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Sample records for adult neural plasticity

  1. Experience-dependent neural plasticity in the adult damaged brain

    PubMed Central

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by injury to the adult brain. When experience impacts these same neural circuits, it interacts with degenerative and regenerative cascades to shape neural reorganization and functional outcome. This is evident in the cortical plasticity resulting from compensatory reliance on the “good” forelimb in rats with unilateral sensorimotor cortical infarcts. Behavioral interventions (e.g., rehabilitative training) can drive functionally beneficial neural reorganization in the injured hemisphere. However, experience can have both behaviorally beneficial and detrimental effects. The interactions between experience-dependent and injury-induced neural plasticity are complex, time-dependent, and varied with age and other factors. A better understanding of these interactions is needed to understand how to optimize brain remodeling and functional outcome. Learning outcomes Readers will be able to describe (a) experience effects that are maladaptive for behavioral outcome after brain damage, (b) manipulations of experience that drive functionally beneficial neural plasticity, and (c) reasons why rehabilitative training effects can be expected to vary with age, training duration and timing. PMID:21620413

  2. Auditory Training: Evidence for Neural Plasticity in Older Adults

    PubMed Central

    Anderson, Samira; Kraus, Nina

    2014-01-01

    Improvements in digital amplification, cochlear implants, and other innovations have extended the potential for improving hearing function; yet, there remains a need for further hearing improvement in challenging listening situations, such as when trying to understand speech in noise or when listening to music. Here, we review evidence from animal and human models of plasticity in the brain’s ability to process speech and other meaningful stimuli. We considered studies targeting populations of younger through older adults, emphasizing studies that have employed randomized controlled designs and have made connections between neural and behavioral changes. Overall results indicate that the brain remains malleable through older adulthood, provided that treatment algorithms have been modified to allow for changes in learning with age. Improvements in speech-in-noise perception and cognition function accompany neural changes in auditory processing. The training-related improvements noted across studies support the need to consider auditory training strategies in the management of individuals who express concerns about hearing in difficult listening situations. Given evidence from studies engaging the brain’s reward centers, future research should consider how these centers can be naturally activated during training. PMID:25485037

  3. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  4. Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

    PubMed

    Fernández, Guillén; Weis, Susanne; Stoffel-Wagner, Birgit; Tendolkar, Indira; Reuber, Markus; Beyenburg, Stefan; Klaver, Peter; Fell, Jürgen; de Greiff, Armin; Ruhlmann, Jürgen; Reul, Jürgen; Elger, Christian E

    2003-05-01

    In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.

  5. Distinctive features of adult ocular dominance plasticity.

    PubMed

    Sato, Masaaki; Stryker, Michael P

    2008-10-08

    Sensory experience profoundly shapes neural circuitry of juvenile brain. Although the visual cortex of adult rodents retains a capacity for plasticity in response to monocular visual deprivation, the nature of this plasticity and the neural circuit changes that accompany it remain enigmatic. Here, we investigate differences between adult and juvenile ocular dominance plasticity using Fourier optical imaging of intrinsic signals in mouse visual cortex. This comparison reveals that adult plasticity takes longer than in the juvenile mouse, is of smaller magnitude, has a greater contribution from the increase in response to the open eye, and has less effect on the hemisphere ipsilateral to the deprived eye. Binocular deprivation also causes different changes in the adult. Adult plasticity is similar to juvenile plasticity in its dependence on signaling through NMDA receptors. We propose that adult ocular dominance plasticity arises from compensatory mechanisms that counterbalance the loss of afferent activity caused by visual deprivation.

  6. Adult myelination: wrapping up neuronal plasticity

    PubMed Central

    O’Rourke, Megan; Gasperini, Robert; Young, Kaylene M.

    2014-01-01

    In this review, we outline the major neural plasticity mechanisms that have been identified in the adult central nervous system (CNS), and offer a perspective on how they regulate CNS function. In particular we examine how myelin plasticity can operate alongside neurogenesis and synaptic plasticity to influence information processing and transfer in the mature CNS. PMID:25221576

  7. Odor Experiences during Preimaginal Stages Cause Behavioral and Neural Plasticity in Adult Honeybees

    PubMed Central

    Ramírez, Gabriela; Fagundez, Carol; Grosso, Juan P.; Argibay, Pablo; Arenas, Andrés; Farina, Walter M.

    2016-01-01

    In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3–5- and 17–19 day-old bees, in the regulation of their expression of synaptic-related genes and in the perception and morphology of their antennae. Three-five day old bees that experienced 1-hexanol (1-HEX) as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e., bees reared in colonies fed unscented food). Higher levels of proboscis extension response (PER) to 1-HEX in this group also extended to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins (NRXs) and neuroligins (Nlgs) expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects. PMID:27375445

  8. Odor Experiences during Preimaginal Stages Cause Behavioral and Neural Plasticity in Adult Honeybees.

    PubMed

    Ramírez, Gabriela; Fagundez, Carol; Grosso, Juan P; Argibay, Pablo; Arenas, Andrés; Farina, Walter M

    2016-01-01

    In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3-5- and 17-19 day-old bees, in the regulation of their expression of synaptic-related genes and in the perception and morphology of their antennae. Three-five day old bees that experienced 1-hexanol (1-HEX) as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e., bees reared in colonies fed unscented food). Higher levels of proboscis extension response (PER) to 1-HEX in this group also extended to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins (NRXs) and neuroligins (Nlgs) expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects.

  9. Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats

    PubMed Central

    McCall, Nora; Mahadevia, Darshini; Corriveau, Jennifer A.; Glenn, Melissa

    2016-01-01

    The present study explored the effects of supplementing male rats with either choline, omega-3 fatty acids, or phytoestrogens, from weaning into early adulthood, on emotionality and hippocampal plasticity. Because of the neuroprotective properties of these nutrients, we hypothesized that they would positively affect both behavior and hippocampal function when compared to non-supplemented control rats. To test this hypothesis, male Sprague Dawley rats were assigned to one of four nutrient conditions after weaning: 1) control (normal rat chow); 2) choline (supplemented in drinking water); 3) omega 3 fatty acids (daily oral supplements); or 4) phytoestrogens (supplemented in chow). After 4 weeks on their respective diets, a subset of rats began 3 weeks of behavioral testing, while the remaining behaviorally naïve rats were sacrificed after 6 weeks on the diets to assess numbers of adult-born hippocampal neurons using the immature neuron marker, doublecortin. The results revealed that choline supplementation affected emotional functioning; compared to rats in other diet conditions, rats in this group were less anxious in an open field and after exposure to predator odor and showed less behavioral despair after forced swimming. Similar behavioral findings were evident following supplementation with omega-3 fatty acids and phytoestrogens supplementation, though not on all tests and not to the same magnitude. Histological findings followed a pattern consistent with the behavioral findings: choline supplementation, followed by omega-3 fatty acid supplementation, but not phytoestrogen supplementation, significantly increased the numbers of new-born hippocampal neurons. Choline and omega −3 fatty acids have similar biological functions—affecting cell membranes, growth factor levels, and epigenetically altering gene transcription. Thus, the present findings suggest that targeting nutrients with these effects may be a viable strategy to combat adult psychopathologies

  10. High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids

    PubMed Central

    Peirouvi, T.; Yekani, F.; Azarnia, M.; Massumi, M.

    2015-01-01

    Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic cerebrospinal fluid (E-CSF) including E13.5, E17-CSF and the adult cerebrospinal fluid (A-CSF), all extracted from rats. CSF samples were selected based on their effects on cell behavioral parameters. Primary cell culture was performed in the presence of either normal or high levels of KCL in a culture medium. High levels of KCL cause cell depolarization, and thus the activation of quiescent NSCs. Results from immunocytochemistry (ICC) and semi-quantitative RT-PCR (sRT-PCR) techniques showed that in E-CSF-treated groups, neuronal differentiation increased (E17>E13.5). In contrast, A-CSF decreased and increased neuronal and astroglial differentiations, respectively. Cell survivability and/or proliferation (S/P), evaluated by an MTT assay, increased by E13.5 CSF, but decreased by both E17 CSF and A-CSF. Based on the results, it is finally concluded that adult rat hippocampal proliferative cells are not restricted progenitors but rather show high plasticity in neuronal/astroglial differentiation according to the effects of CSF samples. In addition, using high concentrations of KCL in the primary cell culture led to an increase in the number of NSCs, which in turn resulted in the increase in neuronal or astroglial differentiations after CSF treatment. PMID:27175157

  11. Neural prostheses and brain plasticity

    NASA Astrophysics Data System (ADS)

    Fallon, James B.; Irvine, Dexter R. F.; Shepherd, Robert K.

    2009-12-01

    The success of modern neural prostheses is dependent on a complex interplay between the devices' hardware and software and the dynamic environment in which the devices operate: the patient's body or 'wetware'. Over 120 000 severe/profoundly deaf individuals presently receive information enabling auditory awareness and speech perception from cochlear implants. The cochlear implant therefore provides a useful case study for a review of the complex interactions between hardware, software and wetware, and of the important role of the dynamic nature of wetware. In the case of neural prostheses, the most critical component of that wetware is the central nervous system. This paper will examine the evidence of changes in the central auditory system that contribute to changes in performance with a cochlear implant, and discuss how these changes relate to electrophysiological and functional imaging studies in humans. The relationship between the human data and evidence from animals of the remarkable capacity for plastic change of the central auditory system, even into adulthood, will then be examined. Finally, we will discuss the role of brain plasticity in neural prostheses in general.

  12. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  13. Neural Prostheses and Brain Plasticity

    PubMed Central

    Fallon, James B.; Irvine, Dexter R. F.; Shepherd, Robert K.

    2010-01-01

    The success of modern neural prostheses is dependent on a complex interplay between the devices’ hardware and software and the dynamic environment in which the devices operate: the patient’s body or ‘wetware’. Over 110,000 severe/profoundly deaf individuals presently receive information enabling auditory awareness and speech perception from cochlear implants. The cochlear implant therefore provides a useful case study for a review of the complex interactions between hardware, software and wetware, and of the important role of the dynamic nature of wetware. This review will examine the evidence of changes in the wetware contributing to changes in speech perception and discuss how these changes relate to electrophysiological and functional imaging studies in humans. The relationship between the human data and evidence from animals of the remarkable capacity for plastic change of the central auditory system, even into adulthood, will then be examined. Finally, we will discuss the role of brain plasticity in neural prostheses in general. PMID:19850976

  14. Neural plasticity after spinal cord injury☆

    PubMed Central

    Liu, Jian; Yang, Xiaoyu; Jiang, Lianying; Wang, Chunxin; Yang, Maoguang

    2012-01-01

    Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have been studied, the mechanism and treatment to effectively improve neural plasticity changes remain controversial. The present study reviewed studies regarding plasticity of the central nervous system and methods for promoting plasticity to improve repair of injured central nerves. The results showed that synaptic reorganization, axonal sprouting, and neurogenesis are critical factors for neural circuit reconstruction. Directed functional exercise, neurotrophic factor and transplantation of nerve-derived and non-nerve-derived tissues and cells can effectively ameliorate functional disturbances caused by spinal cord injury and improve quality of life for patients. PMID:25774179

  15. Neural Plasticity: For Good and Bad

    NASA Astrophysics Data System (ADS)

    Møller, A. R.

    The brain's ability to change its organization and function is necessary for normal development of the nervous system and it makes it possible to adapt to changing demands but it can also cause disorders when going awry. This property, known as neural plasticity, is only evident when induced, very much like genes. Plastic changes may be programmed and providing a ``midcourse correction" during childhood development. If that is not executed in the normal way severe developmental disorders such as autism may results. Normal development of functions and anatomical organization of the brain and the spinal cord depend on appropriate sensory stimulation and motor activations. So-called enriched sensory environments have been shown to be beneficial for cognitive development and enriched acoustic environment may even slow the progression of age-related hearing loss. It is possible that the beneficial effect of physical exercise is achieved through activation of neural plasticity. The beneficial effect of training after trauma to the brain or spinal cord is mainly achieved through shifting functions from damaged brain area to other parts of the central nervous system and adapting these parts to take over the functions that are lost. This is accomplished through activation of neural plasticity. Plastic changes can also be harmful and cause symptoms and signs of disorders such as some forms of chronic pain (central neuropathic pain) and severe tinnitus. We will call such disorders ``plasticity disorders".

  16. Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

    PubMed Central

    Bond, Allison M.; Ming, Guo-li; Song, Hongjun

    2015-01-01

    Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

  17. Epilepsy as an Example of Neural Plasticity

    PubMed Central

    Scharfman, Helen E.

    2008-01-01

    Epilepsy is a devastating disease affecting more than 1% of the population. Yet, if one considers the neurobiological substrates of this disease, what is revealed is an array of phenomenon that exemplify the remarkable capacity for the brain to change its basic structure and function, that is, neural plasticity. Some of these alterations are transient and merely impressive for their extent, or for their robust nature across animal models and human epilepsy. Others are notable for their persistence, often enduring for months or years. As an example, the dentate gyrus, and specifically the principal cell of the dentate gyrus, the granule cell, is highlighted. This area of the brain and this particular cell type, for reasons that are currently unclear, hold an uncanny capacity to change after seizures. For those interested in plasticity, it is suggested that perhaps the best examples for study of plasticity lie in the field of epilepsy. PMID:11954560

  18. A cortical disinhibitory circuit for enhancing adult plasticity.

    PubMed

    Fu, Yu; Kaneko, Megumi; Tang, Yunshuo; Alvarez-Buylla, Arturo; Stryker, Michael P

    2015-01-27

    The adult brain continues to learn and can recover from injury, but the elements and operation of the neural circuits responsible for this plasticity are not known. In previous work, we have shown that locomotion dramatically enhances neural activity in the visual cortex (V1) of the mouse (Niell and Stryker, 2010), identified the cortical circuit responsible for this enhancement (Fu et al., 2014), and shown that locomotion also dramatically enhances adult plasticity (Kaneko and Stryker, 2014). The circuit that is responsible for enhancing neural activity in the visual cortex contains both vasoactive intestinal peptide (VIP) and somatostatin (SST) neurons (Fu et al., 2014). Here, we ask whether this VIP-SST circuit enhances plasticity directly, independent of locomotion and aerobic activity. Optogenetic activation or genetic blockade of this circuit reveals that it is both necessary and sufficient for rapidly increasing V1 cortical responses following manipulation of visual experience in adult mice. These findings reveal a disinhibitory circuit that regulates adult cortical plasticity.

