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Recent advances in computing technologies have enabled the development of low-cost, compact weather and air quality monitors. The U.S. federally funded Array of Things (AoT) project has deployed more than 140 such sensor nodes throughout the City of Chicago. This paper combines a year's worth of AoT sensor data with household data collected from 450 elderly Chicagoans in order to explore the feasibility of using previously unavailable data on local environmental conditions to improve traditional neighborhood research. Specifically, we pilot the use of AoT sensor data to overcome limitations in research linking air pollution to poor physical and mental health and find support for recent findings that exposure to pollutants contributes to both respiratory and dementia-related diseases. We expect that this support will become even stronger as sensing technologies continue to improve and more AoT nodes come online, enabling additional applications to social science research where environmental context matters.
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Early life stress enhances memory for Pavlovian fear conditioning. Stress enhancements on fear conditioning following early weaning, however, have yet to be studied in periweaning rats. Early weaning is a relevant animal model for human early life trauma, and Pavlovian fear conditioning is useful for identifying links between stress-induced developmental changes and behavior. We hypothesized that early weaning-on postnatal day (P)15-would lead to higher levels of conditional freezing relative to rats weaned later in life. Periweaning rats were trained with a discrete conditional stimulus (CS) and a shock unconditional stimulus (US), and tested 1 or 15 days later. Enhanced retention was observed in early weaned rats receiving forward paired CS-US training in Experiment 1, though this did not replicate in the second experiment. Despite overall enhancements in early weaned rats in Experiment 1, infantile amnesia effects were not overcome in young rats tested 15 days after training. Enhanced freezing levels in early weaned rats were not observed in subjects receiving unpaired CS, US training, and sensitivity to the US was not different due to age at weaning. Potential mechanisms underlying weaning-related enhancements and considerations for future studies including the role of social transmission of fear information are discussed.
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Condicionamiento Clásico , Miedo , Animales , Humanos , Ratas , DesteteRESUMEN
Modern nonhuman animal research on the rapid forgetting of memories formed early in life-often termed "infantile amnesia"-has focused on neurobiological changes occurring between learning and retention testing to explain age differences in memory. Developmental differences in initial learning have received less attention as a contributing factor to infantile amnesia effects. The present study identifies conditions under which associative learning and memory are comparable between pre and postweaning rats across multiple training-testing intervals. Postnatal day (P) 17-18 or P24-25 littermates were trained with white noise conditional stimuli (CSs) alone, forward-paired, or explicitly unpaired with floor shock unconditional stimuli (USs), and tested for retention at intervals ranging between 5 min and 15 days later. Findings from within- and across-institution replications revealed that age differences in CS freezing were influenced by (a) the associative nature of the CS and US at training, (b) the number of CS, US presentations at training, and (c) the interval between training and testing. Rats trained on P17 or 18 displayed robust retention comparable to rats trained on P24 or 25 only when training in younger rats involved additional forward-paired CS-US presentations. Poor long-term retention observed at multiple training-testing intervals in rats trained on P17 or 18 was overcome with many additional forward-paired CS-US presentations at training. Conditions necessary for appropriate developmental comparisons of learning and memory relevant to the future neurobiological studies are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Condicionamiento Clásico , Miedo , Animales , RatasRESUMEN
Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory, though nothing is known regarding developmental differences in retention between periweanling and adult rats. The present study examined retention of eyeblink conditioning in periweanling (postnatal day 24 at the start of training) and adult rats 1, 7, or 28 days after acquisition. Retention was assessed by (1) a conditional stimulus (CS)-alone test session followed by (2) CS-unconditional stimulus (US) reacquisition tests. Conditional response (CR) levels at acquisition were comparable in most respects between ages, and robust CR levels were present at the start of retention tests for both ages in the 1 day group, with CR percentages at block 1 of reacquisition higher in periweanlings relative to adults. At the 7 day retention test there was a trend toward significance for higher CR percentages at the CS-alone test in adults relative to periweanlings, though there were no age differences at reacquisition testing. When testing occurred 28 days after acquisition, however, periweanlings showed fewer CRs relative to adults during reacquisition despite low CR levels in both ages throughout the CS-alone test. Furthermore, periweanlings in the 28 day group required more trials at reacquisition than all other groups to exceed CR levels from their first acquisition session. These findings are consistent with rapid forgetting in the young commonly referred to as "infantile amnesia." The well-characterized eyeblink preparation may be useful for future studies investigating neural mechanisms responsible for rapid forgetting in developing animals.
