Faculty Research and Publications

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    Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex
    (Public Library of Science, 2014) Molina, Leonardo A.; Skelin, Ivan; Gruber, Aaron J.
    Antagonists of N-methyl-D-aspartate receptors (NMDAR) have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801) on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists.
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    Allostatic load and preterm birth
    (M D P I A G, 2015) Olson, David M.; Severson, Emily M.; Verstraeten, Barbara S. E.; Ng, Jane W. Y.; McCreary, J. Keiko; Metz, Gerlinde A. S.
    Preterm birth is a universal health problem that is one of the largest unmet medical needs contributing to the global burden of disease. Adding to its complexity is that there are no means to predict who is at risk when pregnancy begins or when women will actually deliver. Until these problems are addressed, there will be no interventions to reduce the risk because those who should be treated will not be known. Considerable evidence now exists that chronic life, generational or accumulated stress is a risk factor for preterm delivery in animal models and in women. This wear and tear on the body and mind is called allostatic load. This review explores the evidence that chronic stress contributes to preterm birth and other adverse pregnancy outcomes in animal and human studies. It explores how allostatic load can be used to, firstly, model stress and preterm birth in animal models and, secondly, how it can be used to develop a predictive model to assess relative risk among women in early pregnancy. Once care providers know who is in the highest risk group, interventions can be developed and applied to mitigate their risk.
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    Anatomical specializations for nocturnality in a critically endangered parrot, the Kakapo (Strigops habroptilus)
    (Public Library of Science, 2011) Corfield, Jeremy R.; Gsell, Anna C.; Brunton, Dianne; Heesy, Christopher P.; Hall, Margaret I.; Acosta, Monica L.; Iwaniuk, Andrew N.
    The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing is known about its’ visual system. Here, we provide a detailed morphological analysis of the orbits, brain, eye, and retina of the Kakapo and comparisons with other birds. Morphometric analyses revealed that the Kakapo’s orbits are significantly more convergent than other parrots, suggesting an increased binocular overlap in the visual field. The Kakapo exhibits an eye shape that is consistent with other nocturnal birds, including owls and nightjars, but is also within the range of the diurnal parrots. With respect to the brain, the Kakapo has a significantly smaller optic nerve and tectofugal visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium were significantly reduced in relative size compared to other parrots. There was no apparent reduction to the thalamofugal visual pathway. Finally, the retinal morphology of the Kakapo is similar to that of both diurnal and nocturnal birds, suggesting a retina that is specialised for a crepuscular niche. Overall, this suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a larger binocular field than other parrots. We conclude that the Kakapo possesses a visual system unlike that of either strictly nocturnal or diurnal birds and therefore does not adhere to the traditional view of the evolution of nocturnality in birds.
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    The anatomy of the bill tip of Kiwi and associated somatosensory regions of the brain: comparisons with shorebirds
    (Public Library of Science, 2013) Cunningham, Susan J.; Corfield, Jeremy R.; Iwaniuk, Andrew N.; Castro, Isabel; Alley, Maurice R.; Birkhead, Tim R.; Parsons, Stuart
    Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These ‘bill-tip organs’ allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), nonapterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation.
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    Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes
    (BioMed Central, 2014) Yao, Youli; Robinson, Alexandra M.; Zucchi, Fabiola C. R.; Robbins, Jerrah C.; Babenko, Olena M.; Kovalchuk, Olga; Kovalchuk, Igor; Olson, David M.; Metz, Gerlinde A. S.