  19. Vertebrate Neural Stem Cells: Development, Plasticity, and Regeneration.

    PubMed

    Shimazaki, Takuya

    2016-01-01

    Natural recovery from disease and damage in the adult mammalian central nervous system (CNS) is limited compared with that in lower vertebrate species, including fish and salamanders. Species-specific differences in the plasticity of the CNS reflect these differences in regenerative capacity. Despite numerous extensive studies in the field of CNS regeneration, our understanding of the molecular mechanisms determining the regenerative capacity of the CNS is still relatively poor. The discovery of adult neural stem cells (aNSCs) in mammals, including humans, in the early 1990s has opened up new possibilities for the treatment of CNS disorders via self-regeneration through the mobilization of these cells. However, we now know that aNSCs in mammals are not plastic enough to induce significant regeneration. In contrast, aNSCs in some regenerative species have been found to be as highly plastic as early embryonic neural stem cells (NSCs). We must expand our knowledge of NSCs and of regenerative processes in lower vertebrates in an effort to develop effective regenerative treatments for damaged CNS in humans.

  20. Autonomic cardiac innervation: development and adult plasticity.

    PubMed

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these "non-classical" cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  1. Neural Plastic Effects of Cognitive Training on Aging Brain.

    PubMed

    Leung, Natalie T Y; Tam, Helena M K; Chu, Leung W; Kwok, Timothy C Y; Chan, Felix; Lam, Linda C W; Woo, Jean; Lee, Tatia M C

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  2. How Do Astrocytes Participate in Neural Plasticity?

    PubMed Central

    Haydon, Philip G.; Nedergaard, Maiken

    2015-01-01

    Work over the past 20 years has implicated electrically nonexcitable astrocytes in complex neural functions. Despite controversies, it is increasingly clear that many, if not all, neural processes involve astrocytes. This review critically examines past work to identify the commonalities among the many published studies of neuroglia signaling. Although several studies have shown that astrocytes can impact short-term and long-term synaptic plasticity, further work is required to determine the requirement for astrocytic Ca2+ and other second messengers in these processes. One of the roadblocks to the field advancing at a rapid pace has been technical. We predict that the novel experimental tools that have emerged in recent years will accelerate the field and likely disclose an entirely novel path of neuroglia signaling within the near future. PMID:25502516

  3. Neural Plasticity in Fathers of Human Infants

    PubMed Central

    Kim, Pilyoung; Rigo, Paola; Mayes, Linda C.; Feldman, Ruth; Leckman, James F.; Swain, James E

    2014-01-01

    Fathering plays an important role in infants’ socioemotional and cognitive development. Previous studies have identified brain regions that are important for parenting behavior in human mothers. However, the neural basis of parenting in human fathers is largely unexplored. In the current longitudinal study, we investigated structural changes in fathers’ brains during the first four months postpartum using voxel-based morphometry (VBM) analysis. Biological fathers (n=16) with full-term, healthy infants were scanned at 2–4 weeks postpartum (Time 1) and at 12–16 weeks postpartum (Time 2). Fathers exhibited increases in gray matter volume in several neural regions involved in parental motivation, including the hypothalamus, amygdala and striatum and lateral prefrontal cortex. On the other hand, fathers exhibited decreases in gray matter volume in the orbitofrontal cortex, posterior cingulate cortex and insula. The findings provide evidence for neural plasticity in fathers’ brains. We also discuss the distinct patterns of associations among neural changes, postpartum mood symptoms, and parenting behaviors among fathers. PMID:24958358

  4. Ubiquitous and temperature-dependent neural plasticity in hibernators.

    PubMed

    von der Ohe, Christina G; Darian-Smith, Corinna; Garner, Craig C; Heller, H Craig

    2006-10-11

    Hibernating mammals are remarkable for surviving near-freezing brain temperatures and near cessation of neural activity for a week or more at a time. This extreme physiological state is associated with dendritic and synaptic changes in hippocampal neurons. Here, we investigate whether these changes are a ubiquitous phenomenon throughout the brain that is driven by temperature. We iontophoretically injected Lucifer yellow into several types of neurons in fixed slices from hibernating ground squirrels. We analyzed neuronal microstructure from animals at several stages of torpor at two different ambient temperatures, and during the summer. We show that neuronal cell bodies, dendrites, and spines from several cell types in hibernating ground squirrels retract on entry into torpor, change little over the course of several days, and then regrow during the 2 h return to euthermia. Similar structural changes take place in neurons from the hippocampus, cortex, and thalamus, suggesting a global phenomenon. Investigation of neural microstructure from groups of animals hibernating at different ambient temperatures revealed that there is a linear relationship between neural retraction and minimum body temperature. Despite significant temperature-dependent differences in extent of retraction during torpor, recovery reaches the same final values of cell body area, dendritic arbor complexity, and spine density. This study demonstrates large-scale and seemingly ubiquitous neural plasticity in the ground squirrel brain during torpor. It also defines a temperature-driven model of dramatic neural plasticity, which provides a unique opportunity to explore mechanisms of large-scale regrowth in adult mammals, and the effects of remodeling on learning and memory.

  5. Neural Plasticity and Neurorehabilitation: Teaching the New Brain Old Tricks

    ERIC Educational Resources Information Center

    Kleim, Jeffrey A.

    2011-01-01

    Following brain injury or disease there are widespread biochemical, anatomical and physiological changes that result in what might be considered a new, very different brain. This adapted brain is forced to reacquire behaviors lost as a result of the injury or disease and relies on neural plasticity within the residual neural circuits. The same…

  6. Neural plasticity and implications for hand rehabilitation after neurological insult.

    PubMed

    Westlake, Kelly P; Byl, Nancy N

    2013-01-01

    Experience dependent plasticity refers to ability of the brain to adapt to new experiences by changing its structure and function. The purpose of this paper is to provide a brief review the neurophysiological and structural correlates of neural plasticity that occur during and following motor learning. We also consider that the extent of plastic reorganization is dependent upon several key principals and that the resulting behavioral consequences can be adaptive or maladaptive. In light of this research, we conclude that an increased understanding of the complexities of brain plasticity will translate into enhanced treatment opportunities for the clinician to optimize hand function.

  7. The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex

    PubMed Central

    Pan, Zhenxiang

    2017-01-01

    Neural plasticity, a fundamental mechanism of neuronal adaptation, is disrupted in depression. The changes in neural plasticity induced by stress and other negative stimuli play a significant role in the onset and development of depression. Antidepressant treatments have also been found to exert their antidepressant effects through regulatory effects on neural plasticity. However, the detailed mechanisms of neural plasticity in depression still remain unclear. Therefore, in this review, we summarize the recent literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these findings may pave the way for future progress in neural plasticity studies. PMID:28246558

  8. Early Cross-modal Plasticity in Adults.

    PubMed

    Lo Verde, Luca; Morrone, Maria Concetta; Lunghi, Claudia

    2017-03-01

    It is known that, after a prolonged period of visual deprivation, the adult visual cortex can be recruited for nonvisual processing, reflecting cross-modal plasticity. Here, we investigated whether cross-modal plasticity can occur at short timescales in the typical adult brain by comparing the interaction between vision and touch during binocular rivalry before and after a brief period of monocular deprivation, which strongly alters ocular balance favoring the deprived eye. While viewing dichoptically two gratings of orthogonal orientation, participants were asked to actively explore a haptic grating congruent in orientation to one of the two rivalrous stimuli. We repeated this procedure before and after 150 min of monocular deprivation. We first confirmed that haptic stimulation interacted with vision during rivalry promoting dominance of the congruent visuo-haptic stimulus and that monocular deprivation increased the deprived eye and decreased the nondeprived eye dominance. Interestingly, after deprivation, we found that the effect of touch did not change for the nondeprived eye, whereas it disappeared for the deprived eye, which was potentiated after deprivation. The absence of visuo-haptic interaction for the deprived eye lasted for over 1 hr and was not attributable to a masking induced by the stronger response of the deprived eye as confirmed by a control experiment. Taken together, our results demonstrate that the adult human visual cortex retains a high degree of cross-modal plasticity, which can occur even at very short timescales.

  9. Shaping the learning curve: epigenetic dynamics in neural plasticity

    PubMed Central

    Bronfman, Zohar Z.; Ginsburg, Simona; Jablonka, Eva

    2014-01-01

    A key characteristic of learning and neural plasticity is state-dependent acquisition dynamics reflected by the non-linear learning curve that links increase in learning with practice. Here we propose that the manner by which epigenetic states of individual cells change during learning contributes to the shape of the neural and behavioral learning curve. We base our suggestion on recent studies showing that epigenetic mechanisms such as DNA methylation, histone acetylation, and RNA-mediated gene regulation are intimately involved in the establishment and maintenance of long-term neural plasticity, reflecting specific learning-histories and influencing future learning. Our model, which is the first to suggest a dynamic molecular account of the shape of the learning curve, leads to several testable predictions regarding the link between epigenetic dynamics at the promoter, gene-network, and neural-network levels. This perspective opens up new avenues for therapeutic interventions in neurological pathologies. PMID:25071483

  10. Computational modeling of neural plasticity for self-organization of neural networks.

    PubMed

    Chrol-Cannon, Joseph; Jin, Yaochu

    2014-11-01

    Self-organization in biological nervous systems during the lifetime is known to largely occur through a process of plasticity that is dependent upon the spike-timing activity in connected neurons. In the field of computational neuroscience, much effort has been dedicated to building up computational models of neural plasticity to replicate experimental data. Most recently, increasing attention has been paid to understanding the role of neural plasticity in functional and structural neural self-organization, as well as its influence on the learning performance of neural networks for accomplishing machine learning tasks such as classification and regression. Although many ideas and hypothesis have been suggested, the relationship between the structure, dynamics and learning performance of neural networks remains elusive. The purpose of this article is to review the most important computational models for neural plasticity and discuss various ideas about neural plasticity's role. Finally, we suggest a few promising research directions, in particular those along the line that combines findings in computational neuroscience and systems biology, and their synergetic roles in understanding learning, memory and cognition, thereby bridging the gap between computational neuroscience, systems biology and computational intelligence.

  11. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  12. Models of Neural Plasticity and Classroom Practice.

    ERIC Educational Resources Information Center

    Brown, Dawn L.; Wheatley, Grayson H.

    The purpose of this paper is to explore the relationship between constructivism and neural organization. Support is given for a constructivist epistemology in current brain theory. A brief description of constructivism is provided, followed by the implication of this set of beliefs for viewing humans as self-organizing systems. What has been…

  13. Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex

    PubMed Central

    Ruiz-Perera, L.; Muniz, M.; Vierci, G.; Bornia, N.; Baroncelli, L.; Sale, A.; Rossi, F.M.

    2015-01-01

    The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals. The molecular mechanisms underlying this effect remain largely unknown. Here, we explored fluoxetine effects on mouse visual cortical plasticity, and exploited a proteomic approach to identify possible candidates mediating the outcome of the antidepressant treatment on adult cortical plasticity. We showed that fluoxetine restores ocular dominance plasticity in the adult mouse visual cortex, and identified 31 differentially expressed protein spots in fluoxetine-treated animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by bioinformatics analysis revealed that these proteins are involved in the control of cytoskeleton organization, endocytosis, molecular transport, intracellular signaling, redox cellular state, metabolism and protein degradation. Altogether, these results indicate a complex effect of fluoxetine on neuronal signaling mechanisms potentially involved in restoring plasticity in the adult brain. PMID:26205348

  14. Training-Induced Plasticity of Auditory Localization in Adult Mammals

    PubMed Central

    Kacelnik, Oliver; Nodal, Fernando R; Parsons, Carl H

    2006-01-01

    Accurate auditory localization relies on neural computations based on spatial cues present in the sound waves at each ear. The values of these cues depend on the size, shape, and separation of the two ears and can therefore vary from one individual to another. As with other perceptual skills, the neural circuits involved in spatial hearing are shaped by experience during development and retain some capacity for plasticity in later life. However, the factors that enable and promote plasticity of auditory localization in the adult brain are unknown. Here we show that mature ferrets can rapidly relearn to localize sounds after having their spatial cues altered by reversibly occluding one ear, but only if they are trained to use these cues in a behaviorally relevant task, with greater and more rapid improvement occurring with more frequent training. We also found that auditory adaptation is possible in the absence of vision or error feedback. Finally, we show that this process involves a shift in sensitivity away from the abnormal auditory spatial cues to other cues that are less affected by the earplug. The mature auditory system is therefore capable of adapting to abnormal spatial information by reweighting different localization cues. These results suggest that training should facilitate acclimatization to hearing aids in the hearing impaired. PMID:16509769

  15. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  16. Mechanisms for modulation of neural plasticity and axon regeneration by chondroitin sulphate.

    PubMed

    Miyata, Shinji; Kitagawa, Hiroshi

    2015-01-01

    Chondroitin sulphate proteoglycans (CSPGs), consisting of core proteins linked to one or more chondroitin sulphate (CS) chains, are major extracellular matrix (ECM) components of the central nervous system (CNS). Multi-functionality of CSPGs can be explained by the diversity in structure of CS chains that undergo dynamic changes during development and under pathological conditions. CSPGs, together with other ECM components, form mesh-like structures called perineuronal nets around a subset of neurons. Enzymatic digestion or genetic manipulation of CSPGs reactivates neural plasticity in the adult brain and improves regeneration of damaged axons after CNS injury. Recent studies have shown that CSPGs not only act as non-specific physical barriers that prevent rearrangement of synaptic connections but also regulate neural plasticity through specific interaction of CS chains with its binding partners in a manner that depends on the structure of the CS chain.

  17. The Neural Cell Adhesion Molecule-Derived Peptide FGL Facilitates Long-Term Plasticity in the Dentate Gyrus in Vivo

    ERIC Educational Resources Information Center

    Dallerac, Glenn; Zerwas, Meike; Novikova, Tatiana; Callu, Delphine; Leblanc-Veyrac, Pascale; Bock, Elisabeth; Berezin, Vladimir; Rampon, Claire; Doyere, Valerie

    2011-01-01

    The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as…

  18. Simulating dynamic plastic continuous neural networks by finite elements.

    PubMed

    Joghataie, Abdolreza; Torghabehi, Omid Oliyan

    2014-08-01

    We introduce dynamic plastic continuous neural network (DPCNN), which is comprised of neurons distributed in a nonlinear plastic medium where wire-like connections of neural networks are replaced with the continuous medium. We use finite element method to model the dynamic phenomenon of information processing within the DPCNNs. During the training, instead of weights, the properties of the continuous material at its different locations and some properties of neurons are modified. Input and output can be vectors and/or continuous functions over lines and/or areas. Delay and feedback from neurons to themselves and from outputs occur in the DPCNNs. We model a simple form of the DPCNN where the medium is a rectangular plate of bilinear material, and the neurons continuously fire a signal, which is a function of the horizontal displacement.

  19. Conservative motor systems, behavioral modulation and neural plasticity.

    PubMed

    Pellis, Sergio M

    2010-12-06

    Neural plasticity is a term that encompasses a vast array of changes in the nervous system in response to a wide range of environmental disturbances. The conservative manner in which nervous systems produce behavior is explored in the act of scratching the head. Whether the scratching is done with the hind leg (flamingos and axis deer) or the hand (spider monkey), it is shown that, when scratching their heads, animals follow a simple rule to avoid making multiple movements simultaneously with different parts of their bodies. Closer inspection of such a computational cost-saving scheme reveals that neural plasticity may best enhance motor performance when it occurs at higher levels of brain organization. The example of how complex social behavior, play fighting, is organized in rats shows that cortical systems can modify the contextual use of species-typical, or well-learned, behavior patterns, rather than producing new behavior patterns.

