Search

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 concurrently in standard contextual fear conditioning (sCFC). By infusing the GABAA receptor agonist muscimol into medial prefrontal cortex (mPFC) in adolescent Long-Evans rats, the current set of experiments examined the functional role of the mPFC in each phase of the CPFE and sCFC. In the CPFE, the mPFC is necessary for the following: acquisition and/or consolidation of context memory (Experiment 1), reconsolidation of a context memory to include shock (Experiment 2), and expression of contextual fear memory during a retention test (Experiment 3). In contrast to the CPFE, inactivation of the mPFC prior to conditioning in sCFC has no effect on acquisition, consolidation, or retention of a contextual fear memory (Experiment 4). Interestingly, the mPFC is not required for acquiring a context-shock association (measured by post-shock freezing) in the CPFE or sCFC (Experiment 2b and 4). Taken together, these results indicate that the mPFC is differentially recruited across stages of learning and variants of contextual fear conditioning (CPFE versus sCFC). More specifically, separating out learning about the context and the context-shock association necessitates activation of the medial prefrontal cortex during early learning and/or consolidation.

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 disrupts reversal learning in developing rats, as reported in an earlier work by Chadman et al., but it is not known whether NMDA-receptor function within the dmSTR plays a role in this effect. In Experiment 1, reversal learning was dose-dependently impaired following bilateral dmSTR administration of MK-801 (either 2.5 or 5.0 [micro]g) only during the reversal phase relative to saline in postnatal day (P) 26 rats. In Experiment 2, separate groups of P26 rats were trained on the same reversal learning task, but were administered bilateral dmSTR infusions during acquisition only (MK-SAL), reversal only (SAL-MK), both phases (MK-MK), or neither phase (SAL-SAL). The MK-801 effect was specific to the reversal training phase. The drug did not alter acquisition of the initial discrimination. Analysis of the pattern of errors indicates that dmSTR MK-801 treatment increased perseveration of the choice response trained in acquisition. NMDA receptors in the dmSTR play a role in reversal learning in the weanling rat.

mGLuR1-absent mice exhibit ataxic cerebellar symptoms and defective long term depression (LTD) and conditioned eyeblink response. They exhibit normal cerebellar anatomy, functional excitatory synaptic transmission from parallel and climbing fibers to the Purkinje cells and normal voltage-gated Ca+ channels of Purkinje cells. Observations on the mutant mice suggest that LTD activation requires mGLuR1 and that LTD deficiency leads to defective eyeblinking and ataxic symptoms.

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, & Stanton, 2011 Neurobiology of Learning and Memory, 95(2), 190–198). Whether context learning is "incidental" or "reinforcement‐driven" may determine the ontogeny and neural systems involved (Rudy, 2009, Learning & Memory (Cold Spring Harbor, N.Y.), 16, 573–585). However, we have shown differential ontogeny of two different forms of incidental context learning, the context pre‐exposure facilitation effect (CPFE; Jablonski, Schiffino, & Stanton, 2012, Developmental Psychobiology, 54(7), 714–722), which emerges between PD 17 and 21; and object‐in‐context recognition (OiC, Ramsaran, Westbrook, & Stanton, 2016, Developmental Psychobiology, 58(7), 883–895; Ramsaran, Sanders, & Stanton, 2016, Behavioural Brain Research, 298, 37–47), which is present on PD17. We investigated whether this task‐dissociation reflects an encoding or a retention deficit, by varying the sample‐to‐testing intervals for both tasks. Experiment 1A found that PD17 rats were able to perform the OiC task after short (5 min) but not long (24 hr) sample‐to‐test intervals. Experiments 1B and 1C found that PD17 rats trained on the CPFE are able to acquire and express context‐shock associations after short but not long retention intervals. These findings suggest that pre‐weanling rats encode contexts but show poor consolidation or retrieval after longer retention intervals. [ABSTRACT FROM AUTHOR]

