• Co-Occurrence of Sleep Oscillations in Hippocampus and Prefrontal Cortex in a Memory Consolidation Task

      Cowen, Stephen; Harper, Blaine; Cowen, Stephen; Nadel, Lynn; Fellous, Jean-Marc (The University of Arizona., 2017)
      The co-occurrence of hippocampal sharp-wave ripple oscillations (100-250 Hz) and cortical spindle oscillations (12-15 Hz) is thought to be a key mechanism for memory consolidation. The present study uses simultaneous recordings from dorsal hippocampal area CA1 and from the prelimbic area of the medial prefrontal cortex (mPFC) in adult male Brown Norway rats to test the hypothesis that learning-related increases in oscillation density enhance the cross-correlation between ripples and spindles. We first confirm that ripple and spindle density increase during sleep after learning in a spatial navigation task on an open field maze. Same-day recordings of learning and non-learning tasks show no significant enhancement of ripple-spindle cross-correlation during post-task sleep. The percentages of spindles with co-occurring ripples and of ripples occurring during or near spindles do not vary significantly with task. However, ripples appear to occur before, during, and after spindles at rates greater than chance. This suggests that the statistics of ripple and spindle co-occurrence may be fixed, with increased oscillation densities potentially enhancing single unit interactions between regions.
    • Development of Relational Memory in Middle Childhood: Evidence from Eye Movements

      Edgin, Jamie; Liu, Yating; Edgin, Jamie; Gomez, Rebecca; Nadel, Lynn (The University of Arizona., 2015)
      Relational memory refers to memory for arbitrary associations among components of experience, and is thought to be critically dependent on the hippocampus. Previous studies suggested that age-related differences in relational memory were consistent with a protracted developmental trajectory of hippocampus. Recently, eye tracking studies conducted in infants have concluded that eye movement detection could provide one indirect index of relational memory and hippocampal function in infants as young as 6 months. While the eye-based memory expression has been detected in adults on relational memory tasks, this effect has been less studied across development, and the few studies that have been conducted have suggested discontinuity in eye-movement behaviors across age. The purpose of the current study is to examine the development of relational memory in middle childhood (7-8 years of age) by utilizing a face-scene binding paradigm. Behavioral results revealed that adults showed higher identification accuracy than children when recalling matching faces based on scene cues. The eye movement data indicated that adults showed stronger and more rapid looking preference to matching face during correct test trials, and the proportion of viewing time towards matching face was significantly greater than children on incorrect trials (while performance was below chance in both age groups). Therefore, eye movements do index relational memory and correct responses but show rapid onset only in adults. We discuss these results in the context of the neural systems that may support eye movement behavior across the lifespan and conclude that more work is required to determine the nature and strength of these effects prior to adopting eye-movements as a continuous measure of relational memory across development.
    • The effects of early experience on cognitive functioning in the rat

      Nadel, Lynn; Wilson, Lynn Allison, 1953- (The University of Arizona., 1989)
      Forty-eight rat pups were handled and isolated from postnatal days 3 through 13 in order to determine whether this manipulation would alter the postnatal development of the hippocampus. Half of these animals were then reared in enriched environments from weaning until maturity to determine whether enrichment would ameliorate the expected deficits in learning ability. Beginning at 90 days of age, all animals were tested on a T-maze, rotating bar and both place and cued versions of a water maze task. The study failed to find gross deficits in learning as a result of the handling/isolation procedure, although emotional differences between groups was evident, as were sex differences. Apparently more questions have been raised than answered by this study, and possible directions for future research are discussed.
    • The effects of postnatal zinc deficiency on spatial learning in rats

      Nadel, Lynn; Warren, Stacey Gayle, 1962- (The University of Arizona., 1990)
      The effects of postnatal zinc deficiency on the development of the hippocampal formation was assessed using the Morris water tank task. Tests at days 28, 29, 88 and 89 revealed no differences between ad libitum zinc deficient animals and ad libitum controls. Subjects whose food intake was restricted but was zinc adequate were impaired on the hippocampal version of this task but not the control version. These results suggest that previous reports of hippocampal impairment secondary to zinc deficiency should be re-evaluated.
    • The effects of serotonergic disruption on the locomotor response induced by cocaine, phencyclidine, and a phencyclidine analog

      French, Edward D.; Nadel, Lynn; Simms, Debra Kay, 1959- (The University of Arizona., 1990)
      This study assessed the involvement of serotonergic systems in the locomotor-stimulating effects of cocaine, phencyclidine (PCP), and the PCP analog, N- (1-(2-benzo(b)thiophenyl)cyclohexyl) piperidine (BTCP). Central serotonin (5-HT) activity was disrupted in rats with para-chloroamphetamine (p-CA), or ritanserin pretreatment, and by lesioning of the medial raphe (MR) and dorsal raphe (DR) nuclei. P-CA potentiated cocaine- and PCP- but not BTCP-induced hyperactivity. Ritanserin enhanced PCP hyperlocomotion and attenuated caffeine hyperactivity, but failed to alter cocaine and BTCP hyperlocomotion. MR lesions, but not DR lesions, dramatically increased spontaneous activity and potentiated the hyperlocomotion of cocaine, BTCP, and caffeine but not of PCP. This differential sensitivity to 5-HT disruption may reflect the relative importance of 5-HT systems in mediating the dopamine-dependent actions of these drugs. These results are discussed in relation to the neurochemical bases of drug reinforcement and schizophrenia.
    • The electrophysiological characterization of phencyclidine analogs on ventral tegmental area dopamine neurons

