Pavlovian Conditioning Paradigm Research Articles

Standardizing the analysis of conditioned fear in rodents: a multidimensional software approach

Data comparability between different laboratories strongly depends on the individually applied analysis method. This factor is often a critical source of variation in rodent phenotyping and has never been systematically investigated in Pavlovian fear conditioning paradigms. In rodents, fear is typically quantified in terms of freezing duration via manual observation or automated systems. While manual analysis includes biases such as tiredness or inter-personal scoring variability, computer-assisted systems are unable to distinguish between freezing and immobility. Consequently, the novel software called MOVE follows a semi-automatized approach that prefilters video sequences of interest for the final human judgment. Furthermore, MOVE allows integrating additional data sources (e.g. force-sensitive platform, EEG) to reach the most accurate and precise results. MOVE directly supports multi-angle video recordings with webcams or standard laboratory equipment. The integrated manual key logger and internal video player complement this all-in-one software solution. Calculating the interlaboratory variability of manual freezing evaluation revealed significantly different freezing scores in two out of six laboratories. This difference was minimized when all experiments were analyzed with MOVE. Applied to a genetically modified mouse model, MOVE revealed higher fear responses of CB1 deficient mice compared to their wild-type littermates after foreground context fear conditioning. Multi-angle video analysis compared to the single-camera approach reached up to 15% higher accuracy and two fold higher precision. Multidimensional analysis provided by integration of additional data sources further improved the overall result. We conclude that the widespread usage of MOVE could substantially improve the comparability of results from different laboratories.

The role of sleep and sleep deprivation in consolidating fear memories

Sleep, in particular REM sleep, has been shown to improve the consolidation of emotional memories. Here, we investigated the role of sleep and sleep deprivation on the consolidation of fear memories and underlying neuronal mechanisms. We employed a Pavlovian fear conditioning paradigm either followed by a night of polysomnographically monitored sleep, or wakefulness in forty healthy participants. Recall of learned fear was better after sleep, as indicated by stronger explicitly perceived anxiety and autonomous nervous responses. These effects were positively correlated with the preceding time spent in REM sleep and paralleled by activation of the basolateral amygdala. These findings suggest REM sleep-associated consolidation of fear memory in the human amygdala. In view of the critical participation of fear learning mechanisms in the etiology of anxiety and post-traumatic stress disorder, deprivation of REM sleep after exposure to distressing events is an interesting target for further investigation.

Cue competition effects in the planarian

The learning abilities of planarian worms (Dugesia tigrina) were assessed by using a number of Pavlovian conditioning paradigms. Experiment 1 showed that planaria were susceptible to basic conditioning in that they readily developed a conditioned response to a change in ambient luminance when it was consistently paired with an electric shock over a number of trials. In Experiment 2, the change in luminance was presented in a compound with a vibration stimulus during conditioning. Subsequent tests revealed poor conditioning of the elements compared with control groups in which the animals were conditioned in the presence of the elements alone, an instance of overshadowing. In Experiment 3, pre-training of one of the elements before compound conditioning resulted in blocking of learning about the other element. These results add to other studies that have reported cue competition effects in animal species belonging to different phyla (chordate, mollusk, arthropod), suggesting that learning in these phyla could be ruled by similar principles. The results are discussed adopting an evolutionary-comparative approach.

Reduced anticipatory dopamine responses to food in rats exposed to high fat during early development

We have previously demonstrated that exposure to high fat (HF) during early development alters the presynaptic regulation of mesolimbic dopamine (DA), and increases incentive motivation for HF food rewards. The goal of the present experiments was to examine the long-term consequences of early exposure to HF on anticipatory and consumatory nucleus accumbens (NAc) DA responses to HF food rewards. Mothers were maintained on a HF (30% fat) or control diet (CD; 5% fat) from gestation day 13 to postnatal day 22 when offspring from both diet groups were weaned and maintained on the CD until adulthood. In vivo NAc DA responses to food anticipation and consumption were measured in a Pavlovian conditioning paradigm using voltammetry in freely moving rats. HF-exposed offspring displayed reduced NAc DA responses to a tone previously paired with the delivery of HF food rewards. In an unconditioned protocol, consumatory NAc DA responses could be isolated, and were similar in HF and control offspring. These data demonstrate that exposure to HF through maternal diet during early development might program behavioral and functional responses associated with mesolimbic DA neurotransmission, thus leading to an increased HF feeding and obesity.