    Abstract Background: Chronic stress is considered to be one of many causes of human preterm birth (PTB), but no direct evidence has yet been provided. Here we show in rats that stress across generations has downstream effects on endocrine, metabolic and behavioural manifestations of PTB possibly via microRNA (miRNA) regulation. Methods: Pregnant dams of the parental generation were exposed to stress from gestational days 12 to 18. Their pregnant daughters (F1) and grand-daughters (F2) either were stressed or remained as non-stressed controls. Gestational length, maternal gestational weight gain, blood glucose and plasma corticosterone levels, litter size and offspring weight gain from postnatal days 1 to 30 were recorded in each generation, including F3. Maternal behaviours were analysed for the first hour after completed parturition, and offspring sensorimotor development was recorded on postnatal day (P) 7. F0 through F2 maternal brain frontal cortex, uterus and placenta miRNA and gene expression patterns were used to identify stress-induced epigenetic regulatory pathways of maternal behaviour and pregnancy maintenance. Results: Progressively up to the F2 generation, stress gradually reduced gestational length, maternal weight gain and behavioural activity, and increased blood glucose levels. Reduced offspring growth and delayed behavioural development in the stress cohort was recognizable as early as P7, with the greatest effect in the F3 offspring of transgenerationally stressed mothers. Furthermore, stress altered miRNA expression patterns in the brain and uterus of F2 mothers, including the miR-200 family, which regulates pathways related to brain plasticity and parturition, respectively. Main miR-200 family target genes in the uterus, Stat5b, Zeb1 and Zeb2, were downregulated by multigenerational stress in the F1 generation. Zeb2 was also reduced in the stressed F2 generation, suggesting a causal mechanism for disturbed pregnancy maintenance. Additionally, stress increased placental miR-181a, a marker of human PTB. Conclusions: The findings indicate that a family history of stress may program central and peripheral pathways regulating gestational length and maternal and newborn health outcomes in the maternal lineage. This new paradigm may model the origin of many human PTB causes.
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    Arm and hand movement: current knowledge and future perspective
    (Frontiers Media, 2015) Morris, Renee; Whishaw, Ian Q.
    [No abstract available]
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    Articulation speaks to executive function: an investigation in 4- to 6-year olds
    (Frontiers Media, 2018) Netelenbos, Nicole; Gibb, Robbin L.; Li, Fangfang; Gonzalez, Claudia L. R.
    Executive function (EF) and language learning play a prominent role in early childhood development. Empirical research continues to point to a concurrent relation between these two faculties. What has been given little attention, however, is the association between EF and speech articulation abilities in children. This study investigated this relation in children aged 4–6 years. Significant correlations indicated that children with better EF [via parental report of the Behavior Rating Inventory of Executive Function (BRIEF)inventory] exhibited stronger speech sound production abilities in the articulation of the “s” and “sh” sounds. Furthermore, regression analyses revealed that the Global Executive Composite (GEC) of EF as measured by the BRIEF, served as a predictor for speech sound proficiency and that speech sound proficiency served as a predictor for the GEC. Together, these results demonstrate the imbricated nature of EF and speech sound production while bearing theoretical and practical implications. From a theoretical standpoint, the close link between EF and speech articulation may indicate a common ontogenetic pathway. From a practical perspective, the results suggest that children with speech difficulties could be at higher risk for EF deficits.
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    Avian cerebellar floccular fossa size is not a proxy for flying ability in birds
    (Public Library of Science, 2013) Walsh, Stig A.; Iwaniuk, Andrew N.; Knoll, Monja A.; Bourdon, Estelle; Barrett, Paul M.; Milner, Angela C.; Nudds, Robert L.; Abel, Richard L.; Sterpaio, Patricia Dello
    Extinct animal behavior has often been inferred from qualitative assessments of relative brain region size in fossil endocranial casts. For instance, flight capability in pterosaurs and early birds has been inferred from the relative size of the cerebellar flocculus, which in life protrudes from the lateral surface of the cerebellum. A primary role of the flocculus is to integrate sensory information about head rotation and translation to stabilize visual gaze via the vestibulo-occular reflex (VOR). Because gaze stabilization is a critical aspect of flight, some authors have suggested that the flocculus is enlarged in flying species. Whether this can be further extended to a floccular expansion in highly maneuverable flying species or floccular reduction in flightless species is unknown. Here, we used micro computed-tomography to reconstruct ‘‘virtual’’ endocranial casts of 60 extant bird species, to extract the same level of anatomical information offered by fossils. Volumes of the floccular fossa and entire brain cavity were measured and these values correlated with four indices of flying behavior. Although a weak positive relationship was found between floccular fossa size and brachial index, no significant relationship was found between floccular fossa size and any other flight mode classification. These findings could be the result of the bony endocranium inaccurately reflecting the size of the neural flocculus, but might also reflect the importance of the flocculus for all modes of locomotion in birds. We therefore conclude that the relative size of the flocculus of endocranial casts is an unreliable predictor of locomotor behavior in extinct birds, and probably also pterosaurs and non-avian dinosaurs.