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Conducta Animal/fisiología , Condicionamiento Palpebral/fisiología , Retención en Psicología/fisiología , Factores de Edad , Animales , Masculino , Ratas , Ratas Long-Evans , DesteteRESUMEN
Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In Experiment 1, post-natal day (P) 17 and 24 rats were trained to a criterion of 80% conditioned responses (CRs) using stimulation of the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS). Stimulation CS-alone extinction training commenced 24 h later, followed by reacquisition training after the fourth extinction session. Contrary to expected results, rats trained starting on P17 showed significantly fewer CRs to stimulation CS-alone presentations relative to P24s, including fewer CRs as early as the first block of extinction session 1. Furthermore, the P17 group was slower to reacquire following extinction. Experiment 2 was run to determine the extent to which the low CR percentage observed in P17s early in extinction reflected rapid forgetting versus rapid extinction. Twenty-four hours after reaching criterion, subjects were trained in a session split into 50 stimulation CS-unconditioned stimulus paired trials followed immediately by 50 stimulation CS-alone trials. With this "immediate" extinction protocol, CR percentages during the first block of stimulation CS-alone presentations were equivalent to terminal acquisition levels at both ages but extinction was more rapid in the P17 group. These findings indicate that forgetting is observed in P17 relative to P24 rats 24 h following acquisition. The forgetting in P17 rats has important implications for the neurobiological mechanisms of memory in the developing cerebellum.
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Condicionamiento Palpebral/fisiología , Extinción Psicológica/fisiología , Pedúnculo Cerebeloso Medio/crecimiento & desarrollo , Pedúnculo Cerebeloso Medio/fisiología , Animales , Estimulación Eléctrica , Electromiografía , Párpados/fisiología , Femenino , Neuroestimuladores Implantables , Masculino , Ratas Long-EvansRESUMEN
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 influenced by variables, such as the timing and dose of alcohol exposure. In a series of four experiments, we systematically examine how varying the timing and dose of alcohol exposure impact long delay and trace eyeblink conditioning in juvenile rats, tasks that both depend on a brainstem-cerebellar circuit but differ in that trace conditioning additionally recruits the hippocampus and prefrontal cortex. Using a "third-trimester-equivalent" alcohol exposure model, rats were exposed to a high binge dose of alcohol at one of two alcohol doses over postnatal days (PD) 4-9 or PD 7-9, windows of exposure thought to differentially target the cerebellum and hippocampus. Sham-intubated and untreated rats served as controls. As juveniles, rats from each treatment condition were trained in either a long delay or trace eyeblink conditioning task. Alcohol-exposed rats demonstrated general conditioning impairments compared to controls during long delay conditioning, with more robust impairments in rats exposed to the higher alcohol dose (5.25 g/kg/day) than those that received the lower dose (4.66 g/kg/day). Alcohol-exposed rats showed trace conditioning impairments compared to controls only when the high dose of alcohol was administered over PD 4-9 or PD 7-9. These findings indicate significant learning and memory impairments following neonatal alcohol exposure at both PD 4-9 and PD 7-9. The pattern of impairments across delay and trace conditioning suggest that alcohol disrupts processes that are common to both tasks. These findings are consistent with studies of delay and trace eyeblink conditioning in children with FASD. Future studies of the mechanisms underlying these deficits will further our understanding of brain injury and memory impairments resulting from developmental alcohol exposure.
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Animales Recién Nacidos/fisiología , Depresores del Sistema Nervioso Central/farmacología , Condicionamiento Palpebral/efectos de los fármacos , Etanol/farmacología , Envejecimiento/fisiología , Animales , Consumo Excesivo de Bebidas Alcohólicas/psicología , Peso Corporal/fisiología , Depresores del Sistema Nervioso Central/administración & dosificación , Depresores del Sistema Nervioso Central/sangre , Cerebelo/efectos de los fármacos , Interpretación Estadística de Datos , Relación Dosis-Respuesta a Droga , Electromiografía , Etanol/administración & dosificación , Etanol/sangre , Femenino , Trastornos del Espectro Alcohólico Fetal/psicología , Hipocampo/efectos de los fármacos , Masculino , Embarazo , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Long-EvansRESUMEN
Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17-21 or PD 24-28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17-24 in rats [Stanton et al., (1992) Behavioral Neuroscience, 106(4):657-665], another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24-28 showed greater conditioning relative to littermates trained from PD 17-21. Both age groups displayed poor retention of eyeblink conditioning at retraining 1 month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory.