  20. Neural Plasticity in Common Forms of Chronic Headaches

    PubMed Central

    Lai, Tzu-Hsien; Protsenko, Ekaterina; Cheng, Yu-Chen; Loggia, Marco L.; Coppola, Gianluca; Chen, Wei-Ta

    2015-01-01

    Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache. PMID:26366304

  1. Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.

    PubMed

    Stokowska, Anna; Atkins, Alison L; Morán, Javier; Pekny, Tulen; Bulmer, Linda; Pascoe, Michaela C; Barnum, Scott R; Wetsel, Rick A; Nilsson, Jonas A; Dragunow, Mike; Pekna, Marcela

    2017-02-01

    Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.

  2. Neural ECM molecules in synaptic plasticity, learning, and memory.

    PubMed

    Senkov, Oleg; Andjus, Pavle; Radenovic, Lidija; Soriano, Eduardo; Dityatev, Alexander

    2014-01-01

    Neural extracellular matrix (ECM) molecules derived from neurons and glial cells accumulate in the extracellular space and regulate synaptic plasticity through modulation of perisomal GABAergic inhibition, intrinsic neuronal excitability, integrin signaling, and activities of L-type Ca(2+) channels, NMDA receptors, and Rho-associated kinase. Genetic or enzymatic targeting of ECM molecules proved to bidirectionally modulate acquisition of memories, depending on experimental conditions, and to promote cognitive flexibility and extinction of fear and drug memories. Furthermore, evidence is accumulating that dysregulation of ECM is linked to major psychiatric and neurodegenerative diseases and that targeting ECM molecules may rescue cognitive deficits in animal models of these diseases. Thus, the ECM emerged as a key component of synaptic plasticity, learning, and memory and as an attractive target for developing new generation of synapse plasticizing drugs.

  3. Neural plasticity and network remodeling: From concepts to pathology.

    PubMed

    Cohen, Erez James; Quarta, Eros; Bravi, Riccardo; Granato, Alberto; Minciacchi, Diego

    2017-03-06

    Neuroplasticity has been subject to a great deal of research in the last century. Recently, significant emphasis has been placed on the global effect of localized plastic changes throughout the central nervous system, and on how these changes integrate in a pathological context. Specifically, alterations of network functionality have been described in various pathological contexts to which corresponding structural alterations have been proposed. However, considering the amount of literature and the different pathological contexts, an integration of this information is still lacking. In this paper we will review the concepts of neural plasticity as well as their repercussions on network remodeling and provide a possible explanation to how these two concepts relate to each other. We will further examine how alterations in different pathological contexts may relate to each other and will discuss the concept of plasticity diseases, its models and implications.

  4. Immune Influence on Adult Neural Stem Cell Regulation and Function

    PubMed Central

    Carpentier, Pamela A.; Palmer, Theo D.

    2009-01-01

    Neural stem cells (NSCs) lie at the heart of central nervous system development and repair, and deficiency or dysregulation of NSCs or their progeny can have significant consequences at any stage of life. Immune signaling is emerging as one of the influential variables that define resident NSC behavior. Perturbations in local immune signaling accompany virtually every injury or disease state and signaling cascades that mediate immune activation, resolution, or chronic persistence influence resident stem and progenitor cells. Some aspects of immune signaling are beneficial, promoting intrinsic plasticity and cell replacement, while others appear to inhibit the very type of regenerative response that might restore or replace neural networks lost in injury or disease. Here we review known and speculative roles that immune signaling plays in the postnatal and adult brain, focusing on how environments encountered in disease or injury may influence the activity and fate of endogenous or transplanted NSCs. PMID:19840551

  5. The Effects of Leptin Replacement on Neural Plasticity.

    PubMed

    Paz-Filho, Gilberto J

    2016-01-01

    Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.

  6. Adult cortical plasticity following injury: Recapitulation of critical period mechanisms?

    PubMed Central

    Nahmani, Marc; Turrigiano, Gina G.

    2014-01-01

    A primary goal of research on developmental critical periods is the recapitulation of a juvenile-like state of malleability in the adult brain that might enable recovery from injury. These ambitions are often framed in terms of the simple reinstatement of enhanced plasticity in the growth-restricted milieu of an injured adult brain. Here, we provide an analysis of the similarities and differences between deprivation-induced and injury-induced cortical plasticity, to provide for a nuanced comparison of these remarkably similar processes. As a first step, we review the factors that drive ocular dominance plasticity in the primary visual cortex of the uninjured brain during the critical period (CP) and in adults, to highlight processes that might confer adaptive advantage. In addition, we directly compare deprivation-induced cortical plasticity during the CP and plasticity following acute injury or ischemia in mature brain. We find that these two processes display a biphasic response profile following deprivation or injury: an initial decrease in GABAergic inhibition and synapse loss transitions into a period of neurite expansion and synaptic gain. This biphasic response profile emphasizes the transition from a period of cortical healing to one of reconnection and recovery of function. Yet while injury-induced plasticity in adult shares several salient characteristics with deprivation-induced plasticity during the CP, the degree to which the adult injured brain is able to functionally rewire, and the time required to do so, present major limitations for recovery. Attempts to recapitulate a measure of CP plasticity in an adult injury context will need to carefully dissect the circuit alterations and plasticity mechanisms involved while measuring functional behavioral output to assess their ultimate success. PMID:24791715

  7. Pushing the Limits: Cognitive, Affective, and Neural Plasticity Revealed by an Intensive Multifaceted Intervention

    PubMed Central

    Mrazek, Michael D.; Mooneyham, Benjamin W.; Mrazek, Kaita L.; Schooler, Jonathan W.

    2016-01-01

    Scientific understanding of how much the adult brain can be shaped by experience requires examination of how multiple influences combine to elicit cognitive, affective, and neural plasticity. Using an intensive multifaceted intervention, we discovered that substantial and enduring improvements can occur in parallel across multiple cognitive and neuroimaging measures in healthy young adults. The intervention elicited substantial improvements in physical health, working memory, standardized test performance, mood, self-esteem, self-efficacy, mindfulness, and life satisfaction. Improvements in mindfulness were associated with increased degree centrality of the insula, greater functional connectivity between insula and somatosensory cortex, and reduced functional connectivity between posterior cingulate cortex (PCC) and somatosensory cortex. Improvements in working memory and reading comprehension were associated with increased degree centrality of a region within the middle temporal gyrus (MTG) that was extensively and predominately integrated with the executive control network. The scope and magnitude of the observed improvements represent the most extensive demonstration to date of the considerable human capacity for change. These findings point to higher limits for rapid and concurrent cognitive, affective, and neural plasticity than is widely assumed. PMID:27047361

  8. Cross-modal synaptic plasticity in adult primary sensory cortices.

    PubMed

    Lee, Hey-Kyoung; Whitt, Jessica L

    2015-12-01

    Sensory loss leads to widespread adaptation of brain circuits to allow an organism to navigate its environment with its remaining senses, which is broadly referred to as cross-modal plasticity. Such adaptation can be observed even in the primary sensory cortices, and falls into two distinct categories: recruitment of the deprived sensory cortex for processing the remaining senses, which we term 'cross-modal recruitment', and experience-dependent refinement of the spared sensory cortices referred to as 'compensatory plasticity.' Here we will review recent studies demonstrating that cortical adaptation to sensory loss involves LTP/LTD and homeostatic synaptic plasticity. Cross-modal synaptic plasticity is observed in adults, hence cross-modal sensory deprivation may be an effective way to promote plasticity in adult primary sensory cortices.

  9. Roles of neural stem cells and adult neurogenesis in adolescent alcohol use disorders.

    PubMed

    Nixon, Kimberly; Morris, Stephanie A; Liput, Daniel J; Kelso, Matthew L

    2010-02-01

    This review discusses the contributions of a newly considered form of plasticity, the ongoing production of new neurons from neural stem cells, or adult neurogenesis, within the context of neuropathologies that occur with excessive alcohol intake in the adolescents. Neural stem cells and adult neurogenesis are now thought to contribute to the structural integrity of the hippocampus, a limbic system region involved in learning, memory, behavioral control, and mood. In adolescents with alcohol use disorders (AUDs), the hippocampus appears to be particularly vulnerable to the neurodegenerative effects of alcohol, but the role of neural stem cells and adult neurogenesis in alcoholic neuropathology has only recently been considered. This review encompasses a brief overview of neural stem cells and the processes involved in adult neurogenesis, how neural stem cells are affected by alcohol, and possible differences in the neurogenic niche between adults and adolescents. Specifically, what is known about developmental differences in adult neurogenesis between the adult and adolescent is gleaned from the literature, as well as how alcohol affects this process differently among the age groups. Finally, this review suggests differences that may exist in the neurogenic niche between adults and adolescents and how these differences may contribute to the susceptibility of the adolescent hippocampus to damage. However, many more studies are needed to discern whether these developmental differences contribute to the vulnerability of the adolescent to developing an AUD.

  10. Cognitive correlates of visual neural plasticity in schizophrenia.

    PubMed

    Jahshan, Carol; Wynn, Jonathan K; Mathalon, Daniel H; Green, Michael F

    2017-03-20

    Neuroplasticity may be an important treatment target to improve the cognitive deficits in schizophrenia (SZ). Yet, it is poorly understood and difficult to assess. Recently, a visual high-frequency stimulation (HFS) paradigm that potentiates electroencephalography (EEG)-based visual evoked potentials (VEP) has been developed to assess neural plasticity in the visual cortex. Using this paradigm, we examined visual plasticity in SZ patients (N=64) and its correlations with clinical symptoms, neurocognition, functional capacity, and community functioning. VEPs were assessed prior to (baseline), and 2-, 4-, and 20-min after (Post-1, Post-2, and Post-3, respectively) 2min of visual HFS. Cluster-based permutation tests were conducted to identify time points and electrodes at which VEP amplitudes were significantly different after HFS. Compared to baseline, there was increased negativity between 140 and 227ms for the early post-HFS block (average of Post-1 and Post-2), and increased positivity between 180 and 281ms for the late post-HFS block (Post-3), at parieto-occipital and occipital electrodes. The increased negativity in the early post-HFS block did not correlate with any of the measures, whereas increased positivity in the late post-HFS block correlated with better neurocognitive performance. Results suggest that SZ patients exhibit both short- and long-term plasticity. The long-term plasticity effect, which was present 22min after HFS, was evident relatively late in the VEP, suggesting that neuroplastic changes in higher-order visual association areas, rather than earlier short-term changes in primary and secondary visual cortex, may be particularly important for the maintenance of neurocognitive function in SZ.

  11. Aging microglia: relevance to cognition and neural plasticity.

    PubMed

    Kohman, Rachel A

    2012-01-01

    Over the years it has become evident that the immune system can affect the function of the central nervous system (CNS), including altering cognitive processes. The impact of immune activation on the CNS is particularly important for aged individuals, as the brain's resident immune cells, microglia, acquire a pro-inflammatory profile. The low-grade chronic neuroinflammation that develops with normal aging likely contributes to the susceptibility to cognitive deficits and a host of age-related pathologies. Understanding why microglia show increased inflammatory activity (i.e., neuroinflammation) and identifying effective treatments to reduce microglia activation is expected to have beneficial effects on cognitive performance and measures of neural plasticity. However, microglia also promote regeneration after injury. Therefore, effective treatments must dampen inflammatory activity while preserving microglia's neuroprotective function. Discovering factors that induce neuroinflammation and investigating potential preventative therapies is expected to uncover the ways of maintaining normal microglia activity in the aged brain.

  12. Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation

    PubMed Central

    Furlan, Leonardo; Conforto, Adriana Bastos; Cohen, Leonardo G.; Sterr, Annette

    2016-01-01

    Advances in our understanding of the neural plasticity that occurs after hemiparetic stroke have contributed to the formulation of theories of poststroke motor recovery. These theories, in turn, have underpinned contemporary motor rehabilitation strategies for treating motor deficits after stroke, such as upper limb hemiparesis. However, a relative drawback has been that, in general, these strategies are most compatible with the recovery profiles of relatively high-functioning stroke survivors and therefore do not easily translate into benefit to those individuals sustaining low-functioning upper limb hemiparesis, who otherwise have poorer residual function. For these individuals, alternative motor rehabilitation strategies are currently needed. In this paper, we will review upper limb immobilisation studies that have been conducted with healthy adult humans and animals. Then, we will discuss how the findings from these studies could inspire the creation of a neural plasticity model that is likely to be of particular relevance to the context of motor rehabilitation after stroke. For instance, as will be elaborated, such model could contribute to the development of alternative motor rehabilitation strategies for treating poststroke upper limb hemiparesis. The implications of the findings from those immobilisation studies for contemporary motor rehabilitation strategies will also be discussed and perspectives for future research in this arena will be provided as well. PMID:26843992

  13. Neural Mechanisms of Brain Plasticity with Complex Cognitive Training in Healthy Seniors

    PubMed Central

    Chapman, Sandra B.; Aslan, Sina; Spence, Jeffrey S.; Hart, John J.; Bartz, Elizabeth K.; Didehbani, Nyaz; Keebler, Molly W.; Gardner, Claire M.; Strain, Jeremy F.; DeFina, Laura F.; Lu, Hanzhang

    2015-01-01

    Complex mental activity induces improvements in cognition, brain function, and structure in animals and young adults. It is not clear to what extent the aging brain is capable of such plasticity. This study expands previous evidence of generalized cognitive gains after mental training in healthy seniors. Using 3 MRI-based measurements, that is, arterial spin labeling MRI, functional connectivity, and diffusion tensor imaging, we examined brain changes across 3 time points pre, mid, and post training (12 weeks) in a randomized sample (n = 37) who received cognitive training versus a control group. We found significant training-related brain state changes at rest; specifically, 1) increases in global and regional cerebral blood flow (CBF), particularly in the default mode network and the central executive network, 2) greater connectivity in these same networks, and 3) increased white matter integrity in the left uncinate demonstrated by an increase in fractional anisotropy. Improvements in cognition were identified along with significant CBF correlates of the cognitive gains. We propose that cognitive training enhances resting-state neural activity and connectivity, increasing the blood supply to these regions via neurovascular coupling. These convergent results provide preliminary evidence that neural plasticity can be harnessed to mitigate brain losses with cognitive training in seniors. PMID:23985135

