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September 2001 - present
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Publications (180)
The present study examined the effects of the muscarinic acetylcholine receptor (mAChR) antagonist, scopolamine, on standard contextual fear conditioning (sCFC). It compared effects of the drug on acquisition (post-shock freezing) versus 24-hr retention of a context-shock association acquired after one or three pairings of a context with unsignaled...
The Context Preexposure Facilitation Effect (CPFE) is a variant of contextual fear conditioning in which learning about the context, acquiring a context-shock association, and retrieval of this association occur separately across three phases (context preexposure, immediate-shock training, and retention). We have shown that prefrontal inactivation...
The article reviews our studies of contextual fear conditioning (CFC) in rats during a period of development---Postnatal Day (PND) 17-33---that represents the late-infant, juvenile, and early-adolescent stages. These studies seek to acquire ‘systems level’ knowledge of brain and memory development and apply it to a rodent model of Fetal Alcohol Spe...
The current study further examined the effect of the muscarinic acetylcholine antagonist, scopolamine, on the Context Preexposure Facilitation Effect (CPFE; Robinson-Drummer, Dokovna, Heroux, & Stanton, 2016). In the CPFE, context representations formed during the preexposure phase are retrieved and associated with immediate shock during the traini...
Context learning in postnatal day (PD) 16–18 rats has been taken by Revillo, Cotella, Paglini, and Arias (2015, Physiology & Behavior, 148, 6–21) to challenge the view that the ontogeny of contextual learning is related to the development of the hippocampal system (Rudy, 1993, Behavioral Neuroscience, 107(5), 887–891; Schiffino, Murawski, Rosen, &...
The ontogeny and NMDA‐receptor (NMDAR) mechanisms of context conditioning were examined during standard contextual fear conditioning (sCFC) – involving context and context‐shock learning in the same trial – as a comparison with our previous reports on the Context Preexposure Facilitation Effect (CPFE), which separates these two types of learning by...
Neonatal ethanol exposure during the third trimester equivalent of human pregnancy in the rat significantly impairs hippocampal and prefrontal neurobehavioral functioning. Postnatal day [PD] 4-9 ethanol exposure in rats disrupts long-term context memory formation, resulting in abolished post-shock and retention test freezing in a variant of context...
Fetal alcohol exposure leads to severe disruptions in learning and memory involving the hippocampus and prefrontal cortex in humans. Animal model research on FASD has documented impairment of hippocampal neuroanatomy and function but animal studies of cognition involving the prefrontal cortex are sparse. We have found that a variant of contextual f...
The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which learning about the context (preexposure) and associating the context with a shock (training) occur on separate occasions. The CPFE is sensitive to a range of neonatal alcohol doses (Murawski & Stanton, 2011). The current study examined the impac...
In standard contextual fear conditioning (sCFC), learning of the context and formation of the context-shock association occur in the same training session whereas in the context preexposure facilitation effect (CPFE) learning the context (preexposure) and the context-shock association (training) are separated by 24 hours. In both procedures conditi...
Background:
We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and...
The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which acquisition of the contextual representation and association of the retrieved contextual memory with an immediate foots-hock are separated by 24hrs. During the CPFE, learning- related expression patterns of the early growth response -1 gene (Egr...
The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated into three distinct phases (context preexposure, immediate-shock training, and retention). The current study...
The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated into three distinct phases. In contrast, learning about the context and the context-shock association happens...
Since the seminal report on novel object recognition in the rat (Ennaceur & Delacour, 1988), novelty recognition paradigms have become increasingly prevalent in learning and memory research. Novelty recognition tasks do not require extensive training or complex behaviors, and thus are especially suitable for studying the ontogeny of various forms o...
Prenatal alcohol exposure has been linked to a broad range of developmental deficits, with eyeblink classical conditioning (EBC) among the most sensitive endpoints. This fMRI study compared EBC-related brain activity in 47 children with fetal alcohol syndrome (FAS), partial FAS (PFAS), heavily exposed (HE) non-syndromal children, and healthy contro...
Fetal alcohol spectrum disorders comprise the spectrum of cognitive, behavioral, and neurological impairments caused by prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) was performed on 54 children (age 10.1 ± 1.0 years) from the Cape Town Longitudinal Cohort, for whom detailed drinking histories obtained during pregnancy are availab...
The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which context learning, context-shock association, and expression of context conditioning occur in 3 separate phases-preexposure, training, and testing. During the preexposure phase, the CPFE is disrupted by hippocampal NMDA receptor blockade in juven...
The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated. The current study investigated the involvement of NMDA receptors in contextual fear acquisition, retention,...
Alcoholism is a debilitating disorder that can take a significant toll on health and professional and personal relationships. Excessive alcohol consumption can have a serious impact on both drinkers and developing fetuses, leading to long-term learning impairments. Decades of research in laboratory animals and humans have demonstrated the value of...
Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FAS...
Novel object and location recognition tasks harness the rat's natural tendency to explore novelty (Berlyne, ) to study incidental learning. The present study examined the ontogenetic profile of these two tasks and retention of spatial learning between postnatal day (PD) 17 and 31. Experiment 1 showed that rats ages PD17, 21, and 26 recognize novel...
This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimu...
Prenatal alcohol exposure has been linked to impairment in cerebellar structure and function, including eyeblink conditioning. The deep cerebellar nuclei, which play a critical role in cerebellar-mediated learning, receive extensive inputs from brain stem and cerebellar cortex and provide the point of origin for most of the output fibers to other r...
Neonatal alcohol exposure impairs cognition and learning in adulthood and permanently damages the hippocampus. Wheel running (WR) improves hippocampus-assodated learning and memory and increases the genesis and survival of newly generated neurons in the hippocampal dentate gyrus. WR significantly increases proliferation of newly generated dentate g...
Seventeen-day-old rat pups received intraoral infusions of two novel flavors, coffee (0.625% w/v Sanka, decaffeinated) and saccharin (0.5% w/v), of which one (CS+) was paired with a 0.75% body weight, i.p. injection of 0.4 M LiCl, and the other (CS−) was presented alone. On the following day, two more infusion tests were conducted to determine inta...
Evidence of the partial reinforcement acquisition effect (PRAE), faster running after partial reinforcement than after continuous reinforcement in the start and run segments coupled with slower running in the goal segment of a straight-alley runway, was obtained in preweanling (18-20 days of age) and young adult (52-54 days of age) rats. While pres...
We examined developmental changes in the reversal of a learned discrimination in an olfactory conditioning paradigm in three experiments. Preweanling rats were exposed to an odor (CS+) paired with footshock and a different odor (CS−) that was explicitly unpaired with footshock. The rats were then immediately tested for their preference between the...
In rodents, voluntary exercise and environmental complexity increases hippocampal neurogenesis and reverses spatial learning and long-term potentiation deficits in animals prenatally exposed to alcohol. The present experiment extended these findings to neonatal alcohol exposure and to delay, trace, and contextual fear conditioning. Rats were admini...
The context preexposure facilitation effect (CPFE) is a variant of context fear conditioning in which context preexposure facilitates conditioning to immediate foot shock. Learning about context (preexposure), associating the context with shock (training), and expression of context fear (testing) occur in successive phases of the protocol. The CPFE...
Alcohol exposure on postnatal days (PND) 4-9 in the rat adversely affects hippocampal anatomy and function and impairs performance on a variety of hippocampus-dependent tasks. Exposure during this developmental window reveals a linear relationship between alcohol dose and spatial learning impairment in the context preexposure facilitation effect (C...
A major advantage of sheep models in experimental studies of neurodevelopmental disorders (e.g., with prenatal neurotoxicant exposure) is that the equivalent of all three trimesters of human brain development occurs in sheep entirely in utero. However, studies of learning and memory in sheep are limited. The goal of this study was to extend the ana...
The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which context learning and context-shock associations occur on separate occasions. The CPFE with an immediate shock emerges between Postnatal Day (PND) 17 and 24 in the rat and depends on hippocampal NMDA-receptor function in PND 24 rats (Schiffino et...
Classical eyeblink conditioning has been used to assess learning and memory impairments in both humans and animal model studies of fetal alcohol spectrum disorders (FASD). Gestational exposure to alcohol in humans and its equivalent in rats severely impairs various eyeblink conditioning tasks, but less is known about how these effects are influence...
This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimu...
Rats exposed to a high binge-like dose of alcohol over postnatal days (PD) 4-9 show reductions in CA1 pyramidal cells and impairments on behavioral tasks that depend on the hippocampus. We first examined hippocampal c-Fos expression as a marker of neuronal activity in normally developing rats following different phases of the context preexposure fa...
Developmental alcohol exposure can permanently alter brain structures and produce functional impairments in many aspects of behavior, including learning and memory. This study evaluates the effect of neonatal alcohol exposure on adult neurogenesis in the dentate gyrus of the hippocampus and the implications of such exposure for hippocampus-dependen...
Background:
Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific targe...
Identification of children with fetal alcohol spectrum disorders (FASD) is difficult because information regarding prenatal exposure is often lacking, a large proportion of affected children do not exhibit facial anomalies, and no distinctive behavioral phenotype has been identified. Castellanos and Tannock have advocated going beyond descriptive s...
Background:
Alcohol exposure in the rat on postnatal days (PD) 4 to 9 is known to partially damage the hippocampus and to impair hippocampus-dependent behavioral tasks. We previously reported that PD4 to 9 alcohol exposure eliminated the context preexposure facilitation effect (CPFE) in juvenile rats, a hippocampus-dependent variant of contextual...