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Condicionamiento Clásico/fisiología , Condicionamiento Palpebral/fisiología , Animales , Animales Recién Nacidos , Femenino , Masculino , ConejosRESUMEN
The context preexposure facilitation effect (CPFE) is an elaboration of contextual fear conditioning and refers to enhanced contextual conditioning resulting from preexposure to the context prior to a separate, brief context-shock episode. A version of the CPFE developed by Rudy and colleagues in rats has demonstrated greater sensitivity to pre-training hippocampal insult relative to standard contextual fear conditioning preparations. Our aim was to adapt the Rudy CPFE procedures to mice. In Experiment 1 we compared performance of young adult male C57BL6/J mice on two versions of the CPFE. One version - not previously used in mice - adapted methods established by Rudy and colleagues, and the other CPFE task replicated procedures previously established in this mouse strain by Gould and colleagues. In Experiment 2 we compared the effects of pre-training intraperitoneal administration of moderate levels of scopolamine or methylscopolamine on contextual conditioning between mice trained using the Rudy CPFE method and a separate group trained using standard contextual fear procedures. Scopolamine is a muscarinic cholinergic receptor antagonist that impairs hippocampal function. Robust freezing to the conditioning context was observed in mice trained using the Rudy CPFE method (Experiment 1), and greater scopolamine-induced impairments in contextual freezing were observed using this CPFE method relative to mice trained using standard contextual fear procedures (Experiment 2). These findings support use of the Rudy CPFE task as a behavioral assay for hippocampal function in mice.
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Antagonistas Colinérgicos/administración & dosificación , Condicionamiento Clásico/efectos de los fármacos , Miedo/efectos de los fármacos , Escopolamina/administración & dosificación , Análisis de Varianza , Animales , Condicionamiento Clásico/fisiología , Relación Dosis-Respuesta a Droga , Electrochoque , Reacción Cataléptica de Congelación , Masculino , Ratones , Ratones Endogámicos C57BL , N-Metilescopolamina/administración & dosificación , Refuerzo en Psicología , Grabación en VideoRESUMEN
Nicotinic acetylcholine receptors (nAChRs) are essentially involved in learning and memory. A neurobiologically and behaviorally well-characterized measure of learning and memory, eyeblink classical conditioning, is sensitive to disruptions in acetylcholine neurotransmission. The two most common forms of eyeblink classical conditioning - the delay and trace paradigms - differentially engage forebrain areas densely-populated with nAChRs. The present study used genetically modified mice to investigate the effects of selective nAChR subunit deletion on delay and trace eyeblink classical conditioning. α7 and ß2 nAChR subunit knockout (KO) mice and their wild-type littermates were trained for 10 daily sessions in a 500-ms delay or 500-ms trace eyeblink conditioning task, matched for the interstimulus interval between conditioned stimulus and unconditioned stimulus onset. Impairments in conditioned responding were found in α7 KO mice trained in trace - but not delay - eyeblink conditioning. Relative to littermate controls, ß2 KO mice were unimpaired in the trace task but displayed higher levels of conditioned responding in delay eyeblink conditioning. Elevated conditioned response levels in delay-conditioned ß2 KOs corresponded to elevated levels of alpha responding in this group. These findings suggest that α7 nAChRs play a role in normal acquisition of 500 ms trace eyeblink classical conditioning in mice. The prominent distribution of α7 nAChRs in the hippocampus and other forebrain regions may account for these genotype-specific acquisition effects in this hippocampus-dependent trace paradigm.
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Young adult Purkinje cell degeneration (pcd) mutant mice, with complete loss of cerebellar cortical Purkinje cells, are impaired in delay eyeblink classical conditioning. In the delay paradigm, the conditioned stimulus (CS) overlaps and coterminates with the unconditioned stimulus (US), and the cerebellar cortex supports normal acquisition. The ability of pcd mutant mice to acquire trace eyeblink conditioning in which the CS and US do not overlap has not been explored. Recent evidence suggests that cerebellar cortex may not be necessary for trace eyeblink classical conditioning. Using a 500 ms trace paradigm for which forebrain structures are essential in mice, we assessed the performance of homozygous male pcd mutant mice and their littermates in acquisition and extinction. In contrast to results with delay conditioning, acquisition of trace conditioning was unimpaired in pcd mutant mice. Extinction to the CS alone did not differ between pcd and littermate control mice, and timing of the conditioned response was not altered by the absence of Purkinje cells during acquisition or extinction. The ability of pcd mutant mice to acquire and extinguish trace eyeblink conditioning at levels comparable to controls suggests that the cerebellar cortex is not a critical component of the neural circuitry underlying trace conditioning. Results indicate that the essential neural circuitry for trace eyeblink conditioning involves connectivity that bypasses cerebellar cortex.
