections, eventually used to forage for information. [source] Cross-Modal transfer of the conditioned eyeblink response during interstimulus interval discrimination training in young ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2008Kevin L. Brown Abstract Eyeblink classical conditioning (EBC) was observed across a broad developmental period with tasks utilizing two interstimulus intervals (ISIs). In ISI discrimination, two distinct conditioned stimuli (CSs; light and tone) are reinforced with a periocular shock unconditioned stimulus (US) at two different CS,US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both intervals. Developmental changes in conditioning have been reported in each task beyond ages when single-ISI learning is well developed. The present study sought to replicate and extend these previous findings by testing each task at four separate ages. Consistent with previous findings, younger rats (postnatal day,PD23 and 30) trained in ISI discrimination showed evidence of enhanced cross-modal influence of the short CS,US pairing upon long CS conditioning relative to older subjects. ISI discrimination training at PD43,47 yielded outcomes similar to those in adults (PD65,71). Cross-modal transfer effects in this task therefore appear to diminish between PD30 and PD43,47. Comparisons of ISI discrimination with temporal uncertainty indicated that cross-modal transfer in ISI discrimination at the youngest ages did not represent complete generalization across CSs. ISI discrimination undergoes a more protracted developmental emergence than single-cue EBC and may be a more sensitive indicator of developmental disorders involving cerebellar dysfunction. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 647-664, 2008. [source] Amniotic fluid can act as an appetitive unconditioned stimulus in preweanling ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2007Carlos Arias Abstract Studies in humans and animals indicate that exposure to flavors in the amniotic fluid during the later gestational period may induce preferences for those flavors. Considering that during the last prenatal period the amniotic fluid contains substances that activate the opioid system, and that this system plays a critical role in the acquisition of olfactory preferences early in life, it has been hypothesized that the amniotic fluid may acquire appetitive unconditioned properties during this period. This has been tested in an experiment in which preweanling rats were exposed to alcohol odor (CS) paired or unpaired with the intraoral infusion of amniotic fluid (US) collected on gestational day 20. The pairing of these two stimuli induced an enhanced palatability of alcohol's flavor as well an increased intake of the drug. These results support the idea that amniotic fluid acquires appetitive unconditioned properties during the last days of gestation and suggest that associative mechanisms involving the amniotic fluid could be underlying odor and taste preferences acquired through fetal exposure. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 139,149, 2007. [source] Development of learned flavor preferencesDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2006Kevin P. Myers Abstract Rats, like humans, are born with only a few innate flavor preferences and aversions. Preferences retain great plasticity throughout the lifespan because they are sensitive to modification by experience. From an early age, rats can rapidly learn to prefer or avoid a flavor (conditioned stimulus, CS) that is associated with a positive or negative unconditioned stimulus (US). The US may be the mother's milk, social or thermotactile stimulation, or other food-related stimuli. Flavor-flavor learning occurs when the CS flavor is mixed with a naturally preferred (e.g., sweet) or avoided (e.g., bitter) US flavor. Flavor preferences and aversions are also produced by USs that have postoral positive (e.g., nutritious) or negative (e.g., toxic) actions. These types of learning appear to involve different behavioral and neural mechanisms as indicated by differences in conditioned responses, effective temporal parameters, resistance to extinction, and neurochemical mechanisms. New evidence indicates that flavor-nutrient preference learning can occur before weaning and influence food selection after weaning. Flavor conditioning not only affects food choice, but can also significantly increase food acceptance, that is, total consumption. Thus, from an early age, learning processes shape the feeding behavior of animals. While primarily serving an adaptive function, learning may play a role in biasing individuals towards excessive intake and weight gain. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 380,388, 2006. [source] Emergence of long-term memory for conditioned aversion in the rat fetusDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004Nadège Gruest Abstract Pregnant rats were subjected to garlic essential oil as the conditioned stimulus and 45 min later to LiCl as the unconditioned stimulus either on embryonic Days 15 and 16 (E15 and E16) or on 18 and 19 (E18 and E19). Control dams received only garlic, LiCl, or water. Progenies were tested on garlic drinking 6 weeks after the exposure to the stimuli via the mothers. In the E18 to 19 group, rats that were exposed to paired garlic,LiCl expressed a significant aversion for garlic. In the E15 to 16 group, no significant differences appeared between subgroups. These results confirm that an associative memory can be established before birth and suggests that this ability potentially emerges in a short time window of 3 days at the end of gestation. Moreover, it appears that a long-term memory can be acquired in utero and retained to be expressed postnatally when animals are autonomous. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 189,198, 2004. [source] Associative learning and memory in a chimpanzee fetus: Learning and long-lasting memory before birthDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2004Nobuyuki Kawai Abstract We tested whether a chimpanzee fetus could form an association between an extrauterine tone and vibroacoustic stimulation (VAS) using classical conditioning treatment. Two kinds of pure tone were used as the conditioned stimuli, one where a 500-Hz tone was always followed by a VAS of 80 Hz (110 gal), the unconditioned stimulus (US), and another where a 1000-Hz tone was never followed by a VAS. This treatment was repeated 156 times in total until natural labor at 233 days of gestational age. Behavioral tests on the 33rd and 58th days after birth revealed a differential response to the tones: The infant displayed an exaggerated response to the 500-Hz tone, but not to the 1000-Hz tone. Other naïve chimpanzee infants did not show any response to either tone, which suggests that a chimpanzee fetus can distinguish between tones and form an association, and that it retains such information for at least 2 months after birth. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 116,122, 2004. [source] Classical conditioning in the rat fetus: Involvement of mu and kappa opioid systems in the conditioned responseDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2002William P. Smotherman Abstract When the Embryonic Day 20 (E20) rat fetus is given a conditioning trial involving a paired presentation of an artificial nipple (the conditioned stimulus; CS) with an intraoral infusion of milk (the unconditioned stimulus; US), it shows evidence of classical conditioning when again exposed to the CS during a test trial. Specifically, the fetus shows fewer oral grasp responses (the conditioned response; CR) when continuously presented with the artificial nipple. The present study further investigated this classically conditioned reduction in oral grasping. Separate experiments (a) examined the time course of the reduction in oral grasping (Experiment 1), (b) characterized the time course of mu opioid (Experiment 2) and kappa opioid (Experiment 3) involvement in the CR, and (c) described changes in fetal behavior (Experiment 4) associated with mu and kappa opioid effects on responding to the artificial nipple. The results are discussed in terms of opioid involvement in establishing and maintaining early suckling behavior. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 104,115, 2002. DOI 10.1002/dev.10016 [source] The interaction of age and unconditioned stimulus intensity on long-trace conditioned flavor aversion in ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2002James R. Misanin Abstract To see if the neural representation of the conditioned stimulus (CS) is available to old-age rats beyond the time it is available to young adults, the intensity of the unconditioned stimulus (US) and the length of the CS,US interval were systematically varied in a trace conditioning experiment. Results indicated that increasing US intensity extends the interval over which trace conditioning is evident in old-age rats but not in young adults, suggesting that trace decay occurs more rapidly in young rats. Results were interpreted in terms of age differences in the workings of hypothesized biochemical timing mechanisms that may directly influence the ability to associate stimuli over trace intervals in conditioned taste-aversion procedures. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 131,137, 2002. DOI 10.1002/dev.10018 [source] Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Tali Kobilo Abstract The brain endocannabinoid system has been shown to play a role in memory, though the extent to which this role generalizes over different types and processes of memory is not yet determined. Here we show that the cannabinoid receptor 1 (CB1) plays differential roles in acquisition, extinction and reconsolidation of conditioned taste aversion (CTA) memory in the rat insular cortex, which contains the taste cortex. Activation of the CB1 receptor in the insular cortex inhibits acquisition and reconsolidation but not extinction, whereas blockade of the CB1 receptor promotes memory and blocks extinction of CTA, while having no apparent effect on reconsolidation. The CB1 ligands used in this study were incapable of substituting the unconditioned stimulus in CTA training. All in all, the data raise the possibility that the state of activity of the CB1 receptor in the insular cortex contributes to the encoding of hedonic valence that enters into association with taste items. [source] Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamineEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2005Amy J. Tindell Abstract Neurons in ventral pallidum fire to reward and its