Contextual fear conditioning emerges around post-natal day (PD) 23 in the rat. This is thought to reflect hippocampus-dependent conjunctive learning, which binds the individual features of the context into a unified representation (Rudy, 1993). However, context conditioning can also be supported by hippocampus-independent, feature-based simple asso...
Classical eyeblink conditioning (EBC) involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Impairment of EBC has been demonstrated in studies of alcohol-exposed animals and in children exposed prenatally at heavy levels.
Fetal alcohol syndrome (FAS) was diagnosed by expert dysm...
Long-Evans rats were trained on spatial delayed alteration (SDA) in a T-maze following medial prefrontal cortical (mPFC) infusions of different doses of the noncompetitive NMDA-receptor antagonist, MK-801 (.125 microl; .25 microl; or .25 microlsaline, bilaterally), on postnatal day (PND) 19, 26, or 33. Pups trained on PND 19 showed almost no learni...
Neonatal ethanol exposure in the rat is known to partially damage the hippocampus, but such exposure causes only modest or inconsistent deficits on hippocampus-dependent behavioral tasks. This may reflect variable sensitivity of these tasks or residual function following partial hippocampal injury. The context preexposure facilitation effect (CPFE)...
Several executive functions rely on the medial prefrontal cortex (mPFC) in the rat. Aspiration and neurotoxic lesions of the mPFC impair reversal learning in adult rats. Systemic administration of MK-801, an NMDA-receptor antagonist, impairs T-maze reversal learning in weanling rats but the role of mPFC NMDA-receptor antagonism in this effect is no...
Although contextual fear conditioning emerges later in development than explicit-cue fear conditioning, little is known about the stimulus parameters and biological substrates required at early ages. The authors adapted methods for investigating hippocampus function in adult rodents to identify determinants of contextual fear conditioning in develo...
Systemic administration of MK-801, an NMDA-receptor antagonist, impairs reversal learning in weanling rats [Chadman, K.K., Watson, D.J., & Stanton, M.E. (2006). NMDA-receptor antagonism impairs reversal learning in developing rats. Behavioral Neuroscience, 120(5), 1071–1083]. The brain systems responsible for this effect are not known in either adu...
Two experiments examined the effect of the noncompetitive NMDA receptor antagonist, dizocilpine maleate (MK-801), on spatial working memory during development. Rats were trained on spatial delayed alternation (SDA) in a T-maze after ip administration of 0.06 mg/kg MK-801, 0.1 mg/kg MK-801, or saline on postnatal days (P) P23 and P33 (Experiment 1),...
The striatum plays a major role in both motor control and learning and memory, including executive function and "behavioral flexibility." Lesion, temporary inactivation, and infusion of an N-methyl-d-aspartate (NMDA)-receptor antagonist into the dorsomedial striatum (dmSTR) impair reversal learning in adult rats. Systemic administration of MK-801 d...
This chapter reviews the developmental studies of eyeblink conditioning in rodents and humans that have been pursued from a multiple memory systems perspective. It extends previous summaries of the ontogeny of eyeblink conditioning in humans and in rodents, including previous rodent research on multiple memory systems. Past and current views of mul...
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 ide...
Rats exposed to valproic acid (VPA) on gestational day 12 (GD12) have been advanced as a rodent model of autism [Arndt TL, Stodgell, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005;23: 189-99.]. These rats show cerebellar anomalies and alterations in eyeblink conditioning that are associated with autism. Autistic humans and VPA-exposed...
Alcohol consumption in neonatal rats produces cerebellar damage and is widely used to model 3rd-trimester human fetal alcohol exposure. Neonatal "binge-like" exposure to high doses of alcohol (5 g/kg/day or more) impairs acquisition of eyeblink classical conditioning (EBC), a cerebellar-dependent Pavlovian motor learning task. We have recently foun...
Classical conditioning of eyeblink responses has been one of the most important models for studying the neurobiology of learning, with many comparative, ontogenetic, and clinical applications. The current study reports the development of procedures to conduct eyeblink conditioning in preweanling lambs and demonstrates successful conditioning using...
Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferio...
Background:
Neonatal alcohol consumption in rats is widely used to model cerebellar injury arising from 3rd-trimester human fetal alcohol exposure. Binge alcohol exposure of 5 g/kg/day or more over postnatal days (PD) 4 to 9 in rats damages the cerebellum and consequently impairs classical eyeblink conditioning (EBC). The present study sought to i...
This article summarizes the proceedings of a symposium organized by Mark Stanton and Pamela Hunt and presented at the annual meeting of the International Society for Developmental Psychobiology. The purpose of the symposium was to review recent advances in neurobiological and developmental studies of fear and eyeblink conditioning with the hope of...