The Influence of Serotonin on Fear Learning

Learning of associations between aversive stimuli and predictive cues is the basis of Pavlovian fear conditioning and is driven by a mismatch between expectation and outcome. To investigate whether serotonin modulates the formation of such aversive cue-outcome associations, we used functional magnetic resonance imaging (fMRI) and dietary tryptophan depletion to reduce brain serotonin (5-HT) levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT depleted subjects compared to a non-depleted control group exhibited attenuated autonomic responses to cues indicating the upcoming of an aversive event. These results were closely paralleled by reduced aversive learning signals in the amygdala and the orbitofrontal cortex, two prominent structures of the neural fear circuit. In agreement with current theories of serotonin as a motivational opponent system to dopamine in fear learning, our data provide first empirical evidence for a role of serotonin in representing formally derived learning signals for aversive events.

Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

Role of the basolateral amygdala and NMDA receptors in higher-order conditioned fear

Laboratory rats learn to fear relatively innocuous stimuli which signal the imminent arrival of an innate source of danger, typically brief but aversive foot shock. Much is now known about the neural substrates underlying the acquisition, consolidation and subsequent expression of this fear. Rats also learn to fear stimuli which signal learned sources of danger but relatively little is known about the neural substrates underlying this form of fear. Two Pavlovian conditioning paradigms used to study this form of fear are second-order conditioning and sensory preconditioning. In second-order conditioning, rats are first exposed to a signaling relationship between one stimulus, such as a tone, and aversive foot shock, and then to a signaling relationship between a second stimulus, such as a light, and the now dangerous tone. In sensory preconditioning, these phases are reversed: rats are first exposed to a signaling relationship between the light and the tone and then to a signaling relationship between the tone and the foot shock. In both paradigms, rats exhibit fear when tested with the light. In this review paper, we describe the evidence for higher-order forms of conditioning, the conditions which promote this learning and its contents. We compare and contrast the substrates of the learning underlying second-order and sensory preconditioning fear with those known to underlie the better studied first-order conditioned fear. We conclude with some comments as to the role of higher-order processes in anxiety disorders.

Examining the sex- and circadian dependency of a learning phenotype in mice with glycine transporter 1 deletion in two Pavlovian conditioning paradigms

Behavioural characterisation of transgenic mice has been instrumental in search of therapeutic targets for the modulation of cognitive function. However, little effort has been devoted to phenotypic characterisation across environmental conditions and genomic differences such as sex and strain, which is essential to translational research. The present study is an effort in this direction. It scrutinised the stability and robustness of the phenotype of enhanced Pavlovian conditioning reported in mice with forebrain neuronal deletion of glycine transporter 1 by evaluating the possible presence of sex and circadian dependency, and its consistency across aversive and appetitive conditioning paradigms. The Pavlovian phenotype was essentially unaffected by the time of testing between the two circadian phases, but it was modified by sex in both conditioning paradigms. We observed that the effect size of the phenotype was strongest in female mice tested during the dark phase in the aversive paradigm. Critically, the presence of the phenotype in female mutants was accompanied by an increase in resistance to extinction. Similarly, enhanced conditioned responding once again emerged solely in female mutants in the appetitive conditioning experiment, which was again associated with an increased resistance to extinction across days, but male mutants exhibited an opposite trend towards facilitation of extinction. The present study has thus added hitherto unknown qualifications and specifications of a previously reported memory enhancing phenotype in this mouse line by identifying the determinants of the magnitude and direction of the expressed phenotype. This in-depth comparative approach is of value to the interpretation of behavioural findings in general.