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    Barriers to developing a valid rodent model of Alzheimer's disease: from behavioral analysis to etiological mechanisms
    (Frontiers Media, 2015) Gidyk, Darryl C.; Deibel, Scott H.; Hong, Nancy S.; McDonald, Robert J.
    Sporadic Alzheimer’s disease (AD) is the most prevalent form of age-related dementia. As such, great effort has been put forth to investigate the etiology, progression, and underlying mechanisms of the disease. Countless studies have been conducted, however, the details of this disease remain largely unknown. Rodent models provide opportunities to investigate certain aspects of AD that cannot be studied in humans. These animal models vary from study to study and have provided some insight, but no real advancements in the prevention or treatment of the disease. In this Hypothesis and Theory paper, we discuss what we perceive as barriers to impactful discovery in rodent AD research and we offer potential solutions for moving forward. Although no single model of AD is capable of providing the solution to the growing epidemic of the disease, we encourage a comprehensive approach that acknowledges the complex etiology of AD with the goal of enhancing the bidirectional translatability from bench to bedside and vice versa.
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    A Bayesian computational basis for auditory selective attention using head rotation and the interaural time-difference cue
    (Public Library of Science, 2017) Hambrook, Dillon A.; Ilievski, Marko; Mosadeghzad, Mohamad; Tata, Matthew S.
    The process of resolving mixtures of several sounds into their separate individual streams is known as auditory scene analysis and it remains a challenging task for computational systems. It is well-known that animals use binaural differences in arrival time and intensity at the two ears to find the arrival angle of sounds in the azimuthal plane, and this localization function has sometimes been considered sufficient to enable the un-mixing of complex scenes. However, the ability of such systems to resolve distinct sound sources in both space and frequency remains limited. The neural computations for detecting interaural time difference (ITD) have been well studied and have served as the inspiration for computational auditory scene analysis systems, however a crucial limitation of ITD models is that they produce ambiguous or “phantom” images in the scene. This has been thought to limit their usefulness at frequencies above about 1khz in humans. We present a simple Bayesian model and an implementation on a robot that uses ITD information recursively. The model makes use of head rotations to show that ITD information is sufficient to unambiguously resolve sound sources in both space and frequency. Contrary to commonly held assumptions about sound localization, we show that the ITD cue used with high-frequency sound can provide accurate and unambiguous localization and resolution of competing sounds. Our findings suggest that an “active hearing” approach could be useful in robotic systems that operate in natural, noisy settings. We also suggest that neurophysiological models of sound localization in animals could benefit from revision to include the influence of top-down memory and sensorimotor integration across head rotations.