predictive cues. We tested mesolimbic activation effects on neural reward coding. Rats learned that a Pavlovian conditioned stimulus (CS+1 tone) predicted a second conditioned stimulus (CS+2 feeder click) followed by an unconditioned stimulus (UCS sucrose reward). Some rats were sensitized to amphetamine after training. Electrophysiological activity of ventral pallidal neurons to stimuli was later recorded under the influence of vehicle or acute amphetamine injection. Both sensitization and acute amphetamine increased ventral pallidum firing at CS+2 (population code and rate code). There were no changes at CS+1 and minimal changes to UCS. With a new ,Profile Analysis', we show that mesolimbic activation by sensitization/amphetamine incrementally shifted neuronal firing profiles away from prediction signal coding (maximal at CS+1) and toward incentive coding (maximal at CS+2), without changing hedonic impact coding (maximal at UCS). This pattern suggests mesolimbic activation specifically amplifies a motivational transform of CS+ predictive information into incentive salience coded by ventral pallidal neurons. Our results support incentive-sensitization predictions and suggest why cues temporally proximal to drug presentation may precipitate cue-triggered relapse in human addicts. [source] Trace eyeblink conditioning in decerebrate guinea pigsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Sadaharu Kotani Abstract We investigated the trace eyeblink conditioning in decerebrate guinea pigs to elucidate the possible role of the cerebellum and brainstem in this hippocampus-dependent task. A 350-ms tone conditioned stimulus was paired with a 100-ms periorbital shock unconditioned stimulus with a trace interval of either 0, 100, 250 or 500 ms. Decerebrate animals readily acquired the conditioned response with a trace interval of 0 or 100 ms. Even in the paradigm with a 500-ms trace interval, which is known to depend critically on the hippocampus in all animal species examined, the decerebrate guinea pigs acquired the conditioned response, which had adaptive timing as well as in the other paradigms with a shorter trace interval. However, it took many more trials to learn in the 500-ms trace paradigm than in the shorter trace interval paradigms, and the conditioned response expression was unstable from trial to trial. When decerebrate animals were conditioned step by step with a trace interval of 100, 250 and 500 ms, sequentially, they easily acquired the adaptive conditioned response to a 500-ms trace interval. However, the frequency of conditioned responses decreased after the trace interval was shifted from 250 ms to 500 ms, which was not observed after the shift from 100 ms to 250 ms. These results suggest that the cerebellum and brainstem could maintain the ,trace' of the conditioned stimulus and associate it with the unconditioned stimulus even in the 500-ms trace paradigm, but that the forebrain might be required for facilitating and stabilizing the association. [source] Impairment of eyeblink conditioning in GluR,2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuliEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001Yasushi Kishimoto Abstract Mice lacking the glutamate receptor subunit ,2 (GluR,2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre,Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluR,2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluR,2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluR,2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci.,13, 1249,1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluR,2 and cerebellar LTD are essential for learning when there is CS,US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US. [source] Disrupting basolateral amygdala function impairs unconditioned freezing and avoidance in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Almira Vazdarjanova Abstract Lesions of the lateral/basolateral amygdala nuclei (BLC) disrupt freezing behaviour in response to explicit or contextual cues (conditioned stimuli , CS) paired previously with footshock (unconditioned stimulus). This deficit in expression of defensive behaviour in response to conditioned stimuli is often interpreted as inability of lesioned rats to learn CS,US associations. However, findings of several studies indicate that BLC-lesioned rats can rapidly learn CS,US associations. Such findings suggest that lesioned rats can learn CS,US associations but are impaired in the expression of freezing behaviour. In the present study we report that both temporary inactivation (lidocaine) and permanent excitotoxic (NMDA) lesions of the BLC impair the unconditioned freezing and avoidance behaviours of rats in response to a novel fear-eliciting stimulus, a ball of cat hair. These findings suggest that the BLC influences the expression of freezing and avoidance behaviours, and/or that it potentiates rats' experience of fear. Along with prior evidence of spared memory for aversive learning after BLC lesions, these findings suggest that disrupted freezing to conditioned cues in BLC-lesioned rats does not necessarily reflect inability to form CS,US associations. [source] Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C ,4 mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Mariko Miyata Abstract Long-term depression (LTD) at parallel fibre,Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase C,s (PLC,s). PLC,s consist of four isoforms (PLC,1,4) among which PLC,4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLC,4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre,Purkinje cell synapses and voltage-gated Ca2+ channel currents appeared normal. The mGluR1-mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1-mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLC,4 mutant mice. Wild-type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLC,4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLC,4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response. [source] Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal-induced c-fos expression in nucleus accumbensEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Sarah J. Dunworth Abstract Flumazenil (20 mg/kg, i.p.)-precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21-day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c-fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli. [source] Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in miceHIPPOCAMPUS, Issue 4 2005Ilga Misane Abstract Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl- D -aspartate (NMDA) receptors in the dorsal hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1,45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15,30-s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits. © 2005 Wiley-Liss, Inc. [source] Consolidation of CS and US representations in associative fear conditioningHIPPOCAMPUS, Issue 5 2004Paul W. Frankland Abstract Much attention has been paid to the associative processes that are necessary to fuse together representations of the various components of an episodic memory. In the present study, we focus on the processes involved in the formation of lasting representations of the individual components that make up a fear-conditioning episode. In one-trial contextual fear conditioning experiments, weak conditioning to context occurs if the shock is delivered immediately following placement of the animal in a novel conditioning apparatus, a phenomenon known as the immediate shock deficit. We show that the immediate shock deficit in mice may be alleviated by pre-exposure to either the context or shock. In using this approach to temporally dissect a contextual fear-conditioning task into its constituent representational and associative processes, we are able to examine directly the processes that are important for formation of lasting representations of the context conditioned stimulus (CS) or unconditioned stimulus (US). Our data indicate that the formation of a lasting representation of the context or shock engages protein synthesis-dependent processes. Furthermore, genetic disruption of cAMP-responsive element binding protein (CREB), a transcription factor that regulates the synthesis of new proteins required for long-term memory, disrupts the formation of lasting context memories. We go on to show that the stress hormone epinephrine modulates the consolidation of a context memory, and reverses consolidation deficits in the CREB-deficient mice. Finally we show that disrupting either NMDA or calcium/calmodulin-dependent kinase II (CaMKII) function impairs consolidation of context memories. Together, these data suggest that this approach is particularly suited for the characterization of molecular and cellular processes underlying the formation of stimulus representations. © 2004 Wiley-Liss, Inc. [source] Conditioning of stress in Nile tilapiaJOURNAL OF FISH BIOLOGY, Issue 4 2004P. S. A. Moreira A Pavlovian conditioning paradigm was used to induce a connection between a conditioned stimulus, light (CS), associated with an unconditioned stimulus, confinement (US) in Nile tilapia Oreochromis niloticus, which resulted in a conditioned endocrine response (CR) to the CS alone manifested as an increase in plasma cortisol. Individual isolated Nile tilapia were submitted for 10 days to the conditioning treatment consisting of turning on a light (CS) for 1 min with subsequent 30 min confinement (US). On the 10th day of the experiment, plasma cortisol was not increased when fish were subjected to no handling at all, or only light, or even a daily stressor for the 9 days. On the other hand, at the 10th day cortisol was significantly increased only when light was presented either with or without pairing with the stressor. These results confirmed that the cue, light (CS), was not stressful in itself, but when given as the CS in the absence of the US post conditioning the hypothalamus,pituitary,interrenal axis was activated. Therefore, it was concluded that memory of a previous experience with a stressor can be recalled by a conditioned stimulus and induce stress, which is the first demonstration of a memory-induced stress in fishes. [source] A Post-ischaemic Single Administration of Galanthamine, a Cholinesterase Inhibitor, Improves Learning Ability in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2000A. I. ILIEV Transient forebrain ischaemia is widely observed in clinical practice. We have examined the effect of a single administration of the Cholinesterase inhibitor galanthamine (2 mgkg,1, i.p.) 25 min after reperfusion in male Sprague-Dawley rats (180 ± 20 g) after a 20-min common carotid artery