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Parpadeo/fisiología , Condicionamiento Clásico , Degeneración Nerviosa/patología , Células de Purkinje/patología , Animales , Cerebelo/patología , Electromiografía , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Degeneración Nerviosa/genéticaRESUMEN
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 found impairments in interstimulus interval (ISI) discrimination--a complex task variant of EBC--in adult rats following postnatal day (PD) 4-9 alcohol exposure at doses of 3, 4, and 5 g/kg/day. Because robust developmental differences in conditioned response (CR) generation and CR latency measures are present between untreated juveniles and adults in this task, we sought to extend alcohol findings to juvenile rats (PD30). Five neonatal treatment groups were used: (1) undisturbed controls, (2) sham intubation controls, (3) 3 g/kg/day of alcohol (blood alcohol concentration {BAC}=139.9 mg/dl), (4) 4 g/kg/day of alcohol (BAC=237.3 mg/dl), or (5) 5 g/kg/day of alcohol (BAC=301.8 mg/dl). Intubations occurred over PD4-9. ISI discrimination training in juveniles (PD30-33) revealed dose-dependent CR deficits in all three alcohol-exposed groups relative to controls. Contrary to expected outcomes, CR latency measures were not significantly affected as a function of neonatal treatment. Comparison of these findings with our recent study in adults suggests that alcohol-induced impairments in ISI discrimination EBC may be greater in adults relative to juveniles. The present findings provide further evidence that ISI discrimination may provide greater sensitivity to functional deficits resulting from moderate levels of neonatal alcohol exposure relative to single-cue EBC paradigms.
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Consumo de Bebidas Alcohólicas , Condicionamiento Palpebral/fisiología , Etanol/administración & dosificación , Adaptación Biológica , Análisis de Varianza , Animales , Animales Recién Nacidos , Parpadeo , Discriminación en Psicología , Electromiografía , Femenino , Masculino , Modelos Animales , Ratas , Ratas Long-Evans , Tiempo de ReacciónRESUMEN
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 rats show normal responses to conditioned and unconditioned stimuli, but they show marked differences from comparison groups in acquisition, magnitude, and timing of the conditioned response (CR). This study examined VPA-induced eyeblink CR timing differences by training rats on an interstimulus interval (ISI) discrimination task, in which two distinct conditioned stimuli (CS; tone and light) are paired with the same unconditioned stimulus (US; periocular shock) at two distinct CS-US intervals. Previous findings suggest that this task would produce abnormally large and prematurely timed CRs for VPA-exposed rats relative to controls. Adult male Long-Evans rats that were exposed to either VPA or saline on GD 12.5 were trained on an ISI discrimination task [Brown KL, Pagani JH, Stanton ME. The ontogeny of interstimulus interval (ISI) discrimination of the conditioned eyeblink response in rats. Behav Neurosci 2006;120: 1057-70.]. In support of earlier findings, we observed early acquisition and enhanced magnitude of the CR in VPA rats compared with controls on long CS trials. VPA rats also showed prematurely timed CRs to long- CS trials, but not to short- CS trials. The ISI discrimination procedure used in the current study reveals differential timed responses in this animal model of autism not previously seen.
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Trastorno Autístico/psicología , Condicionamiento Palpebral/fisiología , Animales , Trastorno Autístico/inducido químicamente , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Interpretación Estadística de Datos , Discriminación en Psicología/fisiología , Electromiografía , Femenino , Antagonistas del GABA/toxicidad , Crecimiento/efectos de los fármacos , Crecimiento/fisiología , Estimulación Luminosa , Desempeño Psicomotor/fisiología , Ratas , Ratas Long-Evans , Ácido Valproico/toxicidadRESUMEN
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.