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    Behavior systems approach to object play: stone handling repertoire as a measure of propensity for complex foraging and percussive tool use in the genus Macaca
    (SciKnow Publications, 2017) Pelletier, Amanda N.; Kaufmann, Tatjana; Mohak, Sidhesh; Milan, Riane; Nahallage, Charmalie A. D.; Huffman, Michael A.; Gunst, Noëlle; Rompis, Aida; Wandia, I Nengah; Arta Purta, I Gusti A.; Pellis, Sergio M.; Leca, Jean-Baptiste
    Stone handling (SH), has been identified in four closely related primate species of the Macaca genus. We provide the first ethogram of SH in long-tailed macaques (Macaca fascicularis), a primate species known to use stones for extractive foraging. A total of 62.7 hrs of video recorded data were scored from a population of Balinese long-tailed macaques living in Ubud, Bali, Indonesia, and a total of 36 stone handling patterns were identified. Behavior discovery curves were generated and showed that the minimum threshold of completeness was exceeded for the SH repertoire in this group. A “foraging substitute” hypothesis for the expression of SH was proposed, suggesting that SH consists of performing foraging-like actions on non-edible objects. We used a “behavior systems” framework to test this prediction, finding that all 36 stone handling patterns could be reliably categorized in a foraging behavior system, supporting the hypothesis that stone handling can be considered pseudo-foraging behavior. Our “behavior systems” approach will serve as a foundation for the future testing of the motivational basis of stone handling. Additionally, a comparison of 39 stone handling patterns performed by three macaque species (M. fascicularis, M. fuscata and M. mulatta) showed overlapping behavioral propensities to manipulate stones; however, the differences suggest that long-tailed macaques might be more prone to use stones as percussive tools in a foraging context. This work could offer insights into the development and evolution of complex activities such as percussive stone tool use in early humans.
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    Coevolution of relative brain size and life expectancy in parrots
    (The Royal Society Publishing, 2022) Smeele, Simeon Q.; Conde, Dalia A.; Baudisch, Annette; Bruslund, Simon; Iwaniuk, Andrew N.; Staerk, Johanna; Wright, Timothy F.; Young, Anna M.; McElreath, Mary Brooke; Aplin, Lucy
    Previous studies have demonstrated a correlation between longevity and brain size in a variety of taxa. Little research has been devoted to understanding this link in parrots; yet parrots are well-known for both their exceptionally long lives and cognitive complexity. We employed a large-scale comparative analysis that investigated the influence of brain size and life-history variables on longevity in parrots. Specifically, we addressed two hypotheses for evolutionary drivers of longevity: the cognitive buffer hypothesis, which proposes that increased cognitive abilities enable longer lifespans, and the expensive brain hypothesis, which holds that increases in lifespan are caused by prolonged developmental time of, and increased parental investment in, large-brained offspring. We estimated life expectancy from detailed zoo records for 133 818 individuals across 244 parrot species. Using a principled Bayesian approach that addresses data uncertainty and imputation of missing values, we found a consistent correlation between relative brain size and life expectancy in parrots. This correlation was best explained by a direct effect of relative brain size. Notably, we found no effects of developmental time, clutch size or age at first reproduction. Our results suggest that selection for enhanced cognitive abilities in parrots has in turn promoted longer lifespans.
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    Comparative analysis of the temporal impacts of corticosterone and simulated production stressors on the metabolome of broiler chickens
    (MDPI, 2023) Brown, Catherine L. J.; Zaytsoff, Sarah J. M.; Iwaniuk, Andrew N.; Metz, Gerlinde A. S.; Montina, Tony; Inglis, G. Douglas
    The impact of physiological stress on the metabolome of breast muscle, liver, kidney, and hippocampus was investigated in Ross 308 broiler chicks. Simulated on-farm stressors were compared to a corticosterone model of physiological stress. The three different stressors investigated were: (i) corticosterone at a dose of 15 mg/kg of feed; (ii) heat treatment of 36 °C and 40% RH for 8 h per day; and (iii) isolation for 1 h per day. Liver, kidney, breast muscle, and hippocampus samples were taken after 2, 4, 6, and 8 days of stress treatment, and subjected to untargeted 1H-nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis to provide insights on how stress can modulate metabolite profiles and biomarker discovery. Many of the metabolites that were significantly altered in tissues were amino acids, with glycine and alanine showing promise as candidate biomarkers of stress. Corticosterone was shown to significantly alter alanine, aspartate, and glutamate metabolism in the liver, breast, and hippocampus, while isolation altered the same pathways, but only in the kidneys and hippocampus. Isolation also significantly altered the glycine, serine, and threonine metabolism pathway in the liver and breast, while the same pathway was significantly altered by heat in the liver, kidneys, and hippocampus. The study’s findings support corticosterone as a model of stress. Moreover, a number of potential metabolite biomarkers were identified in chicken tissues, which may allow producers to effectively monitor stress and to objectively develop and evaluate on-farm mitigations, including practices that reduce stress and enhance bird health.