  14. ADULT NEURAL STEM CELLS: RESPONSE TO STROKE INJURY AND POTENTIAL FOR THERAPEUTIC APPLICATIONS

    PubMed Central

    Barkho, Basam Z.; Zhao, Xinyu

    2011-01-01

    The plasticity of neural stem/progenitor cells allows a variety of different responses to many environmental cues. In the past decade, significant research has gone into understanding the regulation of neural stem/progenitor cell properties, because of their promise for cell replacement therapies in adult neurological diseases. Both endogenous and grafted neural stem/progenitor cells are known to have the ability to migrate long distances to lesioned sites after brain injury and differentiate into new neurons. Several chemokines and growth factors, including stromal cell-derived factor-1 and vascular endothelial growth factor, have been shown to stimulate the proliferation, differentiation, and migration of neural stem/progenitor cells, and investigators have now begun to identify the critical downstream effectors and signaling mechanisms that regulate these processes. Both our own lab and others have shown that the extracellular matrix and matrix remodeling factors play a critical role in directing cell differentiation and migration of adult neural stem/progenitor cells within injured sites. Identification of these and other molecular pathways involved in stem cell homing into ischemic areas is vital for the development of new treatments. To ensure the best functional recovery, regenerative therapy may require the application of a combination approach that includes cell replacement, trophic support, and neural protection. Here we review the current state of our knowledge about endogenous adult and exogenous neural stem/progenitor cells as potential therapeutic agents for central nervous system injuries. PMID:21466483

  15. Activity-Regulated Genes as Mediators of Neural Circuit Plasticity

    PubMed Central

    Leslie, Jennifer H.; Nedivi, Elly

    2011-01-01

    Modifications of neuronal circuits allow the brain to adapt and change with experience. This plasticity manifests during development and throughout life, and can be remarkably long lasting. Many electrophysiological and molecular mechanisms are common to the seemingly diverse types of activity-dependent functional adaptation that take place during developmental critical periods, learning and memory, and alterations to sensory map representations in the adult. Experience-dependent plasticity is triggered when neuronal excitation activates cellular signaling pathways from the synapse to the nucleus that initiate new programs of gene expression. The protein products of activity-regulated genes then work via a diverse array of cellular mechanisms to modify neuronal functional properties. They fine-tune brain circuits by strengthening or weakening synaptic connections or by altering synapse numbers. Their effects are further modulated by posttranscriptional regulatory mechanisms, often also dependent on activity, that control activity-regulated gene transcript and protein function. Thus, the cellular response to neuronal activity integrates multiple tightly coordinated mechanisms to precisely orchestrate long-lasting, functional and structural changes in brain circuits. PMID:21601615

  16. Rehabilitation with Poststroke Motor Recovery: A Review with a Focus on Neural Plasticity

    PubMed Central

    Takeuchi, Naoyuki; Izumi, Shin-Ichi

    2013-01-01

    Motor recovery after stroke is related to neural plasticity, which involves developing new neuronal interconnections, acquiring new functions, and compensating for impairment. However, neural plasticity is impaired in the stroke-affected hemisphere. Therefore, it is important that motor recovery therapies facilitate neural plasticity to compensate for functional loss. Stroke rehabilitation programs should include meaningful, repetitive, intensive, and task-specific movement training in an enriched environment to promote neural plasticity and motor recovery. Various novel stroke rehabilitation techniques for motor recovery have been developed based on basic science and clinical studies of neural plasticity. However, the effectiveness of rehabilitative interventions among patients with stroke varies widely because the mechanisms underlying motor recovery are heterogeneous. Neurophysiological and neuroimaging studies have been developed to evaluate the heterogeneity of mechanisms underlying motor recovery for effective rehabilitation interventions after stroke. Here, we review novel stroke rehabilitation techniques associated with neural plasticity and discuss individualized strategies to identify appropriate therapeutic goals, prevent maladaptive plasticity, and maximize functional gain in patients with stroke. PMID:23738231

  17. Hunting increases adaptive auditory map plasticity in adult barn owls.

    PubMed

    Bergan, Joseph F; Ro, Peter; Ro, Daniel; Knudsen, Eric I

    2005-10-19

    The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.

  18. Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity

    PubMed Central

    Warlaumont, Anne S.; Finnegan, Megan K.

    2016-01-01

    At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant’s nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model’s frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one’s own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing-dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop

  19. Noradrenergic regulation of plasticity marker expression in the adult rodent piriform cortex.

    PubMed

    Vadodaria, Krishna C; Yanpallewar, Sudhirkumar U; Vadhvani, Mayur; Toshniwal, Devyani; Liles, L Cameron; Rommelfanger, Karen S; Weinshenker, David; Vaidya, Vidita A

    2017-02-23

    The adult rodent piriform cortex has been reported to harbor immature neurons that express markers associated with neurodevelopment and plasticity, namely polysialylated neural cell adhesion molecule (PSA-NCAM) and doublecortin (DCX). We characterized the expression of PSA-NCAM and DCX across the rostrocaudal axis of the rat piriform cortex and observed higher numbers of PSA-NCAM and DCX positive cells in the posterior subdivision. As observed in the rat piriform cortex, Nestin-GFP reporter mice also revealed a similar gradient of GFP-positive cells with an increasing rostro-caudal gradient of expression. Given the extensive noradrenergic innervation of the piriform cortex and its role in regulating piriform cortex function and synaptic plasticity, we addressed the influence of norepinephrine (NE) on piriform cortex plasticity marker expression. Depletion of NE by treatment with the noradrenergic neurotoxin DSP-4 significantly increased the number of DCX and PSA-NCAM immunopositive cells in the piriform cortex of adult rats. Similarly, DSP-4 treated Nestin-GFP reporter mice revealed a robust induction of GFP-positive cells within the piriform cortex following NE depletion. Genetic loss of NE in dopamine β-hydroxylase knockout (Dbh -/-) mice phenocopied the effects of DSP-4, with an increase noted in PSA-NCAM and DCX positive cells in the piriform cortex. Further, chronic α2-adrenergic receptor stimulation with the agonist guanabenz increased PSA-NCAM and DCX positive cells in the piriform cortex of adult rats and GFP-positive cells in the piriform cortex of Nestin-GFP mice. By contrast, chronic α2-adrenergic receptor blockade with the antagonist yohimbine reduced PSA-NCAM and DCX positive cells in the piriform cortex of adult rats. Our results provide novel evidence for a role of NE in regulating the expression of plasticity markers, including PSA-NCAM, DCX, and nestin, within the adult mouse and rat piriform cortex.

  20. Translating Principles of Neural Plasticity into Research on Speech Motor Control Recovery and Rehabilitation

    ERIC Educational Resources Information Center

    Ludlow, Christy L.; Hoit, Jeannette; Kent, Raymond; Ramig, Lorraine O.; Shrivastav, Rahul; Strand, Edythe; Yorkston, Kathryn; Sapienza, Christine M.

    2008-01-01

    Purpose: To review the principles of neural plasticity and make recommendations for research on the neural bases for rehabilitation of neurogenic speech disorders. Method: A working group in speech motor control and disorders developed this report, which examines the potential relevance of basic research on the brain mechanisms involved in neural…

  1. A Semi-Persistent Adult Ocular Dominance Plasticity in Visual Cortex Is Stabilized by Activated CREB

    ERIC Educational Resources Information Center

    Barco, Angel; Kandel, Eric R.; Gordon, Barbara; Lickey, Marvin E.; Suzuki, Seigo; Pham, Tony A.; Graham, Sarah J.

    2004-01-01

    The adult cerebral cortex can adapt to environmental change. Using monocular deprivation as a paradigm, we find that rapid experience-dependent plasticity exists even in the mature primary visual cortex. However, adult cortical plasticity differs from developmental plasticity in two important ways. First, the effect of adult, but not juvenile…

  2. Using brain-computer interfaces to induce neural plasticity and restore function

    NASA Astrophysics Data System (ADS)

    Grosse-Wentrup, Moritz; Mattia, Donatella; Oweiss, Karim

    2011-04-01

    Analyzing neural signals and providing feedback in realtime is one of the core characteristics of a brain-computer interface (BCI). As this feature may be employed to induce neural plasticity, utilizing BCI technology for therapeutic purposes is increasingly gaining popularity in the BCI community. In this paper, we discuss the state-of-the-art of research on this topic, address the principles of and challenges in inducing neural plasticity by means of a BCI, and delineate the problems of study design and outcome evaluation arising in this context. We conclude with a list of open questions and recommendations for future research in this field.

  3. Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets

    PubMed Central

    Dzyubenko, Egor; Gottschling, Christine

    2016-01-01

    Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system (CNS) and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix (ECM) components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets (PNNs). PNNs have originally been discovered by Golgi and represent a molecular scaffold deposited in the interface between the astrocyte and subsets of neurons in the vicinity of the synapse. Recent reports strongly suggest that PNNs are tightly involved in the regulation of synaptic plasticity. Moreover, several studies have implicated PNNs and the neural ECM in neuropsychiatric diseases. Here, we highlight current concepts relating to neural ECM and PNNs and describe an in vitro approach that allows for the investigation of ECM functions for synaptogenesis. PMID:26881114

  4. REST regulation of gene networks in adult neural stem cells

    PubMed Central

    Mukherjee, Shradha; Brulet, Rebecca; Zhang, Ling; Hsieh, Jenny

    2016-01-01

    Adult hippocampal neural stem cells generate newborn neurons throughout life due to their ability to self-renew and exist as quiescent neural progenitors (QNPs) before differentiating into transit-amplifying progenitors (TAPs) and newborn neurons. The mechanisms that control adult neural stem cell self-renewal are still largely unknown. Conditional knockout of REST (repressor element 1-silencing transcription factor) results in precocious activation of QNPs and reduced neurogenesis over time. To gain insight into the molecular mechanisms by which REST regulates adult neural stem cells, we perform chromatin immunoprecipitation sequencing and RNA-sequencing to identify direct REST target genes. We find REST regulates both QNPs and TAPs, and importantly, ribosome biogenesis, cell cycle and neuronal genes in the process. Furthermore, overexpression of individual REST target ribosome biogenesis or cell cycle genes is sufficient to induce activation of QNPs. Our data define novel REST targets to maintain the quiescent neural stem cell state. PMID:27819263

  5. REST regulation of gene networks in adult neural stem cells.

    PubMed

    Mukherjee, Shradha; Brulet, Rebecca; Zhang, Ling; Hsieh, Jenny

    2016-11-07

    Adult hippocampal neural stem cells generate newborn neurons throughout life due to their ability to self-renew and exist as quiescent neural progenitors (QNPs) before differentiating into transit-amplifying progenitors (TAPs) and newborn neurons. The mechanisms that control adult neural stem cell self-renewal are still largely unknown. Conditional knockout of REST (repressor element 1-silencing transcription factor) results in precocious activation of QNPs and reduced neurogenesis over time. To gain insight into the molecular mechanisms by which REST regulates adult neural stem cells, we perform chromatin immunoprecipitation sequencing and RNA-sequencing to identify direct REST target genes. We find REST regulates both QNPs and TAPs, and importantly, ribosome biogenesis, cell cycle and neuronal genes in the process. Furthermore, overexpression of individual REST target ribosome biogenesis or cell cycle genes is sufficient to induce activation of QNPs. Our data define novel REST targets to maintain the quiescent neural stem cell state.

  6. A Neural Circuit That Controls Cortical State, Plasticity, and the Gain of Sensory Responses in Mouse.

    PubMed

    Stryker, Michael P

    2014-01-01

    Neurons in the visual cortex were first found to be exquisitely selective for particular properties of visual stimuli in anesthetized animals, including mice. Studies of alert mice in an apparatus that allowed them to stand or run revealed that locomotion causes a change in cortical state that dramatically increases the magnitude of responses in neurons of the visual cortex without altering selectivity, effectively changing the gain of sensory responses. Locomotion also dramatically enhances adult plasticity in the recovery from long-term visual deprivation. We have studied the elements and operation of the neural circuit responsible for the enhancement of activity and shown that it enhances plasticity even in mice not free to run. The circuit consists of projections ascending from the midbrain locomotor region (MLR) to the basal forebrain, activating cholinergic and perhaps other projections to excite inhibitory interneurons expressing vasoactive intestinal peptide (VIP) in the visual cortex. VIP cells activated by locomotion inhibit interneurons that express somatostatin (SST), thereby disinhibiting the excitatory principal neurons and allowing them to respond more strongly to effective visual stimuli. These findings reveal in alert animals how the ascending reticular activating system described in anesthetized animals 50 years ago operates to control cortical state.

  7. Adult plasticity in the subcortical auditory pathway of the maternal mouse.

    PubMed

    Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

    2014-01-01

    Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

  8. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells].

    PubMed

    Dupin, Elisabeth

    2011-01-01

    Melanocytes, the pigmented cells of the skin, and the glial Schwann cells lining peripheral nerves are developmentally derived from an early and transient ectodermal structure of the vertebrate embryo, the neural crest, which is also at the origin of multiple neural and non-neural cell types. Besides melanocytes and neural cells of the peripheral nervous system, the neural crest cells give rise to mesenchymal cell types in the head, which form most of the craniofacial skeleton, dermis, fat tissue and vascular musculo-connective components. How such a wide diversity of differentiation fates is established during embryogenesis and is later maintained in adult tissues are among key questions in developmental and stem cell biology. The analysis of the developmental potentials of single neural crest cells cultured in vitro led to characterizing multipotent stem/progenitor cells as well as more restricted precursors in the early neural crest of avian and mammalian embryos. Data support a hierarchical model of the diversification of neural crest lineages through progressive restrictions of multipotent stem cell potentials driven by local environmental factors. In particular, melanocytes and glial Schwann cells were shown to arise from a common bipotent progenitor, which depends upon the peptide endothelin-3 for proliferation and self-renewal ability. In vivo, signaling by endothelin-3 and its receptor is also required for the early development of melanocytes and proper pigmentation of the vertebrate body. It is generally assumed that, after lineage specification and terminal differentiation, specialized cell types, like the melanocytes and Schwann cells, do not change their identity. However, this classic notion that somatic cell differentiation is a stable and irreversible process has been challenged by emerging evidence that dedifferentiation can occur in different biological systems through nuclear transfer, cell fusion, epigenetic modifications and ectopic gene

  9. The super-Turing computational power of plastic recurrent neural networks.

    PubMed

    Cabessa, Jérémie; Siegelmann, Hava T

    2014-12-01

    We study the computational capabilities of a biologically inspired neural model where the synaptic weights, the connectivity pattern, and the number of neurons can evolve over time rather than stay static. Our study focuses on the mere concept of plasticity of the model so that the nature of the updates is assumed to be not constrained. In this context, we show that the so-called plastic recurrent neural networks (RNNs) are capable of the precise super-Turing computational power--as the static analog neural networks--irrespective of whether their synaptic weights are modeled by rational or real numbers, and moreover, irrespective of whether their patterns of plasticity are restricted to bi-valued updates or expressed by any other more general form of updating. Consequently, the incorporation of only bi-valued plastic capabilities in a basic model of RNNs suffices to break the Turing barrier and achieve the super-Turing level of computation. The consideration of more general mechanisms of architectural plasticity or of real synaptic weights does not further increase the capabilities of the networks. These results support the claim that the general mechanism of plasticity is crucially involved in the computational and dynamical capabilities of biological neural networks. They further show that the super-Turing level of computation reflects in a suitable way the capabilities of brain-like models of computation.