occlusion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordination or muscle tonus of the rats treated with or without galanthamine as assessed by the rota-rod test. Learning ability was examined using the shuttle-box test, evaluating the latency time and the number of errors for six days in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the non-ischaemic rats and with the ischaemic animals administered galanthamine (P< 0.05). Similar results were obtained when counting the number of errors (failure to cross the cage during conditioned or unconditioned stimulus). The monitoring of body temperature during the first 12-h post-ischaemia did not show any significant difference between the groups. The data showed a beneficial effect of galanthamine on the recovery of learning ability when administered once only post-ischaemia. This suggests a direct effect on the early pathologic mechanisms of CNS damage. Cholinesterase inhibitors may prove useful in the early clinical treatment of ischaemic conditions. [source] Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol IntoxicationALCOHOLISM, Issue 5 2002Ricardo M. Pautassi Background: Infant rats quickly learn to avoid a sensory cue paired with alcohol as an unconditioned stimulus, particularly when the drug reaches peak blood concentrations. In this study, a tactile cue paired with the onset of alcohol intoxication preceded subsequent presentations of a gustatory conditioned stimulus (CS). The goal was to address the possibility of differential conditioning depending on when stimuli were introduced during the course of the toxic state. Methods: In experiment 1, rat pups received sequential presentations of a salient texture (sandpaper) and a gustatory cue (saccharin) while intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture location tests and saccharin intake assessments were then performed. A third modality of assessment was defined by a saccharin intake test while pups simultaneously experienced sandpaper. In experiment 2, alcohol-mediated conditioning was followed by tests similar to those of experiment 1, but after pups were re-exposed to either the tactile CS or the alcohol-unconditioned stimulus. Results: Conditioned taste aversions, due to pairing saccharin and the later stage of alcohol intoxication, were reliably established in both experiments. Also in both experiments, this excitatory aversive response was dramatically inhibited when the association between the texture CS and the earlier stage of alcohol intoxication was activated. There were no indications of conditioned motor responses to the tactile CS that might compete with intake behavior of saccharin or distort measurement of an appetitive memory derived from pairing the texture and the earlier stage of intoxication. Conclusions: Rat pups' expression of an association between a taste signaling aversive consequences of alcohol was eliminated by the presence of a tactile stimulus that originally had signaled the absence of aversive consequences of alcohol intoxication. The results suggest the interaction of inhibitory and excitatory conditioning involving the aversive properties of alcohol. [source] Ethanol as a Reinforcer in the Newborn's First Suckling ExperienceALCOHOLISM, Issue 3 2001Sarah J. Cheslock Background: Recent evidence suggests that human infants prefer alcohol-flavored milk when fed through a bottle. Animal models also indicate a surprising predisposition for neonatal and infant rats to voluntarily and willingly ingest ethanol. These findings suggest high susceptibility to the reinforcing properties of ethanol early in ontogeny. Methods: A surrogate nipple technique,a highly effective tool for investigation of the reinforcing properties of different fluids,was applied in the present study. Tests of ethanol reinforcement were accomplished in terms of two basic paradigms of Pavlovian conditioning. In one paradigm, the conditioned stimulus (CS) was the surrogate nipple, and in the other, the CS was a novel odor. Results: Newborn rats showed sustained attachment to the nipple providing 5% ethanol, and later reproduced this behavioral pattern toward the empty nipple (CS alone). Ingestion of ethanol yielding appetitive reinforcement was accompanied by detectable blood alcohol concentrations, with most in the range of 20,30 mg/dl. The reinforcing efficacy of ethanol was also confirmed in the classical olfactory conditioning paradigm: following pairing with intraoral ethanol infusions, the odor (CS) alone elicited sustained attachment to an empty nipple. Females showed better olfactory conditioning with low concentrations of ethanol, whereas males were effectively more conditioned to high concentrations. Although there were no reinforcing consequences of intraperitoneally injected ethanol [as an unconditioned stimulus (US)] when a neutral odor was the CS, when paired with ingestion of water from a nipple, the injection of ethanol had a reinforcing effect. Conclusions: The present series of experiments revealed ethanol reinforcement in the newborn rat. Two varieties of Pavlovian conditioning established that ethanol can serve as an effective US, and hence reinforcer, in such a way as to increase the approach and responsiveness toward stimuli paired with that US, indicating appetitive reinforcement. [source] | |||||||||||||