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Percepción Auditiva , Condicionamiento Palpebral , Aprendizaje Discriminativo , Percepción del Tiempo , Transferencia de Experiencia en Psicología , Percepción Visual , Estimulación Acústica , Factores de Edad , Animales , Animales Recién Nacidos , Electrochoque , Femenino , Masculino , Estimulación Luminosa , Ratas , Ratas Long-Evans , Tiempo de Reacción , IncertidumbreRESUMEN
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 identify deficits in EBC using doses lower than those that have been reported previously following alcohol exposure limited to PD4-9. Complex conditioned response (CR) timing tasks utilizing 2 interstimulus intervals (ISIs) were used to test the hypothesis that 3 g/kg/day of alcohol would produce early onset and early peaked CRs, whereas 4 and 5 g/kg/day would impair CR acquisition. METHODS: Five neonatal treatment groups were used: (1) undisturbed controls, (2) sham intubation controls, (3) 3 g/kg/day of alcohol, (4) 4 g/kg/day of alcohol, or (5) 5 g/kg/day of alcohol. Intubations occurred over PD4-9. In adulthood, rats were trained using ISI discrimination (Experiment 1) or temporal uncertainty (Experiment 2) EBC tasks. In ISI discrimination, 2 distinct conditioned stimuli (CSs; tone and light) are reinforced with a periocular shock unconditioned stimulus (US) at 2 different CS-US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both CS-US intervals. RESULTS: Alcohol-exposed subjects were impaired in CR acquisition in a task- and dose-dependent fashion. CR deficits were most salient in the peak amplitude measure and occurred in both tasks following alcohol exposure at 4 and 5 g/kg/day. Alcohol at a dosage of 3 g/kg/day impaired CR acquisition only in ISI discrimination. All alcohol doses failed to produce short latency CRs in either task. Alcohol-exposed subjects displayed later-onset and later-peaked CRs to the long-ISI CS in ISI discrimination relative to controls. CONCLUSIONS: ISI discrimination training may be ideal to identify CR deficits resulting from neonatal exposure to moderate alcohol doses. Applications of this EBC task to humans may enable reliable early identification and diagnosis of individuals with fetal alcohol spectrum disorders.
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Intoxicación Alcohólica/fisiopatología , Cerebelo/fisiopatología , Condicionamiento Clásico/fisiología , Condicionamiento Palpebral/fisiología , Modelos Animales de Enfermedad , Trastornos del Espectro Alcohólico Fetal/fisiopatología , Percepción del Tiempo/fisiología , Animales , Animales Recién Nacidos , Aprendizaje Discriminativo/fisiología , Relación Dosis-Respuesta a Droga , Electromiografía , Etanol/sangre , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Ratas , Ratas Long-EvansRESUMEN
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 acute alcohol intubations across different developmental periods (postnatal day [PND] 4-9 or PND7-9) and tested them from PND26-31 on discriminative classical eyeblink conditioning and reversal. A high dose of alcohol (5 g/kg/day) dramatically impaired conditioning relative to controls when exposure occurred over PND4-9, but produced mild or no impairments when delivered over PND7-9. These findings support previous claims that developmental exposure period plays a critical role in determining the deleterious effects of alcohol on the developing brain. A lower dose of alcohol (4 g/kg/day) delivered from PND4-9--lower than has previously been shown to affect single-cue eyeblink conditioning--also produced deficits on the discrimination task, suggesting that discrimination learning and acquisition of responding to CS+ during reversal may be especially sensitive behavioral indicators of alcohol-induced brain damage in this rat model.
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Intoxicación Alcohólica/psicología , Condicionamiento Palpebral/efectos de los fármacos , Aprendizaje Discriminativo/efectos de los fármacos , Etanol/toxicidad , Aprendizaje Inverso/efectos de los fármacos , Animales , Animales Recién Nacidos , Daño Encefálico Crónico/psicología , Tronco Encefálico/efectos de los fármacos , Cerebelo/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas Long-Evans , DesteteRESUMEN
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 in reversal of instrumental discrimination learning . Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex. In order to explore behavioral parallels of the VPA rodent model with human autism, the present study exposed pregnant Long-Evans rats to 600 mg/kg VPA on GD12 and tested their offspring from Postnatal Day (PND26-31) on discriminative eyeblink conditioning and reversal. VPA rats showed faster eyeblink conditioning, consistent with studies in autistic children . This suggests that previously reported parallels between human autism and the VPA rodent model with respect to injury to brainstem-cerebellar circuitry are accompanied by behavioral parallels when a conditioning task engaging this circuitry is used. VPA rats also showed impaired reversal learning, but this likely reflected "carry-over" of enhanced conditioning during acquisition rather than a reversal learning deficit like that seen in human autism. Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder.