  10. A framework for plasticity implementation on the SpiNNaker neural architecture

    PubMed Central

    Galluppi, Francesco; Lagorce, Xavier; Stromatias, Evangelos; Pfeiffer, Michael; Plana, Luis A.; Furber, Steve B.; Benosman, Ryad B.

    2015-01-01

    Many of the precise biological mechanisms of synaptic plasticity remain elusive, but simulations of neural networks have greatly enhanced our understanding of how specific global functions arise from the massively parallel computation of neurons and local Hebbian or spike-timing dependent plasticity rules. For simulating large portions of neural tissue, this has created an increasingly strong need for large scale simulations of plastic neural networks on special purpose hardware platforms, because synaptic transmissions and updates are badly matched to computing style supported by current architectures. Because of the great diversity of biological plasticity phenomena and the corresponding diversity of models, there is a great need for testing various hypotheses about plasticity before committing to one hardware implementation. Here we present a novel framework for investigating different plasticity approaches on the SpiNNaker distributed digital neural simulation platform. The key innovation of the proposed architecture is to exploit the reconfigurability of the ARM processors inside SpiNNaker, dedicating a subset of them exclusively to process synaptic plasticity updates, while the rest perform the usual neural and synaptic simulations. We demonstrate the flexibility of the proposed approach by showing the implementation of a variety of spike- and rate-based learning rules, including standard Spike-Timing dependent plasticity (STDP), voltage-dependent STDP, and the rate-based BCM rule. We analyze their performance and validate them by running classical learning experiments in real time on a 4-chip SpiNNaker board. The result is an efficient, modular, flexible and scalable framework, which provides a valuable tool for the fast and easy exploration of learning models of very different kinds on the parallel and reconfigurable SpiNNaker system. PMID:25653580

  11. A framework for plasticity implementation on the SpiNNaker neural architecture.

    PubMed

    Galluppi, Francesco; Lagorce, Xavier; Stromatias, Evangelos; Pfeiffer, Michael; Plana, Luis A; Furber, Steve B; Benosman, Ryad B

    2014-01-01

    Many of the precise biological mechanisms of synaptic plasticity remain elusive, but simulations of neural networks have greatly enhanced our understanding of how specific global functions arise from the massively parallel computation of neurons and local Hebbian or spike-timing dependent plasticity rules. For simulating large portions of neural tissue, this has created an increasingly strong need for large scale simulations of plastic neural networks on special purpose hardware platforms, because synaptic transmissions and updates are badly matched to computing style supported by current architectures. Because of the great diversity of biological plasticity phenomena and the corresponding diversity of models, there is a great need for testing various hypotheses about plasticity before committing to one hardware implementation. Here we present a novel framework for investigating different plasticity approaches on the SpiNNaker distributed digital neural simulation platform. The key innovation of the proposed architecture is to exploit the reconfigurability of the ARM processors inside SpiNNaker, dedicating a subset of them exclusively to process synaptic plasticity updates, while the rest perform the usual neural and synaptic simulations. We demonstrate the flexibility of the proposed approach by showing the implementation of a variety of spike- and rate-based learning rules, including standard Spike-Timing dependent plasticity (STDP), voltage-dependent STDP, and the rate-based BCM rule. We analyze their performance and validate them by running classical learning experiments in real time on a 4-chip SpiNNaker board. The result is an efficient, modular, flexible and scalable framework, which provides a valuable tool for the fast and easy exploration of learning models of very different kinds on the parallel and reconfigurable SpiNNaker system.

  12. Learning-induced synchronization and plasticity of a developing neural network.

    PubMed

    Chao, T C; Chen, C M

    2005-12-01

    Learning-induced synchronization of a neural network at various developing stages is studied by computer simulations using a pulse-coupled neural network model in which the neuronal activity is simulated by a one-dimensional map. Two types of Hebbian plasticity rules are investigated and their differences are compared. For both models, our simulations show a logarithmic increase in the synchronous firing frequency of the network with the culturing time of the neural network. This result is consistent with recent experimental observations. To investigate how to control the synchronization behavior of a neural network after learning, we compare the occurrence of synchronization for four networks with different designed patterns under the influence of an external signal. The effect of such a signal on the network activity highly depends on the number of connections between neurons. We discuss the synaptic plasticity and enhancement effects for a random network after learning at various developing stages.

  13. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks.

    PubMed

    Tonelli, Paul; Mouret, Jean-Baptiste

    2013-01-01

    A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2) synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT). Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1) in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2) whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities.

  14. Plasticity in memristive devices for spiking neural networks

    PubMed Central

    Saïghi, Sylvain; Mayr, Christian G.; Serrano-Gotarredona, Teresa; Schmidt, Heidemarie; Lecerf, Gwendal; Tomas, Jean; Grollier, Julie; Boyn, Sören; Vincent, Adrien F.; Querlioz, Damien; La Barbera, Selina; Alibart, Fabien; Vuillaume, Dominique; Bichler, Olivier; Gamrat, Christian; Linares-Barranco, Bernabé

    2015-01-01

    Memristive devices present a new device technology allowing for the realization of compact non-volatile memories. Some of them are already in the process of industrialization. Additionally, they exhibit complex multilevel and plastic behaviors, which make them good candidates for the implementation of artificial synapses in neuromorphic engineering. However, memristive effects rely on diverse physical mechanisms, and their plastic behaviors differ strongly from one technology to another. Here, we present measurements performed on different memristive devices and the opportunities that they provide. We show that they can be used to implement different learning rules whose properties emerge directly from device physics: real time or accelerated operation, deterministic or stochastic behavior, long term or short term plasticity. We then discuss how such devices might be integrated into a complete architecture. These results highlight that there is no unique way to exploit memristive devices in neuromorphic systems. Understanding and embracing device physics is the key for their optimal use. PMID:25784849

  15. Plasticity in memristive devices for spiking neural networks.

    PubMed

    Saïghi, Sylvain; Mayr, Christian G; Serrano-Gotarredona, Teresa; Schmidt, Heidemarie; Lecerf, Gwendal; Tomas, Jean; Grollier, Julie; Boyn, Sören; Vincent, Adrien F; Querlioz, Damien; La Barbera, Selina; Alibart, Fabien; Vuillaume, Dominique; Bichler, Olivier; Gamrat, Christian; Linares-Barranco, Bernabé

    2015-01-01

    Memristive devices present a new device technology allowing for the realization of compact non-volatile memories. Some of them are already in the process of industrialization. Additionally, they exhibit complex multilevel and plastic behaviors, which make them good candidates for the implementation of artificial synapses in neuromorphic engineering. However, memristive effects rely on diverse physical mechanisms, and their plastic behaviors differ strongly from one technology to another. Here, we present measurements performed on different memristive devices and the opportunities that they provide. We show that they can be used to implement different learning rules whose properties emerge directly from device physics: real time or accelerated operation, deterministic or stochastic behavior, long term or short term plasticity. We then discuss how such devices might be integrated into a complete architecture. These results highlight that there is no unique way to exploit memristive devices in neuromorphic systems. Understanding and embracing device physics is the key for their optimal use.

  16. Adult plasticity and cortical reorganization after peripheral lesions.

    PubMed

    Sammons, Rosanna P; Keck, Tara

    2015-12-01

    Following loss of input due to peripheral lesions, functional reorganization occurs in the deprived cortical region in adults. Over a period of hours to months, cells in the lesion projection zone (LPZ) begin to respond to novel stimuli. This reorganization is mediated by two processes: a reduction of inhibition in a gradient throughout the cortex and input remapping via sprouting of axonal arbors from cortical regions spatially adjacent to the LPZ, and strengthening of pre-existing subthreshold inputs. Together these inputs facilitate receptive field remapping of cells in the LPZ. Recent experiments have revealed time courses and potential interactions of the mechanisms associated with functional reorganization, suggesting that large scale reorganization in the adult may utilize plasticity mechanisms prominent during development.

  17. Childhood Social Inequalities Influences Neural Processes in Young Adult Caregiving

    PubMed Central

    Kim, Pilyoung; Ho, S. Shaun; Evans, Gary W.; Liberzon, Israel; Swain, James E.

    2016-01-01

    Childhood poverty is associated with harsh parenting with a risk of transmission to the next generation. This prospective study examined the relations between childhood poverty and non-parent adults’ neural responses to infant cry sounds. While no main effects of poverty were revealed in contrasts of infant cry vs. acoustically matched white noise, a gender by childhood poverty interaction emerged. In females, childhood poverty was associated with increased neural activations in the posterior insula, striatum, calcarine sulcus, hippocampus and fusiform gyrus, while, in males, childhood poverty was associated with reduced levels of neural responses to infant cry in the same regions. Irrespective of gender, neural activation in these regions was associated with higher levels of annoyance with the cry sound and reduced desire to approach the crying infant. The findings suggest gender differences in neural and emotional responses to infant cry sounds among young adults growing up in poverty. PMID:25981334

  18. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

    PubMed Central

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

  19. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background.

    PubMed

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets.

  20. Neural Plasticity and the Issue of Mimicry Tasks in L2 Pronunciation Studies.

    ERIC Educational Resources Information Center

    Stapp, Yvonne F.

    1999-01-01

    In an investigation of the relationship between mimicry skill and neural plasticity, 28 monolingual Japanese subjects aged 4-17 repeated a list of simple English words containing /r/ and /l/. Analyses were made of individual and age-group scores and of consistency of individuals' pronunciation across word tokens. Results indicated mimicry ability…

  1. Swallowing and Dysphagia Rehabilitation: Translating Principles of Neural Plasticity into Clinically Oriented Evidence

    ERIC Educational Resources Information Center

    Robbins, JoAnne; Butler, Susan G.; Daniels, Stephanie K.; Gross, Roxann Diez; Langmore, Susan; Lazarus, Cathy L.; Martin-Harris, Bonnie; McCabe, Daniel; Musson, Nan; Rosenbek, John

    2008-01-01

    Purpose: This review presents the state of swallowing rehabilitation science as it relates to evidence for neural plastic changes in the brain. The case is made for essential collaboration between clinical and basic scientists to expand the positive influences of dysphagia rehabilitation in synergy with growth in technology and knowledge. The…

  2. Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation after Brain Damage

    ERIC Educational Resources Information Center

    Kleim, Jeffrey A.; Jones, Theresa A.

    2008-01-01

    Purpose: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the…

  3. Multisensory dysfunction accompanies crossmodal plasticity following adult hearing impairment.

    PubMed

    Meredith, M A; Keniston, L P; Allman, B L

    2012-07-12

    Until now, cortical crossmodal plasticity has largely been regarded as the effect of early and complete sensory loss. Recently, massive crossmodal cortical reorganization was demonstrated to result from profound hearing loss in adult ferrets (Allman et al., 2009a). Moderate adult hearing loss, on the other hand, induced not just crossmodal reorganization, but also merged new crossmodal inputs with residual auditory function to generate multisensory neurons. Because multisensory convergence can lead to dramatic levels of response integration when stimuli from more than one modality are present (and thereby potentially interfere with residual auditory processing), the present investigation sought to evaluate the multisensory properties of auditory cortical neurons in partially deafened adult ferrets. When compared with hearing controls, partially-deaf animals revealed elevated spontaneous levels and a dramatic increase (∼2 times) in the proportion of multisensory cortical neurons, but few of which showed multisensory integration. Moreover, a large proportion (68%) of neurons with somatosensory and/or visual inputs was vigorously active in core auditory cortex in the absence of auditory stimulation. Collectively, these results not only demonstrate multisensory dysfunction in core auditory cortical neurons from hearing impaired adults but also reveal a potential cortical substrate for maladaptive perceptual effects such as tinnitus.

  4. The transformation of synaptic to system plasticity in motor output from the sacral cord of the adult mouse

    PubMed Central

    Elbasiouny, Sherif M.; Collins, William F.; Heckman, C. J.

    2015-01-01

    Synaptic plasticity is fundamental in shaping the output of neural networks. The transformation of synaptic plasticity at the cellular level into plasticity at the system level involves multiple factors, including behavior of local networks of interneurons. Here we investigate the synaptic to system transformation for plasticity in motor output in an in vitro preparation of the adult mouse spinal cord. System plasticity was assessed from compound action potentials (APs) in spinal ventral roots, which were generated simultaneously by the axons of many motoneurons (MNs). Synaptic plasticity was assessed from intracellular recordings of MNs. A computer model of the MN pool was used to identify the middle steps in the transformation from synaptic to system behavior. Two input systems that converge on the same MN pool were studied: one sensory and one descending. The two synaptic input systems generated very different motor outputs, with sensory stimulation consistently evoking short-term depression (STD) whereas descending stimulation had bimodal plasticity: STD at low frequencies but short-term facilitation (STF) at high frequencies. Intracellular and pharmacological studies revealed contributions from monosynaptic excitation and stimulus time-locked inhibition but also considerable asynchronous excitation sustained from local network activity. The computer simulations showed that STD in the monosynaptic excitatory input was the primary driver of the system STD in the sensory input whereas network excitation underlies the bimodal plasticity in the descending system. These results provide insight on the roles of plasticity in the monosynaptic and polysynaptic inputs converging on the same MN pool to overall motor plasticity. PMID:26203107

  5. Intrinsic Plasticity for Natural Competition in Koniocortex-Like Neural Networks.

    PubMed

    Peláez, Francisco Javier Ropero; Aguiar-Furucho, Mariana Antonia; Andina, Diego

    2016-08-01

    In this paper, we use the neural property known as intrinsic plasticity to develop neural network models that resemble the koniocortex, the fourth layer of sensory cortices. These models evolved from a very basic two-layered neural network to a complex associative koniocortex network. In the initial network, intrinsic and synaptic plasticity govern the shifting of the activation function, and the modification of synaptic weights, respectively. In this first version, competition is forced, so that the most activated neuron is arbitrarily set to one and the others to zero, while in the second, competition occurs naturally due to inhibition between second layer neurons. In the third version of the network, whose architecture is similar to the koniocortex, competition also occurs naturally owing to the interplay between inhibitory interneurons and synaptic and intrinsic plasticity. A more complex associative neural network was developed based on this basic koniocortex-like neural network, capable of dealing with incomplete patterns and ideally suited to operating similarly to a learning vector quantization network. We also discuss the biological plausibility of the networks and their role in a more complex thalamocortical model.

  6. Brain-Controlled Neuromuscular Stimulation to Drive Neural Plasticity and Functional Recovery

    PubMed Central

    Ethier, C.; Gallego, J.A.; Miller, L.E.