      French, Edward D.; Nadel, Lynn; Lin, Jingyang, 1962- (The University of Arizona., 1990)
      This study was designed to characterize the effects of PCP and PCP derivatives on dopamine systems using electrophysiological and behavioral methods. TCP, a high affinity PCP/NMDA receptor ligand only increased A10 firing while BTCP, a high affinity DA reuptake ligand only decreased activity. PCP with similar affinity for the NMDA and reuptake sites, produced a dose dependent bimodal change in the activity of A10 neurons. Lesions of the nucleus accumbens or treatment with picrotoxin, a GABA antagonist attenuated the BTCP and high dose PCP inhibitory effects thus supporting the existence of a GABAergic accumbal-VTA feedback pathway. Furthermore, BTCP and PCP produced significant increases in locomotor activity which were attenuated by accumbens lesions. The present data provide an explanation for PCP's bimodal effects and possibly for its psychotomimetic properties as well as abuse liability which may reside with its blockade of dopamine reuptake in the mesolimbic system.
    • Implicit and explicit memory in individuals with Down syndrome

      Nadel, Lynn; Newman, Mary Catherine (The University of Arizona., 1992)
      A growing body of literature focuses on comparisons between developmental disabilities of diverse etiologies including Down syndrome (DS). Earlier research emphasized the limitations of this population, and frequently subjects with DS did not compare favorably with control groups. The current investigation examined the implicit and explicit memory skills of individuals with Down syndrome, other developmental disabilities, and MA-matched nonhandicapped children while controlling for confounding variables. In contrast to many previous studies, it was determined that under controlled conditions, free recall and recognition memory of children with DS are equivalent to that of NDS and NH groups. And performance on a pursuit rotor task was also comparable between groups. However, priming of subjects with DS was inferior to controls, a deficit similar to that previously identified in patients with Alzheimer's disease. In addition, the DS group was mildly impaired in both word fluency and attention.
    • Mechanisms of Word-Learning in Typical and Atypical Development

      Edgin, Jamie; Sakhon, Stella; Edgin, Jamie; Nadel, Lynn; Glisky, Elizabeth (The University of Arizona., 2016)
      The hippocampus plays a critical role in binding together information into an integrated memory, and memory for these arbitrary associations is important when learning new words. Recent studies have investigated a learning mechanism called fast mapping (FM), showing that rapid acquisition of novel arbitrary associations can be learned independent of the hippocampus. In the current study we examine word-learning across two conditions more and less likely to require information integration via the hippocampus in typically developing children and individuals with hippocampal dysfunction (e.g., Down syndrome). Individuals with Down syndrome (DS) manifest hippocampal dysfunction and display memory and learning difficulties, hence could potentially benefit from alternative learning strategies. The current study found no benefit of the FM condition in either group. Both groups performed similarly and above chance level across the two conditions and over a week's delay, but a delay by group interaction suggested that the typically developing children showed improvement across all conditions after 1 week whereas performance in DS stayed consistent. Given evidence for sleep deficits in DS we examined how sleep disturbance related to delayed word retention. Sleep efficiency did not appear to be driving maintenance in either group. Future studies investigating when an individual with DS sleeps after learning, could provide a better understanding of how sleep can influence the word learning process. Additionally, future studies in an older group of children can also provide information on when the hippocampus and sleep dependent learning may develop in childhood.
    • Perceptual Mnemonic Medial Temporal Lobe Function in Individuals with Down Syndrome

      Edgin, Jamie Ogline; Spanò, Goffredina; Nadel, Lynn; Peterson, Mary A. (The University of Arizona., 2012)
      Behavioral data in individuals with Down syndrome (DS) and mouse models of the syndrome suggest impaired object processing. In this study we examined the component processes that may contribute to object memory deficits. A neuropsychological test battery was administered to individuals with DS (n=28), including tests targeting perirhinal cortex (PRC) and prefrontal cortex (PFC) function, tests of perception (i.e., convexity based figure ground perception), and tests of memory (object recognition and object-in-place learning). To compare to individuals with DS, the same number of typically developing chronological age (CA, n=28) and mental age-matched (MA, n=28) controls were recruited. We observed object memory deficits in DS (p<0.001). In contrast, the DS group showed relatively intact use of convexity when making figure-ground judgments and spared PRC-dependent function, as compared to MA control. In addition, measures of PFC function seemed to be related to performance on object recognition tasks. These findings suggest that the inputs into the MTL from low and high level perceptual processing streams may be intact in DS. The object memory deficits we observed might reflect impaired PFC function.
    • A psychobiological exploration of mental rotation in three groups of children: Control, learning disabled, and Down syndrome

      Nadel, Lynn; Uecker, Anne Cantalupo, 1960- (The University of Arizona., 1991)
      The present study investigated anomalous hemispheric processing for language and its impact on spatial task performance. Mental rotation and dichotic listening tasks were administered to three groups of children: control (C), learning disabled (LD), and Down syndrome (DS). Significant differences were found in reaction time and accuracy measures in mental rotation. Although the DS group lacked a systematic reaction time function, all three groups produced similar accuracy functions: each group appeared to demonstrate difficulty at equivalent angular disorientations. Dichotic listening resulted in performance differences only when the DS group was compared to the C and LD groups: discrepant language processing was not demonstrated between the C and LD groups. Conclusions could not be reached regarding the impact of language lateralization on spatial task performance. Inconsistencies of neuropsychological measurements are discussed; the topic of mental rotation is explored in depth. Generalizations regarding performance outcomes are limited to a behavioral level.