P02-58 - The antidepressant agomelatine reduces fear long term memory but not acquisition or short term expression of fear memories

Alterations in fear learning processes may be implicated in mood disorders. Fear learning has been investigated with Pavlovian classical fear conditioning paradigms, consisting of pairing a neutral conditioned stimulus (CS), such as a tone, with an aversive unconditioned stimulus (US), such as a footshock. Upon subsequent exposure, the CS is perceived as aversive and provokes a fear response.The novel antidepressant agomelatine acts as a melatonergic receptor agonist and a 5-HT2C receptor antagonist. Its antidepressant action was demonstrated in preclinical and clinical studies. Agomelatine has also anxiolytic properties. The aim of this study was to determine how acute agomelatine treatment might differentially alter fear circuits by using auditory fear conditioning in the rat.A single pre-training injection of agomelatine (40 mg/kg intraperitoneally) significantly reduced freezing to the fear arousing CS 24 hours after training but not during training or 3 hours after training. This pattern of results is consistent with an effect on the consolidation of the fear memory. A single pre-testing injection of agomelatine had no effect on conditioned fear expression.These effects of agomelatine should be considered in relation to its antidepressant action. Agomelatine achieved a reduction of fear conditioning in a single dose, while classical SSRIs only reduced fear conditioning after chronic treatment. This finding is consistent with clinical studies suggesting a faster onset of action of agomelatine than classical SSRI treatment.

Behaviour of domestic fowl in anticipation of positive and negative stimuli

Underlying the study of animal welfare is the assumption that animals experience emotional states. Although there has been a bias towards studying negative emotions, research into positive emotions is necessary for an overall welfare assessment. The aim of the current study was to find behavioural expressions specific for anticipation of different events in domestic fowl, Gallus gallus domesticus. To this aim, we used a Pavlovian conditioning paradigm by which we induced anticipation of a positive, neutral and negative event. We investigated whether birds were able to discriminate between sound cues signalling these events with different valences and, if so, whether anticipation of different events is reflected in different behavioural responses. The birds showed a response of increased attention to all sound cues. In anticipation of the negative event, the birds showed more head movements and locomotion than in anticipation of both the neutral and positive event, possibly reflecting the aversive nature of the negative event. In anticipation of the positive event, the birds showed more comfort behaviours, such as preening and wing flapping, which have been associated with a state of relaxation. Our study shows that laying hens are able to anticipate differentially a positive, neutral and negative event announced by different sound cues. It is also the first study to identify comfort behaviours as specifically associated with anticipation of a positive event in domestic fowl. Comfort behaviours may therefore be associated with a positive emotional state in domestic fowl.

Long-Term Memory for Pavlovian Fear Conditioning Requires Dopamine in the Nucleus Accumbens and Basolateral Amygdala

The neurotransmitter dopamine (DA) is essential for learning in a Pavlovian fear conditioning paradigm known as fear-potentiated startle (FPS). Mice lacking the ability to synthesize DA fail to learn the association between the conditioned stimulus and the fear-inducing footshock. Previously, we demonstrated that restoration of DA synthesis to neurons of the ventral tegmental area (VTA) was sufficient to restore FPS. Here, we used a target-selective viral restoration approach to determine which mesocorticolimbic brain regions receiving DA signaling from the VTA require DA for FPS. We demonstrate that restoration of DA synthesis to both the basolateral amygdala (BLA) and nucleus accumbens (NAc) is required for long-term memory of FPS. These data provide crucial insight into the dopamine-dependent circuitry involved in the formation of fear-related memory.

Absence of NMDA receptors in dopamine neurons attenuates dopamine release but not conditioned approach during Pavlovian conditioning