    2015-01-01

    There is mounting evidence that appropriately timed neuromuscular stimulation can induce neural plasticity and generate functional recovery from motor disorders. This review addresses the idea that coordinating stimulation with a patient’s voluntary effort might further enhance neurorehabilitation. Studies in cell cultures and behaving animals have delineated the rules underlying neural plasticity when single neurons are used as triggers. However, the rules governing more complex stimuli and larger networks are less well understood. We argue that functional recovery might be optimized if stimulation were modulated by a brain machine interface, to matched the details of the patient’s voluntary intent. The potential of this novel approach highlights the need for a better understanding of the complex rules underlying this form of plasticity. PMID:25827275

  7. Neural Plasticity and Neurorehabilitation Following Traumatic Brain Injury

    DTIC Science & Technology

    2011-04-01

    understood and has relied primarily on findings from studies conducted in stroke . We have demonstrated that following CCI (a rodent model of...expected based on stroke models. Despite this, the motor cortex near the contusion maintains the capacity for motor map plasticity. 15. SUBJECT TERMS...been extensively studied in animal models of stroke and have significantly influenced rehabilitation of stroke patients (for review see (T. A. Jones et

  8. Phylogenetic plasticity in the evolution of molluscan neural circuits.

    PubMed

    Katz, Paul S

    2016-12-01

    Recent research on molluscan nervous systems provides a unique perspective on the evolution of neural circuits. Molluscs evolved large, encephalized nervous systems independently from other phyla. Homologous body-patterning genes were re-specified in molluscs to create a plethora of body plans and nervous system organizations. Octopuses, having the largest brains of any invertebrate, independently evolved a learning circuit similar in organization and function to the mushroom body of insects and the hippocampus of mammals. In gastropods, homologous neurons have been re-specified for different functions. Even species exhibiting similar, possibly homologous behavior have fundamental differences in the connectivity of the neurons underlying that behavior. Thus, molluscan nervous systems provide clear examples of re-purposing of homologous genes and neurons for neural circuits.

  9. Large-Scale Simulations of Plastic Neural Networks on Neuromorphic Hardware

    PubMed Central

    Knight, James C.; Tully, Philip J.; Kaplan, Bernhard A.; Lansner, Anders; Furber, Steve B.

    2016-01-01

    SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 2.0 × 104 neurons and 5.1 × 107 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately 45× more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models. PMID:27092061

  10. Large-Scale Simulations of Plastic Neural Networks on Neuromorphic Hardware.

    PubMed

    Knight, James C; Tully, Philip J; Kaplan, Bernhard A; Lansner, Anders; Furber, Steve B

    2016-01-01

    SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 2.0 × 104 neurons and 5.1 × 107 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately 45× more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models.

  11. Injury- and Use-Related Plasticity in the Adult Auditory System.

    ERIC Educational Resources Information Center

    Irvine, Dexter R. F.

    2000-01-01

    This article discusses findings concerning the plasticity of auditory cortical processing mechanisms in adults, including the effects of restricted cochlear damage or behavioral training with acoustic stimuli on the frequency selectivity of auditory cortical neurons and evidence for analogous injury- and use-related plasticity in the adult human…

  12. Neuroticism and conscientiousness respectively constrain and facilitate short-term plasticity within the working memory neural network.

    PubMed

    Dima, Danai; Friston, Karl J; Stephan, Klaas E; Frangou, Sophia

    2015-10-01

    Individual differences in cognitive efficiency, particularly in relation to working memory (WM), have been associated both with personality dimensions that reflect enduring regularities in brain configuration, and with short-term neural plasticity, that reflects task-related changes in brain connectivity. To elucidate the relationship of these two divergent mechanisms, we tested the hypothesis that personality dimensions, which reflect enduring aspects of brain configuration, inform about the neurobiological framework within which short-term, task-related plasticity, as measured by effective connectivity, can be facilitated or constrained. As WM consistently engages the dorsolateral prefrontal (DLPFC), parietal (PAR), and anterior cingulate cortex (ACC), we specified a WM network model with bidirectional, ipsilateral, and contralateral connections between these regions from a functional magnetic resonance imaging dataset obtained from 40 healthy adults while performing the 3-back WM task. Task-related effective connectivity changes within this network were estimated using Dynamic Causal Modelling. Personality was evaluated along the major dimensions of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Only two dimensions were relevant to task-dependent effective connectivity. Neuroticism and Conscientiousness respectively constrained and facilitated neuroplastic responses within the WM network. These results suggest individual differences in cognitive efficiency arise from the interplay between enduring and short-term plasticity in brain configuration.

  13. Emergence of Slow Collective Oscillations in Neural Networks with Spike-Timing Dependent Plasticity

    NASA Astrophysics Data System (ADS)

    Mikkelsen, Kaare; Imparato, Alberto; Torcini, Alessandro

    2013-05-01

    The collective dynamics of excitatory pulse coupled neurons with spike-timing dependent plasticity is studied. The introduction of spike-timing dependent plasticity induces persistent irregular oscillations between strongly and weakly synchronized states, reminiscent of brain activity during slow-wave sleep. We explain the oscillations by a mechanism, the Sisyphus Effect, caused by a continuous feedback between the synaptic adjustments and the coherence in the neural firing. Due to this effect, the synaptic weights have oscillating equilibrium values, and this prevents the system from relaxing into a stationary macroscopic state.

  14. Neural ECM proteases in learning and synaptic plasticity.

    PubMed

    Tsilibary, Effie; Tzinia, Athina; Radenovic, Lidija; Stamenkovic, Vera; Lebitko, Tomasz; Mucha, Mariusz; Pawlak, Robert; Frischknecht, Renato; Kaczmarek, Leszek

    2014-01-01

    Recent studies implicate extracellular proteases in synaptic plasticity, learning, and memory. The data are especially strong for such serine proteases as thrombin, tissue plasminogen activator, neurotrypsin, and neuropsin as well as matrix metalloproteinases, MMP-9 in particular. The role of those enzymes in the aforementioned phenomena is supported by the experimental results on the expression patterns (at the gene expression and protein and enzymatic activity levels) and functional studies, including knockout mice, specific inhibitors, etc. Counterintuitively, the studies have shown that the extracellular proteolysis is not responsible mainly for an overall degradation of the extracellular matrix (ECM) and loosening perisynaptic structures, but rather allows for releasing signaling molecules from the ECM, transsynaptic proteins, and latent form of growth factors. Notably, there are also indications implying those enzymes in the major neuropsychiatric disorders, probably by contributing to synaptic aberrations underlying such diseases as schizophrenia, bipolar, autism spectrum disorders, and drug addiction.

  15. Cognitive and neural plasticity in older adults’ prospective memory following training with the Virtual Week computer game

    PubMed Central

    Rose, Nathan S.; Rendell, Peter G.; Hering, Alexandra; Kliegel, Matthias; Bidelman, Gavin M.; Craik, Fergus I. M.

    2015-01-01

    Prospective memory (PM) – the ability to remember and successfully execute our intentions and planned activities – is critical for functional independence and declines with age, yet few studies have attempted to train PM in older adults. We developed a PM training program using the Virtual Week computer game. Trained participants played the game in 12, 1-h sessions over 1 month. Measures of neuropsychological functions, lab-based PM, event-related potentials (ERPs) during performance on a lab-based PM task, instrumental activities of daily living, and real-world PM were assessed before and after training. Performance was compared to both no-contact and active (music training) control groups. PM on the Virtual Week game dramatically improved following training relative to controls, suggesting PM plasticity is preserved in older adults. Relative to control participants, training did not produce reliable transfer to laboratory-based tasks, but was associated with a reduction of an ERP component (sustained negativity over occipito-parietal cortex) associated with processing PM cues, indicative of more automatic PM retrieval. Most importantly, training produced far transfer to real-world outcomes including improvements in performance on real-world PM and activities of daily living. Real-world gains were not observed in either control group. Our findings demonstrate that short-term training with the Virtual Week game produces cognitive and neural plasticity that may result in real-world benefits to supporting functional independence in older adulthood. PMID:26578936

  16. Intraoperative mapping during repeat awake craniotomy reveals the functional plasticity of adult cortex.

    PubMed

    Southwell, Derek G; Hervey-Jumper, Shawn L; Perry, David W; Berger, Mitchel S

    2016-05-01

    negative for function. Overall, 6 (33.3%) of 18 patients exhibited loss of function at 1 or more motor or language sites between surgeries. Loss of function at these sites was not associated with neurological impairment at the time of repeat surgery, suggesting that neurological function was preserved through neural circuit reorganization or activation of latent functional pathways. CONCLUSIONS The adult central nervous system reorganizes motor and language areas in patients with glioma. Ultimately, adult neural plasticity may help to preserve motor and language function in the presence of evolving structural lesions. The insight gained from this subset of patients has implications for our understanding of brain plasticity in clinical settings.

  17. The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus.

    PubMed

    Li, Guangnan; Fang, Li; Fernández, Gloria; Pleasure, Samuel J

    2013-05-22

    Adult neurogenesis represents a unique form of plasticity in the dentate gyrus requiring the presence of long-lived neural stem cells (LL-NSCs). However, the embryonic origin of these LL-NSCs remains unclear. The prevailing model assumes that the dentate neuroepithelium throughout the longitudinal axis of the hippocampus generates both the LL-NSCs and embryonically produced granule neurons. Here we show that the NSCs initially originate from the ventral hippocampus during late gestation and then relocate into the dorsal hippocampus. The descendants of these cells are the source for the LL-NSCs in the subgranular zone (SGZ). Furthermore, we show that the origin of these cells and their maintenance in the dentate are controlled by distinct sources of Sonic Hedgehog (Shh). The revelation of the complexity of both the embryonic origin of hippocampal LL-NSCs and the sources of Shh has important implications for the functions of LL-NSCs in the adult hippocampus.

  18. Structural plasticity of interneurons in the adult brain: role of PSA-NCAM and implications for psychiatric disorders.

    PubMed

    Nacher, Juan; Guirado, Ramon; Castillo-Gómez, Esther

    2013-06-01

    Neuronal structural plasticity is known to have a major role in cognitive processes and in the response of the CNS to aversive experiences. This type of plasticity involves processes ranging from neurite outgrowth/retraction or dendritic spine remodeling, to the incorporation of new neurons to the established circuitry. However, the study of how these structural changes take place has been focused mainly on excitatory neurons, while little attention has been paid to interneurons. The exploration of these plastic phenomena in interneurons is very important, not only for our knowledge of CNS physiology, but also for understanding better the etiology of different psychiatric and neurological disorders in which alterations in the structure and connectivity of inhibitory networks have been described. Here we review recent work on the structural remodeling of interneurons in the adult brain, both in basal conditions and after chronic stress or sensory deprivation. We also describe studies from our laboratory and others on the putative mediators of this interneuronal structural plasticity, focusing on the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule is expressed by some interneurons in the adult CNS and, through its anti-adhesive and insulating properties, may participate in the remodeling of their structure. Finally, we review recent findings on the possible implication of PSA-NCAM on the remodeling of inhibitory neurons in certain psychiatric disorders and their treatments.

  19. Synchrony arising from a balanced synaptic plasticity in a network of heterogeneous neural oscillators

    NASA Astrophysics Data System (ADS)

    Karbowski, Jan; Ermentrout, G. Bard

    2002-03-01

    We investigate the dynamics of a recurrent network of coupled heterogeneous neural oscillators with experimentally observed spike-timing-dependent synaptic plasticity. We show both theoretically and by computer simulations that, in a regime of a balance between synaptic potentiation and depression, the network of such oscillators converges to a stable synchronous state. The stability of this state is fostered by flexible synaptic weights which adjust themselves based on the relative timing of firing of pre- and postsynaptic oscillators.

  20. Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit.

    PubMed

    Liu, Sha; Liu, Qili; Tabuchi, Masashi; Wu, Mark N

    2016-06-02

    Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca(2+) levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive.

  1. Modulation of synaptic plasticity by stress hormone associates with plastic alteration of synaptic NMDA receptor in the adult hippocampus.

    PubMed

    Tse, Yiu Chung; Bagot, Rosemary C; Hutter, Juliana A; Wong, Alice S; Wong, Tak Pan

    2011-01-01

    Stress exerts a profound impact on learning and memory, in part, through the actions of adrenal corticosterone (CORT) on synaptic plasticity, a cellular model of learning and memory. Increasing findings suggest that CORT exerts its impact on synaptic plasticity by altering the functional properties of glutamate receptors, which include changes in the motility and function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of glutamate receptor (AMPAR) that are responsible for the expression of synaptic plasticity. Here we provide evidence that CORT could also regulate synaptic plasticity by modulating the function of synaptic N-methyl-D-aspartate receptors (NMDARs), which mediate the induction of synaptic plasticity. We found that stress level CORT applied to adult rat hippocampal slices potentiated evoked NMDAR-mediated synaptic responses within 30 min. Surprisingly, following this fast-onset change, we observed a slow-onset (>1 hour after termination of CORT exposure) increase in synaptic expression of GluN2A-containing NMDARs. To investigate the consequences of the distinct fast- and slow-onset modulation of NMDARs for synaptic plasticity, we examined the formation of long-term potentiation (LTP) and long-term depression (LTD) within relevant time windows. Paralleling the increased NMDAR function, both LTP and LTD were facilitated during CORT treatment. However, 1-2 hours after CORT treatment when synaptic expression of GluN2A-containing NMDARs is increased, bidirectional plasticity was no longer facilitated. Our findings reveal the remarkable plasticity of NMDARs in the adult hippocampus in response to CORT. CORT-mediated slow-onset increase in GluN2A in hippocampal synapses could be a homeostatic mechanism to normalize synaptic plasticity following fast-onset stress-induced facilitation.

  2. Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity

    PubMed Central

    Ramírez-Barrantes, R.; Cordova, C.; Poblete, H.; Muñoz, P.; Marchant, I.; Wianny, F.; Olivero, P.