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 24 hr. In Experiment 1, systemic administration of the NMDAR antagonist, MK‐801, prior to conditioning disrupted retention but not post‐shock freezing during sCFC in PD31 rats. Experiment 2 replicated and extended this effect to PD17 versus PD31 rats. Consistent with Experiment 1, pre‐training MK‐801 spared post‐shock freezing but impaired retention freezing in PD31 rats. In contrast, pre‐training MK‐801 disrupted post‐shock freezing in PD17 rats, which showed no retention freezing regardless of drug. These results reveal developmental differences in the role of NMDAR activity in the acquisition versus retention of a context‐shock association during sCFC in pre‐weanling and adolescent rats. [ABSTRACT FROM AUTHOR]

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 cognitive function. Methods: Sixty‐nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid‐pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape‐flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. Results: Infants born to choline‐treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline‐treated infants showed considerable catch‐up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. Conclusions: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol‐exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory. [ABSTRACT FROM AUTHOR]

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 of memory (e.g., object, spatial, and contextual memory). However, relatively little is known about the determinants of recognition memory during development. The present study extends our recent research on the development of recognition memory by further characterizing the ontogeny of contextual recognition (Ramsaran, Westbrook, & Stanton, 2016). We report that long-term retention of object-in-context (OiC) memory emerges during early development in the rat (Experiment 1), and that performance of object-place-context (OPC), a spatial variant of the OiC task, also displays protracted development until early adolescence (Experiment 2). In addition, we examined the role of NMDA receptors (NMDARs) in contextual recognition and found that OiC memory is not dependent on NMDAR-mediated plasticity whereas performance of spatial task variants including the distal cue OiC (Ramsaran et al., 2016) and OPC tasks are NMDAR-dependent (Experiments 3 and 4). The ontogeny of contextual recognition is influenced by memory retention and spatial processing demands, which may also determine the neurobiological mechanisms supporting task performance. [ABSTRACT FROM AUTHOR]

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 available: 26 with full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 15 nonsyndromal heavily exposed (HE), and 13 controls. Using voxelwise analyses, children with FAS/PFAS showed significantly lower fractional anisotropy (FA) in four white matter (WM) regions and higher mean diffusivity (MD) in seven; three regions of FA and MD differences (left inferior longitudinal fasciculus (ILF), splenium, and isthmus) overlapped, and the fourth FA cluster was located in the same WM bundle (right ILF) as an MD cluster. HE children showed lower FA and higher MD in a subset of these regions. Significant correlations were observed between three continuous alcohol measures and DTI values at cluster peaks, indicating that WM damage in several regions is dose dependent. Lower FA in the regions of interest was attributable primarily to increased radial diffusivity rather than decreased axonal diffusivity, suggesting poorer axon packing density and/or myelination. Multiple regression models indicated that this cortical WM impairment partially mediated adverse effects of PAE on information processing speed and eyeblink conditioning. Hum Brain Mapp 37:2943-2958, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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 eyeblink classical conditioning (EBC) as a well-characterized model system to study the neural mechanisms underlying associative learning. Behavioral EBC studies in adults with alcohol use disorders and in children with fetal alcohol spectrum disorders report a clear learning deficit in these two patient populations, suggesting alcohol-related damage to the cerebellum and associated structures. Insight into the neural mechanisms underlying these learning impairments has largely stemmed from laboratory animal studies. In this mini-review, we present and discuss exemplary animal findings and data from patient and neuroimaging studies. An improved understanding of the neural mechanisms underlying learning deficits in EBC related to alcoholism and prenatal alcohol exposure has the potential to advance the diagnoses, treatment, and prevention of these and other pediatric and adult disorders. [ABSTRACT FROM AUTHOR]