During Pavlovian conditioning, phasic dopamine (DA) responses emerge to reward-predictive stimuli as the subject learns to anticipate reward delivery. This observation has led to the hypothesis that phasic dopamine signaling is important for learning. To assess the ability of mice to develop anticipatory behavior and to characterize the contribution of dopamine, we used a food-reinforced Pavlovian conditioning paradigm. As mice learned the cue-reward association, they increased their head entries to the food receptacle in a pattern that was consistent with conditioned anticipatory behavior. D1-receptor knockout (D1R-KO) mice had impaired acquisition, and systemic administration of a D1R antagonist blocked both the acquisition and expression of conditioned approach in wild-type mice. To assess the specific contribution of phasic dopamine transmission, we tested mice lacking NMDA-type glutamate receptors (NMDARs) exclusively in dopamine neurons (NR1-KO mice). Surprisingly, NR1-KO mice learned at the same rate as their littermate controls. To evaluate the contribution of NMDARs to phasic dopamine release in this paradigm, we performed fast-scan cyclic voltammetry in the nucleus accumbens of awake mice. Despite having significantly attenuated phasic dopamine release following reward delivery, KO mice developed cue-evoked dopamine release at the same rate as controls. We conclude that NMDARs in dopamine neurons enhance but are not critical for phasic dopamine release to behaviorally relevant stimuli; furthermore, their contribution to phasic dopamine signaling is not necessary for the development of cue-evoked dopamine or anticipatory activity in a D1R-dependent Pavlovian conditioning paradigm.

Mechanisms of attention for appetitive and aversive outcomes in Pavlovian conditioning

Different mechanisms of attention controlling learning have been proposed in appetitive and aversive conditioning. The aim of the present study was to compare attention and learning in a Pavlovian conditioning paradigm using visual stimuli of varying predictive value of either monetary reward (appetitive conditioning; 10p or 50p) or blast of white noise (aversive conditioning; 97 dB or 102 dB). Outcome values were matched across the two conditions with regard to their emotional significance. Sixty-four participants were allocated to one of the four conditions matched for age and gender. All participants underwent a discriminative learning task using pairs of visual stimuli that signalled a 100%, 50%, or 0% probability of receiving an outcome. Learning was measured using a 9-point Likert scale of expectancy of the outcome, while attention using an eyetracker device. Arousal and emotional conditioning were also evaluated. Dwell time was greatest for the full predictor in the noise groups, while in the money groups attention was greatest for the partial predictor over the other two predictors. The progression of learning was the same for both groups. These findings suggest that in aversive conditioning attention is driven by the predictive salience of the stimulus while in appetitive conditioning attention is error-driven, when emotional value of the outcome is comparable.

The Relationship Between Aversive Conditioning and Risk-avoidance in Gambling

This study investigated the relationship between aversive conditioning, heart rate variability suppression, behavioral activation system/behavioral inhibition system and risk-avoidance on the Iowa gambling task (IGT) in a nonclinical sample (29 male, 29 female, mean age = 20.7). A laboratory based Pavlovian aversive conditioning paradigm was used where a 1500 Hz tone (CS+) was followed by a burst of loud white noise (US), and a 850 Hz (CS-) tone was never followed by the US. In a subsequent extinction phase where the CS+ and CS- were presented without the US, conditioned skin conductance responses to the CS+ indicated aversive conditioning. The results showed that the participants who did not show aversive conditioning (N = 26) exhibited significantly less risk-avoidance compared to participants who did show aversive conditioning (N = 32). Regression analysis showed that among the study variables, only aversive conditioning contributed significantly to explaining variance in risk-avoidance. These results may have implications for understanding risk-taking in gambling in general, and may be a starting point understanding the role of aversive conditioning in the development and maintenance of gambling problems.

Classical conditioning of autonomic fear responses is independent of contingency awareness.