    2016-01-01

    The development of new strategies to renew and repair neuronal networks using neural plasticity induced by stem cell graft could enable new therapies to cure diseases that were considered lethal until now. In adequate microenvironment a neuronal progenitor must receive molecular signal of a specific cellular context to determine fate, differentiation, and location. TRPV1, a nonselective calcium channel, is expressed in neurogenic regions of the brain like the subgranular zone of the hippocampal dentate gyrus and the telencephalic subventricular zone, being valuable for neural differentiation and neural plasticity. Current data show that TRPV1 is involved in several neuronal functions as cytoskeleton dynamics, cell migration, survival, and regeneration of injured neurons, incorporating several stimuli in neurogenesis and network integration. The function of TRPV1 in the brain is under intensive investigation, due to multiple places where it has been detected and its sensitivity for different chemical and physical agonists, and a new role of TRPV1 in brain function is now emerging as a molecular tool for survival and control of neural stem cells. PMID:26881090

  3. Learning to Perceive Structure from Motion and Neural Plasticity in Patients with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Kim, Nam-Gyoon; Park, Jong-Hee

    2010-01-01

    Recent research has demonstrated that Alzheimer's disease (AD) affects the visual sensory pathways, producing a variety of visual deficits, including the capacity to perceive structure-from-motion (SFM). Because the sensory areas of the adult brain are known to retain a large degree of plasticity, the present study was conducted to explore whether…

  4. A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks

    PubMed Central

    Wang, Runchun M.; Hamilton, Tara J.; Tapson, Jonathan C.; van Schaik, André

    2015-01-01

    We present a neuromorphic implementation of multiple synaptic plasticity learning rules, which include both Spike Timing Dependent Plasticity (STDP) and Spike Timing Dependent Delay Plasticity (STDDP). We present a fully digital implementation as well as a mixed-signal implementation, both of which use a novel dynamic-assignment time-multiplexing approach and support up to 226 (64M) synaptic plasticity elements. Rather than implementing dedicated synapses for particular types of synaptic plasticity, we implemented a more generic synaptic plasticity adaptor array that is separate from the neurons in the neural network. Each adaptor performs synaptic plasticity according to the arrival times of the pre- and post-synaptic spikes assigned to it, and sends out a weighted or delayed pre-synaptic spike to the post-synaptic neuron in the neural network. This strategy provides great flexibility for building complex large-scale neural networks, as a neural network can be configured for multiple synaptic plasticity rules without changing its structure. We validate the proposed neuromorphic implementations with measurement results and illustrate that the circuits are capable of performing both STDP and STDDP. We argue that it is practical to scale the work presented here up to 236 (64G) synaptic adaptors on a current high-end FPGA platform. PMID:26041985

  5. A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks.

    PubMed

    Wang, Runchun M; Hamilton, Tara J; Tapson, Jonathan C; van Schaik, André

    2015-01-01

    We present a neuromorphic implementation of multiple synaptic plasticity learning rules, which include both Spike Timing Dependent Plasticity (STDP) and Spike Timing Dependent Delay Plasticity (STDDP). We present a fully digital implementation as well as a mixed-signal implementation, both of which use a novel dynamic-assignment time-multiplexing approach and support up to 2(26) (64M) synaptic plasticity elements. Rather than implementing dedicated synapses for particular types of synaptic plasticity, we implemented a more generic synaptic plasticity adaptor array that is separate from the neurons in the neural network. Each adaptor performs synaptic plasticity according to the arrival times of the pre- and post-synaptic spikes assigned to it, and sends out a weighted or delayed pre-synaptic spike to the post-synaptic neuron in the neural network. This strategy provides great flexibility for building complex large-scale neural networks, as a neural network can be configured for multiple synaptic plasticity rules without changing its structure. We validate the proposed neuromorphic implementations with measurement results and illustrate that the circuits are capable of performing both STDP and STDDP. We argue that it is practical to scale the work presented here up to 2(36) (64G) synaptic adaptors on a current high-end FPGA platform.

  6. Plasticity of Adult Human Pancreatic Duct Cells by Neurogenin3-Mediated Reprogramming

    PubMed Central

    Bonné, Stefan; Heremans, Yves; Borup, Rehannah; Van de Casteele, Mark; Ling, Zhidong; Pipeleers, Daniel; Ravassard, Philippe; Nielsen, Finn; Ferrer, Jorge; Heimberg, Harry

    2012-01-01

    Aims/Hypothesis Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. Methods The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. Results Ngn3 stimulates duct cells to express a focused set of genes that are characteristic for islet endocrine cells and/or neural tissues. This neuro-endocrine shift however, is incomplete with less than 10% of full duct-to-endocrine reprogramming achieved. Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. Conclusions/Interpretation The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes. PMID:22606327

  7. Thermotaxis of C. elegans as a model for temperature perception, neural information processing and neural plasticity.

    PubMed

    Kimata, Tsubasa; Sasakura, Hiroyuki; Ohnishi, Noriyuki; Nishio, Nana; Mori, Ikue

    2012-01-01

    Thermotaxis is a model to elucidate how nervous systems sense and memorize environmental conditions to regulate behavioral strategies in Caenorhabditis elegans. The genetic and neural imaging analyses revealed molecular and cellular bases of this experience-dependent behavior. Surprisingly, thermosensory neurons themselves memorize the sensed temperatures. Recently developed techniques for optical manipulation of neuronal activity have facilitated the revelation that there is a sophisticated information flow between sensory neurons and interneurons. Further studies on thermotaxis will allow us to understand the fundamental logics of neural processing from sensory perceptions to behavioral outputs.

  8. Thermotaxis of C. elegans as a model for temperature perception, neural information processing and neural plasticity

    PubMed Central

    Kimata, Tsubasa; Sasakura, Hiroyuki; Ohnishi, Noriyuki; Nishio, Nana; Mori, Ikue

    2012-01-01

    Thermotaxis is a model to elucidate how nervous systems sense and memorize environmental conditions to regulate behavioral strategies in Caenorhabditis elegans. The genetic and neural imaging analyses revealed molecular and cellular bases of this experience-dependent behavior. Surprisingly, thermosensory neurons themselves memorize the sensed temperatures. Recently developed techniques for optical manipulation of neuronal activity have facilitated the revelation that there is a sophisticated information flow between sensory neurons and interneurons. Further studies on thermotaxis will allow us to understand the fundamental logics of neural processing from sensory perceptions to behavioral outputs. PMID:24058821

  9. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot.

    PubMed

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin; Manoonpong, Poramate

    2015-01-01

    Walking animals, like insects, with little neural computing can effectively perform complex behaviors. For example, they can walk around their environment, escape from corners/deadlocks, and avoid or climb over obstacles. While performing all these behaviors, they can also adapt their movements to deal with an unknown situation. As a consequence, they successfully navigate through their complex environment. The versatile and adaptive abilities are the result of an integration of several ingredients embedded in their sensorimotor loop. Biological studies reveal that the ingredients include neural dynamics, plasticity, sensory feedback, and biomechanics. Generating such versatile and adaptive behaviors for a many degrees-of-freedom (DOFs) walking robot is a challenging task. Thus, in this study, we present a bio-inspired approach to solve this task. Specifically, the approach combines neural mechanisms with plasticity, exteroceptive sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent neural network consisting of two fully connected neurons. Online correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking robot. The turning information is transmitted as descending steering signals to the neural locomotion control which translates the signals into motor actions. As a result, the robot can walk around and adapt its turning angle for avoiding obstacles in different situations. The adaptation also enables the robot to effectively escape from sharp corners or deadlocks. Using backbone joint control embedded in the the locomotion control allows the robot to climb over small obstacles

  10. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot

    PubMed Central

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin; Manoonpong, Poramate

    2015-01-01

    Walking animals, like insects, with little neural computing can effectively perform complex behaviors. For example, they can walk around their environment, escape from corners/deadlocks, and avoid or climb over obstacles. While performing all these behaviors, they can also adapt their movements to deal with an unknown situation. As a consequence, they successfully navigate through their complex environment. The versatile and adaptive abilities are the result of an integration of several ingredients embedded in their sensorimotor loop. Biological studies reveal that the ingredients include neural dynamics, plasticity, sensory feedback, and biomechanics. Generating such versatile and adaptive behaviors for a many degrees-of-freedom (DOFs) walking robot is a challenging task. Thus, in this study, we present a bio-inspired approach to solve this task. Specifically, the approach combines neural mechanisms with plasticity, exteroceptive sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent neural network consisting of two fully connected neurons. Online correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking robot. The turning information is transmitted as descending steering signals to the neural locomotion control which translates the signals into motor actions. As a result, the robot can walk around and adapt its turning angle for avoiding obstacles in different situations. The adaptation also enables the robot to effectively escape from sharp corners or deadlocks. Using backbone joint control embedded in the the locomotion control allows the robot to climb over small obstacles

  11. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    PubMed Central

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  12. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies.

    PubMed

    Oliva, Carolina A; Vargas, Jessica Y; Inestrosa, Nibaldo C

    2013-12-03

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer's disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts.

  13. NMDA Receptors Mediate Stimulus-Timing-Dependent Plasticity and Neural Synchrony in the Dorsal Cochlear Nucleus

    PubMed Central

    Stefanescu, Roxana A.; Shore, Susan E.

    2015-01-01

    Auditory information relayed by auditory nerve fibers and somatosensory information relayed by granule cell parallel fibers converge on the fusiform cells (FCs) of the dorsal cochlear nucleus, the first brain station of the auditory pathway. In vitro, parallel fiber synapses on FCs exhibit spike-timing-dependent plasticity with Hebbian learning rules, partially mediated by the NMDA receptor (NMDAr). Well-timed bimodal auditory-somatosensory stimulation, in vivo equivalent of spike-timing-dependent plasticity, can induce stimulus-timing-dependent plasticity (StTDP) of the FCs spontaneous and tone-evoked firing rates. In healthy guinea pigs, the resulting distribution of StTDP learning rules across a FC neural population is dominated by a Hebbian profile while anti-Hebbian, suppressive and enhancing LRs are less frequent. In this study, we investigate in vivo, the NMDAr contribution to FC baseline activity and long term plasticity. We find that blocking the NMDAr decreases the synchronization of FC- spontaneous activity and mediates differential modulation of FC rate-level functions such that low, and high threshold units are more likely to increase, and decrease, respectively, their maximum amplitudes. Three significant alterations in mean learning-rule profiles were identified: transitions from an initial Hebbian profile towards (1) an anti-Hebbian; (2) a suppressive profile; and (3) transitions from an anti-Hebbian to a Hebbian profile. FC units preserving their learning rules showed instead, NMDAr-dependent plasticity to unimodal acoustic stimulation, with persistent depression of tone-evoked responses changing to persistent enhancement following the NMDAr antagonist. These results reveal a crucial role of the NMDAr in mediating FC baseline activity and long-term plasticity which have important implications for signal processing and auditory pathologies related to maladaptive plasticity of dorsal cochlear nucleus circuitry. PMID:26622224

  14. Enabling functional neural circuit simulations with distributed computing of neuromodulated plasticity.

    PubMed

    Potjans, Wiebke; Morrison, Abigail; Diesmann, Markus

    2010-01-01

    A major puzzle in the field of computational neuroscience is how to relate system-level learning in higher organisms to synaptic plasticity. Recently, plasticity rules depending not only on pre- and post-synaptic activity but also on a third, non-local neuromodulatory signal have emerged as key candidates to bridge the gap between the macroscopic and the microscopic level of learning. Crucial insights into this topic are expected to be gained from simulations of neural systems, as these allow the simultaneous study of the multiple spatial and temporal scales that are involved in the problem. In particular, synaptic plasticity can be studied during the whole learning process, i.e., on a time scale of minutes to hours and across multiple brain areas. Implementing neuromodulated plasticity in large-scale network simulations where the neuromodulatory signal is dynamically generated by the network itself is challenging, because the network structure is commonly defined purely by the connectivity graph without explicit reference to the embedding of the nodes in physical space. Furthermore, the simulation of networks with realistic connectivity entails the use of distributed computing. A neuromodulated synapse must therefore be informed in an efficient way about the neuromodulatory signal, which is typically generated by a population of neurons located on different machines than either the pre- or post-synaptic neuron. Here, we develop a general framework to solve the problem of implementing neuromodulated plasticity in a time-driven distributed simulation, without reference to a particular implementation language, neuromodulator, or neuromodulated plasticity mechanism. We implement our framework in the simulator NEST and demonstrate excellent scaling up to 1024 processors for simulations of a recurrent network incorporating neuromodulated spike-timing dependent plasticity.

  15. Potential of adult neural stem cells in stroke therapy.

    PubMed

    Andres, Robert H; Choi, Raymond; Steinberg, Gary K; Guzman, Raphael

    2008-11-01

    Despite state-of-the-art therapy, clinical outcome after stroke remains poor, with many patients left permanently disabled and dependent on care. Stem cell therapy has evolved as a promising new therapeutic avenue for the treatment of stroke in experimental studies, and recent clinical trials have proven its feasibility and safety in patients. Replacement of damaged cells and restoration of function can be accomplished by transplantation of different cell types, such as embryonic, fetal or adult stem cells, human fetal tissue and genetically engineered cell lines. Adult neural stem cells offer the advantage of avoiding the ethical problems associated with embryonic or fetal stem cells and can be harvested as autologous grafts from the individual patients. Furthermore, stimulation of endogenous adult stem cell-mediated repair mechanisms in the brain might offer new avenues for stroke therapy without the necessity of transplantation. However, important scientific issues need to be addressed to advance our understanding of the molecular mechanisms underlying the critical steps in cell-based repair to allow the introduction of these experimental techniques into clinical practice. This review describes up-to-date experimental concepts using adult neural stem cells for the treatment of stroke.

  16. Causal measures of structure and plasticity in simulated and living neural networks.

    PubMed

    Cadotte, Alex J; DeMarse, Thomas B; He, Ping; Ding, Mingzhou

    2008-10-07

    A major goal of neuroscience is to understand the relationship between neural structures and their function. Recording of neural activity with arrays of electrodes is a primary tool employed toward this goal. However, the relationships among the neural activity recorded by these arrays are often highly complex making it problematic to accurately quantify a network's structural information and then relate that structure to its function. Current statistical methods including cross correlation and coherence have achieved only modest success in characterizing the structural connectivity. Over the last decade an alternative technique known as Granger causality is emerging within neuroscience. This technique, borrowed from the field of economics, provides a strong mathematical foundation based on linear auto-regression to detect and quantify "causal" relationships among different time series. This paper presents a combination of three Granger based analytical methods that can quickly provide a relatively complete representation of the causal structure within a neural network. These are a simple pairwise Granger causality metric, a conditional metric, and a little known computationally inexpensive subtractive conditional method. Each causal metric is first described and evaluated in a series of biologically plausible neural simulations. We then demonstrate how Granger causality can detect and quantify changes in the strength of those relationships during plasticity using 60 channel spike train data from an in vitro cortical network measured on a microelectrode array. We show that these metrics can not only detect the presence of causal relationships, they also provide crucial information about the strength and direction of that relationship, particularly when that relationship maybe changing during plasticity. Although we focus on the analysis of multichannel spike train data the metrics we describe are applicable to any stationary time series in which causal

  17. Effects of cellular homeostatic intrinsic plasticity on dynamical and computational properties of biological recurrent neural networks.

    PubMed

    Naudé, Jérémie; Cessac, Bruno; Berry, Hugues; Delord, Bruno

    2013-09-18

    Homeostatic intrinsic plasticity (HIP) is a ubiquitous cellular mechanism regulating neuronal activity, cardinal for the proper functioning of nervous systems. In invertebrates, HIP is critical for orchestrating stereotyped activity patterns. The functional impact of HIP remains more obscure in vertebrate networks, where higher order cognitive processes rely on complex neural dynamics. The hypothesis has emerged that HIP might control the complexity of activity dynamics in recurrent networks, with important computational consequences. However, conflicting results about the causal relationships between cellular HIP, network dynamics, and computational performance have arisen from machine-learning studies. Here, we assess how cellular HIP effects translate into collective dynamics and computational properties in biological recurrent networks. We develop a realistic multiscale model including a generic HIP rule regulating the neuronal threshold with actual molecular signaling pathways kinetics, Dale's principle, sparse connectivity, synaptic balance, and Hebbian synaptic plasticity (SP). Dynamic mean-field analysis and simulations unravel that HIP sets a working point at which inputs are transduced by large derivative ranges of the transfer function. This cellular mechanism ensures increased network dynamics complexity, robust balance with SP at the edge of chaos, and improved input separability. Although critically dependent upon balanced excitatory and inhibitory drives, these effects display striking robustness to changes in network architecture, learning rates, and input features. Thus, the mechanism we unveil might represent a ubiquitous cellular basis for complex dynamics in neural networks. Understanding this robustness is an important challenge to unraveling principles underlying self-organization around criticality in biological recurrent neural networks.