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    Computational properties of the hippocampus increase the efficiency of goal-directed foraging through hierarchical reinforcement learning
    (Frontiers Media, 2016) Chalmers, Eric; Luczak, Artur; Gruber, Aaron J.
    The mammalian brain is thought to use a version of Model-based Reinforcement Learning (MBRL) to guide “goal-directed” behavior, wherein animals consider goals and make plans to acquire desired outcomes. However, conventional MBRL algorithms do not fully explain animals’ ability to rapidly adapt to environmental changes, or learn multiple complex tasks. They also require extensive computation, suggesting that goal-directed behavior is cognitively expensive. We propose here that key features of processing in the hippocampus support a flexible MBRL mechanism for spatial navigation that is computationally efficient and can adapt quickly to change. We investigate this idea by implementing a computational MBRL framework that incorporates features inspired by computational properties of the hippocampus: a hierarchical representation of space, “forward sweeps” through future spatial trajectories, and context-driven remapping of place cells. We find that a hierarchical abstraction of space greatly reduces the computational load (mental effort) required for adaptation to changing environmental conditions, and allows efficient scaling to large problems. It also allows abstract knowledge gained at high levels to guide adaptation to new obstacles. Moreover, a context-driven remapping mechanism allows learning and memory of multiple tasks. Simulating dorsal or ventral hippocampal lesions in our computational framework qualitatively reproduces behavioral deficits observed in rodents with analogous lesions. The framework may thus embody key features of how the brain organizes model-based RL to efficiently solve navigation and other difficult tasks.
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    Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior
    (Frontiers Media, 2012) Gruber, Aaron J.; McDonald, Robert J.
    Motivated behavior exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioral control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum (VS), amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioral responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching) in accordance with associated stimulus valence (negative, neutral, positive), but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum (DMS) and habitual control involving dorsolateral striatum (DLS). The hippocampus provides contextual specificityto the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the striatum to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision-makingmay better aligntheoretical predictions with behavioral and neural correlates in animals.
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    Correction: Dynamics of distraction: competition among auditory streams modulates gain and disrupts inter-trial phase coherence in the human electroencephalogram
    (Public Library of Science, 2013) Ponjavic-Conte, Karla D.; Hambrook, Dillon A.; Pavlovic, Sebastian; Tata, Matthew S.
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    Cortical connectivity maps reveal anatomically distinct areas in the parietal cortex of the rat
    (Frontiers Media, 2014) Wilber, Aaron A.; Clark, Benjamin J.; Demecha, Alexis J.; Mesina, Lilia; Vos, Jessica M.; McNaughton, Bruce L.
    A central feature of theories of spatial navigation involves the representation of spatial relationships between objects in complex environments. The parietal cortex has long been linked to the processing of spatial visual information and recent evidence from single unit recording in rodents suggests a role for this region in encoding egocentric and world-centered frames. The rat parietal cortex can be subdivided into four distinct rostral-caudal andmedial-lateral regions,which includesazonepreviously characterized as secondary visual cortex. At present, very little is known regarding the relative connectivity of these parietal subdivisions. Thus, we set out to map the connectivity of the entire anterior-posterior and medial-lateral span of this region. To do this we used anterograde and retrograde tracers in conjunction with open source neuronal segmentation and tracer detection tools to generate whole brain connectivity maps of parietal inputs and outputs. Our present results show that inputs to the parietal cortex varied significantly along the medial-lateral, but not the rostral-caudal axis. Specifically, retrosplenial connectivity is greater medially, but connectivity with visual cortex, though generally sparse, is more significantlaterally.Finally,basedonconnectiondensity,theconnectivitybetweenparietal cortex and hippocampus is indirect and likely achieved largely via dysgranular retrosplenial cortex. Thus, similar to primates, the parietal cortex of rats exhibits a difference in connectivity along the medial-lateral axis, which may represent functionally distinct areas.