Fear conditioning, including variants such as delay and trace conditioning that depend on different neural systems, is widely used to behaviorally characterize genetically altered mice. We present data from three strains of mice, C57/BL6 (C57), 129/SvlmJ (129), and a hybrid strain of the two (F(1) hybrids), trained on various versions of a trace fe...
Binge-like ethanol exposure on postnatal days (PD) 4-9 in rodents causes cerebellar cell loss and impaired acquisition of conditioned responses (CRs) during "short-delay" eyeblink classical conditioning (ECC), using optimal (280-350 ms) interstimulus intervals (ISIs). We extended those earlier findings by comparing acquisition of delay ECC under tw...
Discrimination and reversal of the classically conditioned eyeblink response depends on cerebellar-brainstem interactions with the hippocampus. Neonatal "binge" exposure to alcohol at doses of 5 g/kg/day or more has been shown to impair single-cue eyeblink conditioning in both weanling and adult rats. The present study exposed neonatal rats to acut...
Offspring of rats exposed to valproic acid (VPA) on gestational day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases . Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning and i...
Discrimination of the eyeblink conditioned response (CR) between conditioned stimuli (CSs) of different durations and modalities was examined across development in rats. Interstimulus interval (ISI) discrimination was evident at Postnatal Days 23-34 in Experiment 1, and earlier CR peak latencies and enhanced CR amplitudes were seen to the long CS i...
Four experiments examined the effect of dizocilpine maleate (MK-801), a noncompetitive N-methyl-Daspartate (NMDA) receptor antagonist, on reversal learning during development. On postnatal days (PND) 21, 26, or 30, rats were trained on spatial discrimination and reversal in a T-maze. When MK-801 was administered (intraperitoneally) before both acqu...
The current study established a procedure to evaluate the capability of rats on postnatal days (PND) 21, 26, and 30 to perform a spatial serial reversal task using a T-maze. Training consisted of an acquisition session followed by a series of six reversal sessions. To examine the role of proactive interference in the serial reversal effect, the poi...
A one and a half day workshop on behavioral testing was conducted in order to discuss experimental procedures and practices that may help enhance the utility of behavioral data as a reliable index of neurotoxicity and in the safety evaluation of chemical substances. The workshop was open to participation by all sectors of the neuroscience community...
The present study established an effective procedure for studying spatial conditional discrimination learning in juvenile rats using a T-maze. Wire mesh located on the floor of the maze as well as a second, identical T-maze apparatus served as conditional cues which signaled whether a left or a right response would be rewarded. In Experiment 1, con...
Reversal of discrimination learning is influenced by manipulation of the training context. In adult and developing rats, contextual changes made between acquisition and reversal aid the learning of the new discrimination, possibly by serving to release proactive interference from the originally acquired discrimination (M. E. Bouton & D. C. Brooks,...
The impact of premature birth on associative learning was evaluated using simple delay eyeblink conditioning in which a tone conditional stimulus was paired with an air puff unconditional stimulus. Fourteen preterm (28–31 weeks gestation) and 11 full-term infants completed at least 3 conditioning sessions, 1 week apart, at 5 months of age (correcte...
The ontogeny of associative learning in delay (750-ms conditional stimulus [CS], 650-ms interstimulus interval [ISI]), long-delay (1,350-ms CS, 1,250-ms ISI), and trace (750-ms CS, 500-ms trace interval, 1,250-ms ISI) eyeblink conditioning was examined in 5-month-old human infants and adults. Infants and adults showed different acquisition rates bu...
The ontogeny of associative learning in delay (750-ms conditional stimulus [CS], 650-ms interstimulus interval [ISI]), long-delay (1,350-ms CS, 1,250-ms ISI), and trace (750-ms CS, 500-ms trace interval, 1,250-ms ISI) eyeblink conditioning was examined in 5-month-old human infants and adults. Infants and adults showed different acquisition rates bu...
The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 18. Controls rece...
Associative learning was evaluated in human infants with simple delay classical eyeblink conditioning. A tone conditioned stimulus (CS) was paired with an airpuff unconditioned stimulus (US) at three different delay intervals (250, 650, and 1,250 ms). Independent groups of healthy, full-term 5-month-old human infants were assigned to these three pa...
The effects of bilateral hippocampal aspiration lesions on later acquisition of eyeblink conditioning were examined in developing Long-Evans rat pups. Lesions on postnatal day (PND) 10 were followed by evaluation of trace eyeblink conditioning (Experiment 1) and delay eyeblink conditioning (Experiment 2) on PND 25. Pairings of a tone conditioned st...
Several reports have indicated that polychlorinated biphenyls (PCB) altered development of biogenic amine systems in the brain, impaired behavioral performances, and disrupted maturation of the thyroid axis. The current study examines whether these developmental effects of PCB are correlated. Timed-pregnant Long-Evans rats were gavaged with the PCB...