The role of contingency awareness in classical conditioning experiments using human subjects is currently under debate. This study took a novel approach to manipulating contingency awareness in a differential Pavlovian conditioning paradigm. Complex sine wave gratings were used as visual conditional stimuli (CS). By manipulating the fundamental spatial frequency of the displays, we were able to construct pairs of stimuli that varied in discriminability. One group of subjects was given an "easy" discrimination, and another was exposed to a "difficult" CS+ and CS-. A 3rd group was exposed to a stimulus that was paired with the unconditional stimulus (UCS) 50% of the time and served as a control. Skin conductance response (SCR) and continuous UCS expectancy data were measured concurrently throughout the experiment. Differential UCS expectancy was found only in the easy discrimination group. Differential SCRs were found in the easy discrimination group as well as in the difficult discrimination group, but not in the 50% contingency control. The difficult discrimination group did not exhibit differential UCS expectancy but did show clear differential SCR. These observations support a dual process interpretation of classical conditioning whereby conditioning on an implicit level can occur without explicit knowledge about the contingencies. The role of contingency awareness in classical conditioning experiments using human subjects is currently under debate. This study took a novel approach to manipulating contingency awareness in a differential Pavlovian conditioning paradigm. Complex sine wave gratings were used as visual conditional stimuli (CS). By manipulating the fundamental spatial frequency of the displays, we were able to construct pairs of stimuli that varied in discriminability. One group of subjects was given an "easy" discrimination, and another was exposed to a "difficult" CS+ and CS-. A 3rd group was exposed to a stimulus that was paired with the unconditional stimulus (UCS) 50% of the time and served as a control. Skin conductance response (SCR) and continuous UCS expectancy data were measured concurrently throughout the experiment. Differential UCS expectancy was found only in the easy discrimination group. Differential SCRs were found in the easy discrimination group as well as in the difficult discrimination group, but not in the 50% contingency control. The difficult discrimination group did not exhibit differential UCS expectancy but did show clear differential SCR. These observations support a dual process interpretation of classical conditioning whereby conditioning on an implicit level can occur without explicit knowledge about the contingencies.

Visual Perceptual Associations and Configurations

In this article we describe three types of conditioned responses of the ocular movement as a function of visual perceptual constancies, drawing points on a polygraph paper and presenting them at a determined speed. The different experimental situations allow the analysis of the appropiateness o f the words “association” and “configuration” to those and other situations of conditioning. This analysis is made in the context of application of the pavlovian conditioning paradigm to the explanation of perceptual behaviour. We also emphasise the advantages of the afore mentioned procedures with a view tooffering an alternative explanation to those which are normally given when we talk about the perception of movement.

Fear extinction in rodents.

Pavlovian conditioning paradigms have become important model systems for understanding the neuroscience of behavior. In particular, studies of the extinction of Pavlovian fear responses are yielding important information about the neural substrates of anxiety disorders, such as phobias and post-traumatic stress disorder (PTSD) in humans. These studies are germane to understanding the neural mechanisms underlying behavioral interventions that suppress fear, including exposure therapy in anxiety disorders. This unit describes detailed behavioral protocols for examining the nature and properties of fear extinction in laboratory rodents.

Stress hormone action: corticosterone determines the strength of long-term fear memory dependent on the mouse genotype

Event Abstract Back to Event Stress hormone action: corticosterone determines the strength of long-term fear memory dependent on the mouse genotype Anastasia Diamantopoulou1, 2*, Maaike Van Der Mark1, Vera Brinks1 and Melly S. Oitzl1 1 University of Leiden, Division of Medical Pharmacology, LUMC/LACDR, Netherlands 2 University of Athens, Laboratory of Biology-Biochemistry, School of Health Sciences, Greece Post-traumatic stress disorder (PTSD) is characterized by strong, uncontrolled memories of the negative event, not prone to extinction. Corticosterone, the glucocorticoid secreted in response to stress in rodents, either strengthened or weakened emotional memory processing during 4 days, depending on (i) the genetic background of the mice (C57BL/6J; BALB/c) and (ii) the spatio-temporal context of its action (Brinks et al. ExpNeurol.2009). (BALB/c: increased corticosterone-stress response and emotionality compared to C57BL/6J). Using the Pavlovian fear conditioning paradigm of alternating cue/context exposures, we assessed the persistence of fear memories (expressed as freezing). BALB/c mice exhibited enhanced fear memory compared to the C57BL/6J, which decays over time. Re-exposure to the fear-related environment on days 15 and 16 after acquisition, favored extinction of fear memory in C57BL/6J mice on days 52 and 53, which was not the case for the BALB/c. Corticosterone (250 ìg/kg, i.p.) 5 minutes before acquisition in C57BL/6J specifically facilitated memory for context related fear, opposing the extinction-favoring effects of prior re-exposure sessions. However, BALB/c mice treated with corticosterone, directly after acquisition exhibited reduced freezing during cue and context episodes on days 52 and 53, enhanced time-dependent cue fear memory decay and abolished the context-cue distinction ability. We conclude that corticosterone prior to stress in C57BL/6J mice strengthened consolidation of contextual stress-associated signals, resulting in sustained long-term fear memory: relevant for preventing the development of stress related disorders such as PTSD. Corticosterone in BALB/c mice destabilized consolidation and predominantly strongly decreased cue-related fear memories: this will allow studying therapeutic treatments. Supported by KNAW-Dobberke Stichting 2007-07(VB), IRTG NWO-DN95-420(MSO), Brain Foundation Netherlands 2008(1)-38(MSO,AD), NENS(AD). Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Diamantopoulou A, Van Der Mark M, Brinks V and Oitzl MS (2009). Stress hormone action: corticosterone determines the strength of long-term fear memory dependent on the mouse genotype. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.133 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Jun 2009; Published Online: 09 Jun 2009. * Correspondence: Anastasia Diamantopoulou, University of Leiden, Division of Medical Pharmacology, LUMC/LACDR, Leiden, Netherlands, m.oitzl@lacdr.leidenuniv.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anastasia Diamantopoulou Maaike Van Der Mark Vera Brinks Melly S Oitzl Google Anastasia Diamantopoulou Maaike Van Der Mark Vera Brinks Melly S Oitzl Google Scholar Anastasia Diamantopoulou Maaike Van Der Mark Vera Brinks Melly S Oitzl PubMed Anastasia Diamantopoulou Maaike Van Der Mark Vera Brinks Melly S Oitzl Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Exaggerated emotional behavior in mice heterozygous null for the sodium channel Scn8a (Nav1.6)