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Trastorno Autístico/fisiopatología , Condicionamiento Palpebral/fisiología , Aprendizaje Discriminativo/fisiología , Aprendizaje Inverso/fisiología , Análisis de Varianza , Animales , Trastorno Autístico/inducido químicamente , Femenino , Masculino , Exposición Materna , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Long-Evans , Teratógenos , Ácido ValproicoRESUMEN
The Ladolam hydrothermal system, on Lihir Island, Papua New Guinea, hosts one of the youngest and largest gold deposits in the world. Several deep (more than 1 kilometer) geothermal wells were drilled beneath the ore bodies to extract water at >275 degrees C and to facilitate open-pit mining. Using a titanium down-hole sampler, we determined that the deep geothermal brine of magmatic origin contains approximately 15 parts per billion gold. At the current gold flux of 24 kilograms per year, this deposit could have formed within approximately 55,000 years. The combination of sustained metal flux and efficient metal precipitation led to the formation of a giant hydrothermal gold deposit in a short period.
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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 in the ISI discrimination group relative to a control group receiving the short CS without reinforcement. Experiment 2 showed that early CR peak latencies and enhanced CR amplitudes to the long CS in the ISI discrimination group were due to associative pairing of the short CS and unconditioned stimulus. Experiment 3 demonstrated ISI discrimination in adults that was improved relative to younger subjects, but with no enhancement of CR amplitude to the long CS in the ISI discrimination group. Cerebellar cortical maturation may influence the ontogeny of CR timing.
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Parpadeo , Condicionamiento Clásico , Aprendizaje Discriminativo , Percepción del Tiempo , Estimulación Acústica , Animales , Animales Recién Nacidos , Femenino , Masculino , Memoria a Corto Plazo , Estimulación Luminosa , Ratas , Ratas Long-Evans , Tiempo de Reacción , DesteteRESUMEN
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, 1993; N. Spear, G. Smith, R. Bryan, & W. Gordon, 1980). The present study sought to examine this effect in an appetitive T-maze task, as a function of different contextual manipulations. Rats of three ages, Postnatal Day (PND) 19, PND23, and PND30, were tested for their ability to acquire and reverse a position habit in a T-maze. Contextual changes were made between acquisition and reversal sessions and consisted of one of three manipulations: (a) texture; the texture of the maze floor was changed via the addition or subtraction of wire mesh; (b) maze; subjects were reversed in a different maze that was identical in construction to the training maze, but differed in spatial location; (c) texture and maze; subjects were shifted to the new maze, the floor of which differed in texture from the training maze but was otherwise identical in construction. Results showed that the texture-maze combination was an effective aid to reversal learning at all ages tested. The texture alone, however, was not effective at any age. The maze alone also was an effective cue for reversal, but proved to have the greatest effect for PND30 subjects. During ontogeny, the contextual modulation of reversal learning is importantly influenced by the nature and the salience of the contextual cue.
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Aprendizaje Discriminativo/fisiología , Aprendizaje Inverso/fisiología , Percepción Espacial/fisiología , Factores de Edad , Análisis de Varianza , Animales , Señales (Psicología) , Femenino , Masculino , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Long-Evans , Tacto/fisiologíaRESUMEN
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, conditional discrimination was evident on Postnatal Day (PND) 30 when mesh+maze or maze-alone were the conditional cues, but not when mesh-alone was the cue. Experiment 2 confirmed that mesh-alone was sufficiently salient to support learning of a simple (nonconditional) discrimination. Its failure to serve as a conditional cue in Experiment 1 does not reflect its general ineffectiveness as a stimulus. Experiment 3 confirmed that the learning shown in Experiment 1 was indeed conditional in nature by comparing performance on conditional versus nonconditional versions of the task. Experiment 4 showed that PND19 and PND23 pups also were capable of performing the task when maze+mesh was the cue; however, the findings indicate that PND19 subjects do not use a conditional strategy to learn this task. The findings suggest postnatal ontogeny of conditional discrimination learning and underscore the importance of conditional cue salience, and of identifying task strategies, in developmental studies of conditional discrimination learning.