The present study used the context preexposure facilitation effect (CPFE) to examine long-term retention of incidental context learning in periweanling, adolescent and adult rats. The CPFE is a variant of contextual fear conditioning in which encoding the context representation, associating this representation with shock, and expressing the context–shock association each occur on separate occasions. Experiment 1 manipulated the retention interval—1 d, 8 d, 15 d, or 22 d—between context preexposure and training with immediate shock to determine how long the encoded context could be remembered (testing always occurred 24 h following training). The other factors were age—postnatal day (PND) 24 vs 31—and training group—Preexposed to the training context (Pre) vs. an alternate context (Alt-Pre). At both ages, significantly more freezing was evident in the Pre vs. Alt Pre Groups at the 24 h, 8 d and 15 d retention intervals but not at the 22 d interval, indicating that juvenile–adolescent rats remember the context for up to 15 d. In contrast, context memory persists for 22 days in adult rats (Experiment 2); and is not evident after 24 h, 8 d, or 15 d retention intervals in PND 17 rats (Experiment 3). The present study illustrates the value of the CPFE paradigm for investigations of long-term context memory in developing rats. Implications for the neurobiology of infantile amnesia are discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT Novel object and location recognition tasks harness the rat's natural tendency to explore novelty (Berlyne, 1950) 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 objects, but only PD21 and PD26 rats recognize a novel location of a familiar object. These results suggest that novel object recognition develops before PD17, while object location recognition emerges between PD17 and PD21. Experiment 2 studied the ontogenetic profile of object location memory retention in PD21, 26, and 31 rats. PD26 and PD31 rats retained the object location memory for both 10-min and 24-hr delays. PD21 rats failed to retain the object location memory for the 24-hr delay, suggesting differential development of short- versus long-term memory in the ontogeny of object location memory. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1492-1506, 2014. [ABSTRACT FROM AUTHOR]

Background 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 regions of the brain. We used in vivo 1H magnetic resonance spectroscopy ( MRS) to examine effects of prenatal alcohol exposure on neurochemistry in this important cerebellar region. Methods MRS data from the deep cerebellar nuclei were acquired from 37 children with heavy prenatal alcohol exposure and 17 non- or minimally exposed controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa. Results Increased maternal alcohol consumption around time of conception was associated with lower N-Acetylaspartate ( NAA) levels in the deep nuclei ( r = −0.33, p < 0.05). Higher levels of alcohol consumption during pregnancy were related to lower levels of the choline-containing metabolites ( r = −0.37, p < 0.01), glycerophosphocholine plus phosphocholine (Cho). Alcohol consumption levels both at conception ( r = 0.35, p < 0.01) and during pregnancy ( r = 0.38, p < 0.01) were related to higher levels of glutamate plus glutamine (Glx). All these effects continued to be significant after controlling for potential confounders. Conclusions The lower NAA levels seen in relation to prenatal alcohol exposure may reflect impaired neuronal integrity in the deep cerebellar nuclei. Our finding of lower Cho points to disrupted Cho metabolism of membrane phospholipids, reflecting altered neuropil development with potentially reduced content of dendrites and synapses. The alcohol-related alterations in Glx may suggest a disruption of the glutamate-glutamine cycling involved in glutamatergic excitatory neurotransmission. [ABSTRACT FROM AUTHOR]

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 analysis of spatial learning and memory in adolescent sheep using several traditional T-maze tasks. Both 9- and 14-week-old lambs acquired a delayed nonmatching-to-place task, but the older lambs learned the task significantly faster. In contrast, acquisition of a matching-to-place task was significantly more difficult. Lambs, like rodents, appear to have a predisposition toward learning 'win-shift' spatial problems in a T-maze under appetitive motivation. Lambs also rapidly acquired a position habit and showed typical reversal learning curves. These findings support the use of T-maze tasks to assess behavioral outcomes in various sheep models. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 785-797, 2012 [ABSTRACT FROM AUTHOR]

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 al. [2011] Neurobiology of Learning and Memory 95(2):190-198). This study investigated this ontogenetic effect further and reports three findings: First, the CPFE is absent on PND 19 but emerges modestly in rats given exposure on PND 21. Second, the absence of the CPFE on PND 17 does not reflect inability to consolidate the context-shock association established on the training day. Lastly, the CPFE on PND 24 requires exposure to the combined features of the context. These results are the first to show that the early development of contextual fear conditioning depends on conjunctive representations and that processes underlying the CPFE begin to emerge around PND 21 in the rat. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 714-722, 2012. [ABSTRACT FROM AUTHOR]