The Scn8a gene encodes the alpha-subunit of Na(v)1.6, a neuronal voltage-gated sodium channel. Mice homozygous for mutations in the Scn8a gene exhibit motor impairments. Recently, we described a human family with a heterozygous protein truncation mutation in SCN8A. Rather than motor impairment, neuropsychological abnormalities were more common, suggesting a role for Scn8a in a more diverse range of behaviors. Here, we characterize mice heterozygous for a null mutation of Scn8a (Scn8a(+/-)mice) in a number of behavioral paradigms. We show that Scn8a(+/-)mice exhibit greater conditioned freezing in the Pavlovian fear conditioning paradigm but no apparent abnormalities in other learning and memory paradigms including the Morris water maze and conditioned taste avoidance paradigm. Furthermore, we find that Scn8a(+/-)mice exhibit more pronounced avoidance of well-lit, open environments as well as more stress-induced coping behavior. Together, these data suggest that Scn8a plays a critical role in emotional behavior in mice. Although the behavioral phenotype observed in the Scn8a(+/-)mice only partially models the abnormalities in the human family, we anticipate that the Scn8a(+/-)mice will serve as a valuable tool for understanding the biological basis of emotion and the human diseases in which abnormal emotional behavior is a primary component.

Overshadowing in conditioned taste aversion or in conditioned emotional response after neonatal ventral hippocampal lesions in rats

The neonatal hippocampus lesion thought to model schizophrenia should show the same modifications in behavioural tests as other models, especially pharmacological models, namely decreased latent inhibition, blocking and overshadowing. The present study is set out to evaluate overshadowing in order to complement our previous studies, which had tested latent inhibition. “Overshadowing” refers to the decreased conditioning that occurs when the to-be-conditioned stimulus is combined with another stimulus at the conditioning stage. We used the same two Pavlovian conditioning paradigms as in our previous works, namely conditioned taste aversion (CTA) and conditioned emotional response (CER). A sweet taste overshadowed a salty conditioned stimulus, and a tone overshadowed a flashing light. Totally different stimuli were used to counter possible sensory biases. The protocols were validated with two groups of Sprague Dawley rats. The same two protocols were then applied to a cohort of rats whose ventral hippocampus had been destroyed when they were 7 days old. Only rats with extended ventral hippocampus lesions were included. The overall effect of Pavlovian conditioning was attenuated, significantly so in the conditioned emotional response paradigm, but overshadowing appeared not to be modified in either the conditioned emotional response or the conditioned taste aversion paradigm.