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    Corticosterone response to gestational stress and postpartum memory function in mice
    (Public Library of Science, 2017) Jafari, Zahra; Mehla, Jogender; Afrashteh, Navvab; Kolb, Bryan; Mohajerani, Majid H.
    Maternal stress is a common adversity during pregnancy. Gestational corticosterone alternations are thought to contribute to the etiology of postpartum behavioral disturbances. However, the impact of stress during pregnancy, in particular noise exposure, on gestational corticosterone fluctuations and spatial cognition in postpartum mice has not been fully understood yet. We hypothesized that noise exposure during pregnancy negatively affects gestational corticosterone levels and postpartum memory function in the dams similar to the physical stressors. Pregnant C57BL/6 mice were randomly assigned to either one of two stress conditions or a control condition. The noise stress (NS) was induced by presenting a loud intermittent 3000 Hz frequency on gestational days (GDs) 12, 14, and 16 for 24 hours, whereas the physical stress (PS) consisted of restraint and exposure to an elevated platform on GDs 12–16. Plasma corticosterone level was collected on GDs 11 and 17, and Morris water task (MWT) was carried out 30 days after parturition. Compared to the control group, the level of corticosterone in the stressed groups was significantly increased on GD17 relative to GD11. Significantly longer swim time and lower swim speed were observed in both stressed groups relative to the control group. Probe time was significantly shorter in the NS group than the other groups. The delta corticosterone level was significantly correlated with the swim time as well as the probe time in the three groups. Given the results, the adverse effects of gestational noise exposure on the hypothalamic pituitary-adrenal (HPA) axis activation and postpartum spatial learning and memory function were as large as/ or a bit stronger than the physical stresses. The findings suggest the significance of conservation against loud noise exposure in daily living, as well as need to further notice to the different aspects of gestational stress in mothers’ behavior like offspring.
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    dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients
    (Macmillan Publishers, 2013) Manitt, C.; Eng, C.; Pokinko, M.; Ryan, R. T.; Torres-Berrio, A.; Lopez, J. P.; Yogendran, S. V.; Daubaras, M. J. J.; Grant, A.; Schmidt, E. R. E.; Tronche, F.; Krimpenfort, P.; Cooper, H. M.; Pasterkamp, R. J.; Kolb, Bryan; Turecki, G.; Wong, T. P.; Nestler, E. J.; Giros, B.; Flores, C.
    Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.
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    The development of juvenile-typical patterns of play fighting in juvenile rats does not depend on peer-peer play experience in the peri-weaning period
    (eScholarship Publishing, University of California, 2015) Himmler, Brett T.; Himmler, Stephanie M.; Stryjek, Rafal; Modlinska, Klaudia; Pisula, Wojciech; Pellis, Sergio M.
    Play fighting in rats involves attack and defense of the nape. To protect the nape, rats use a variety of defensive tactics, with different strains having specific preferences. Targeting of the nape is established before weaning and defense matures over the course of the week preceding and the week proceeding weaning. Thus, it is possible that experience from engaging in immature forms of play is needed to consolidate the nape as the playful target and for the development of the juvenile-typical pattern of defense. Two experiments were conducted to evaluate this possibility. For the first experiment, male rats were reared over the week post-weaning in either pairs or alone, and their play tested with unfamiliar partners when juveniles (31-34 days). For the second experiment, during the week preceding weaning, male and female rats were placed into one of three conditions: (1) with the mother and no peers, (2) with same-sex siblings but no mother, or (3) with both the mother and same-sex siblings. The subjects were tested in same-sex, samecondition pairs when juveniles (31-34 days). Rats from all conditions, in both experiments, attacked the nape during play fighting and developed the same juvenile-typical patterns of playful defense. This suggests that the experience of peer-peer play in the peri-weaning period is not necessary for the development of the attack and defense components of juvenile-typical play.