  18. Stem cells and neural signalling: the case of neoblast recruitment and plasticity in low dose X-ray treated planarians.

    PubMed

    Rossi, Leonardo; Iacopetti, Paola; Salvetti, Alessandra

    2012-01-01

    Planarians (Platyhelminthes) possess an abundant population of adult stem cells, the neoblasts, capable to give rise to both somatic and germ cells. Although neoblasts share similar morphological features, several pieces of evidence suggest that they constitute a heterogeneous population of cells with distinct ultrastructural and molecular features. We found that in planarians treated with low X-ray doses (5 Gy), only a few neoblasts survive. Among these cells, those located close to the nervous system activate an intense proliferation program and migrate to reconstitute the whole complex neoblast population. This phenomenon is inhibited by the substance P receptor antagonist spantide, and accompanied by the up-regulation of a number of genes implicated in neuronal signalling and plasticity, suggesting that signals of neural origin modulate neoblast proliferation and/or migration. Here, we review these findings and the literature available on the influence of the nervous system on stem cell activity, both in planarians and vertebrates, and we propose 5 Gy-treated planarians as a unique model system to study the influence of neural signalling on stem cell biology.

  19. Adult attachment style modulates neural responses in a mentalizing task.

    PubMed

    Schneider-Hassloff, H; Straube, B; Nuscheler, B; Wemken, G; Kircher, T

    2015-09-10

    Adult attachment style (AAS) is a personality trait that affects social cognition. Behavioral data suggest that AAS influences mentalizing proficiency, i.e. the ability to predict and explain people's behavior with reference to mental states, but the neural correlates are unknown. We here tested how the AAS dimensions "avoidance" (AV) and "anxiety" (ANX) modulate neural correlates of mentalizing. We measured brain activation using functional magnetic resonance imaging (fMRI) in 164 healthy subjects during an interactive mentalizing paradigm (Prisoner's Dilemma Game). AAS was assessed with the Relationship Scales Questionnaire, including the subscales AV and ANX. Our task elicited a strong activation of the mentalizing network, including bilateral precuneus, (anterior, middle, and posterior) cingulate cortices, temporal poles, inferior frontal gyri (IFG), temporoparietal junctions, superior medial frontal gyri as well as right medial orbital frontal gyrus, superior temporal gyrus, middle frontal gyrus (MFG), and amygdala. We found that AV is positively and ANX negatively correlated with task-associated neural activity in the right amygdala, MFG, midcingulate cortex, and superior parietal lobule, and in bilateral IFG. These data suggest that avoidantly attached adults activate brain areas implicated in emotion regulation and cognitive control to a larger extent than anxiously attached individuals during mentalizing.

  20. Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia

    PubMed Central

    Crabtree, Gregg W.; Gogos, Joseph A.

    2014-01-01

    Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations. PMID:25505409

  1. Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia.

    PubMed

    Crabtree, Gregg W; Gogos, Joseph A

    2014-01-01

    Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations.

  2. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  3. Behavioral and magnetoencephalographic correlates of plasticity in the adult human brain

    PubMed Central

    Ramachandran, V. S.

    1993-01-01

    Recent behavioral and physiological evidence suggests that even brief sensory deprivation can lead to the rapid emergence of new and functionally effective neural connections in the adult human brain. Images Fig. 2 PMID:8248123

  4. Unsupervised discrimination of patterns in spiking neural networks with excitatory and inhibitory synaptic plasticity

    PubMed Central

    Srinivasa, Narayan; Cho, Youngkwan

    2014-01-01

    A spiking neural network model is described for learning to discriminate among spatial patterns in an unsupervised manner. The network anatomy consists of source neurons that are activated by external inputs, a reservoir that resembles a generic cortical layer with an excitatory-inhibitory (EI) network and a sink layer of neurons for readout. Synaptic plasticity in the form of STDP is imposed on all the excitatory and inhibitory synapses at all times. While long-term excitatory STDP enables sparse and efficient learning of the salient features in inputs, inhibitory STDP enables this learning to be stable by establishing a balance between excitatory and inhibitory currents at each neuron in the network. The synaptic weights between source and reservoir neurons form a basis set for the input patterns. The neural trajectories generated in the reservoir due to input stimulation and lateral connections between reservoir neurons can be readout by the sink layer neurons. This activity is used for adaptation of synapses between reservoir and sink layer neurons. A new measure called the discriminability index (DI) is introduced to compute if the network can discriminate between old patterns already presented in an initial training session. The DI is also used to compute if the network adapts to new patterns without losing its ability to discriminate among old patterns. The final outcome is that the network is able to correctly discriminate between all patterns—both old and new. This result holds as long as inhibitory synapses employ STDP to continuously enable current balance in the network. The results suggest a possible direction for future investigation into how spiking neural networks could address the stability-plasticity question despite having continuous synaptic plasticity. PMID:25566045

  5. Histone Deacetylase (HDAC) Inhibitors - Emerging Roles in Neuronal Memory, Learning, Synaptic Plasticity and Neural Regeneration

    PubMed Central

    Ahmad Ganai, Shabir; Ramadoss, Mahalakshmi; Mahadevan, Vijayalakshmi

    2016-01-01

    Epigenetic regulation of neuronal signalling through histone acetylation dictates transcription programs that govern neuronal memory, plasticity and learning paradigms. Histone Acetyl Transferases (HATs) and Histone Deacetylases (HDACs) are antagonistic enzymes that regulate gene expression through acetylation and deacetylation of histone proteins around which DNA is wrapped inside a eukaryotic cell nucleus. The epigenetic control of HDACs and the cellular imbalance between HATs and HDACs dictate disease states and have been implicated in muscular dystrophy, loss of memory, neurodegeneration and autistic disorders. Altering gene expression profiles through inhibition of HDACs is now emerging as a powerful technique in therapy. This review presents evolving applications of HDAC inhibitors as potential drugs in neurological research and therapy. Mechanisms that govern their expression profiles in neuronal signalling, plasticity and learning will be covered. Promising and exciting possibilities of HDAC inhibitors in memory formation, fear conditioning, ischemic stroke and neural regeneration have been detailed. PMID:26487502

  6. Neural mechanisms of short-term plasticity in the human visual system.

    PubMed

    Parks, Nathan A; Corballis, Paul M

    2012-12-01

    Following circumscribed retinal damage, extensive reorganization of topographically organized visual cortical areas has been demonstrated in several species of mammals (including humans). Although reorganization is often studied over extended time scales, neural response properties change within seconds of retinal deafferentation. Understanding the mechanisms underlying these short-term effects is essential for developing a complete picture of representational plasticity. One approach to the study of short-term plasticity has been to use an artificial scotoma, a stimulus-induced analog of a retinal scotoma, as a model. Here, we use event-related potentials in an artificial scotoma paradigm to examine 2 aspects of short-term plasticity in the human visual system. First, we investigated the changes within visual representations temporarily deprived of patterned visual input by probing the inner boundaries of an artificial scotoma. We found an enhanced early sensory P1, consistent with a reduction in inhibition (disinhibition), a proposed mechanism of short-term visual plasticity. Second, we investigated mechanisms through which representations of surrounding space invade a visually deprived area by probing the outer boundaries of an artificial scotoma. In this case, a later visual component, the N1, was enhanced, suggesting that feedback may provide a source of unmasked, or invading, activity to visually deprived representations.

  7. Axonal control of the adult neural stem cell niche.

    PubMed

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D; Tecott, Laurence H; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-04-03

    The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain's neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C.

  8. Live Imaging of Adult Neural Stem Cells in Rodents

    PubMed Central

    Ortega, Felipe; Costa, Marcos R.

    2016-01-01

    The generation of cells of the neural lineage within the brain is not restricted to early development. New neurons, oligodendrocytes, and astrocytes are produced in the adult brain throughout the entire murine life. However, despite the extensive research performed in the field of adult neurogenesis during the past years, fundamental questions regarding the cell biology of adult neural stem cells (aNSCs) remain to be uncovered. For instance, it is crucial to elucidate whether a single aNSC is capable of differentiating into all three different macroglial cell types in vivo or these distinct progenies constitute entirely separate lineages. Similarly, the cell cycle length, the time and mode of division (symmetric vs. asymmetric) that these cells undergo within their lineage progression are interesting questions under current investigation. In this sense, live imaging constitutes a valuable ally in the search of reliable answers to the previous questions. In spite of the current limitations of technology new approaches are being developed and outstanding amount of knowledge is being piled up providing interesting insights in the behavior of aNSCs. Here, we will review the state of the art of live imaging as well as the alternative models that currently offer new answers to critical questions. PMID:27013941

  9. Axonal Control of the Adult Neural Stem Cell Niche

    PubMed Central

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  10. Synchronization and long-time memory in neural networks with inhibitory hubs and synaptic plasticity

    NASA Astrophysics Data System (ADS)

    Bertolotti, Elena; Burioni, Raffaella; di Volo, Matteo; Vezzani, Alessandro

    2017-01-01

    We investigate the dynamical role of inhibitory and highly connected nodes (hub) in synchronization and input processing of leaky-integrate-and-fire neural networks with short term synaptic plasticity. We take advantage of a heterogeneous mean-field approximation to encode the role of network structure and we tune the fraction of inhibitory neurons fI and their connectivity level to investigate the cooperation between hub features and inhibition. We show that, depending on fI, highly connected inhibitory nodes strongly drive the synchronization properties of the overall network through dynamical transitions from synchronous to asynchronous regimes. Furthermore, a metastable regime with long memory of external inputs emerges for a specific fraction of hub inhibitory neurons, underlining the role of inhibition and connectivity also for input processing in neural networks.

  11. Learning, neural plasticity and sensitive periods: implications for language acquisition, music training and transfer across the lifespan.

    PubMed

    White, Erin J; Hutka, Stefanie A; Williams, Lynne J; Moreno, Sylvain

    2013-11-20

    Sensitive periods in human development have often been proposed to explain age-related differences in the attainment of a number of skills, such as a second language (L2) and musical expertise. It is difficult to reconcile the negative consequence this traditional view entails for learning after a sensitive period with our current understanding of the brain's ability for experience-dependent plasticity across the lifespan. What is needed is a better understanding of the mechanisms underlying auditory learning and plasticity at different points in development. Drawing on research in language development and music training, this review examines not only what we learn and when we learn it, but also how learning occurs at different ages. First, we discuss differences in the mechanism of learning and plasticity during and after a sensitive period by examining how language exposure versus training forms language-specific phonetic representations in infants and adult L2 learners, respectively. Second, we examine the impact of musical training that begins at different ages on behavioral and neural indices of auditory and motor processing as well as sensorimotor integration. Third, we examine the extent to which childhood training in one auditory domain can enhance processing in another domain via the transfer of learning between shared neuro-cognitive systems. Specifically, we review evidence for a potential bi-directional transfer of skills between music and language by examining how speaking a tonal language may enhance music processing and, conversely, how early music training can enhance language processing. We conclude with a discussion of the role of attention in auditory learning for learning during and after sensitive periods and outline avenues of future research.

  12. Learning, neural plasticity and sensitive periods: implications for language acquisition, music training and transfer across the lifespan

    PubMed Central

    White, Erin J.; Hutka, Stefanie A.; Williams, Lynne J.; Moreno, Sylvain

    2013-01-01

    Sensitive periods in human development have often been proposed to explain age-related differences in the attainment of a number of skills, such as a second language (L2) and musical expertise. It is difficult to reconcile the negative consequence this traditional view entails for learning after a sensitive period with our current understanding of the brain’s ability for experience-dependent plasticity across the lifespan. What is needed is a better understanding of the mechanisms underlying auditory learning and plasticity at different points in development. Drawing on research in language development and music training, this review examines not only what we learn and when we learn it, but also how learning occurs at different ages. First, we discuss differences in the mechanism of learning and plasticity during and after a sensitive period by examining how language exposure versus training forms language-specific phonetic representations in infants and adult L2 learners, respectively. Second, we examine the impact of musical training that begins at different ages on behavioral and neural indices of auditory and motor processing as well as sensorimotor integration. Third, we examine the extent to which childhood training in one auditory domain can enhance processing in another domain via the transfer of learning between shared neuro-cognitive systems. Specifically, we review evidence for a potential bi-directional transfer of skills between music and language by examining how speaking a tonal language may enhance music processing and, conversely, how early music training can enhance language processing. We conclude with a discussion of the role of attention in auditory learning for learning during and after sensitive periods and outline avenues of future research. PMID:24312022

  13. Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity

    PubMed Central

    Doboszewska, Urszula; Wlaź, Piotr; Nowak, Gabriel; Radziwoń-Zaleska, Maria

    2017-01-01

    Preclinical and clinical studies have demonstrated that zinc possesses antidepressant properties and that it may augment the therapy with conventional, that is, monoamine-based, antidepressants. In this review we aim to discuss the role of zinc in the pathophysiology and treatment of depression with regard to the monoamine hypothesis of the disease. Particular attention will be paid to the recently described zinc-sensing GPR39 receptor as well as aspects of zinc deficiency. Furthermore, an attempt will be made to give a possible explanation of the mechanisms by which zinc interacts with the monoamine system in the context of depression and neural plasticity. PMID:28299207

  14. Neural Plasticity in Functional and Anatomical MRI Studies of Children with Tourette Syndrome

    PubMed Central

    Eichele, Heike; Plessen, Kerstin J.

    2013-01-01

    Background: Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by chronic motor and vocal tics. The typical clinical course of an attenuation of symptoms during adolescence in parallel with the emerging self-regulatory control during development suggests that plastic processes may play an important role in the development of tic symptoms. Methods: We conducted a systematic search to identify existing imaging studies (both anatomical and functional magnetic resonance imaging [fMRI]) in young persons under the age of 19 years with TS. Results: The final search resulted in 13 original studies, which were reviewed with a focus on findings suggesting adaptive processes (using fMRI) and plasticity (using anatomical MRI). Differences in brain activation compared to healthy controls during tasks that require overriding of prepotent responses help to understand compensatory pathways in children with TS. Along with alterations in regions putatively representing the origin of tics, deviations in several other regions most likely represent an activity-dependent neural plasticity that help to modulate tic severity, such as the prefrontal cortex, but also in the corpus callosum and the limbic system. Discussion: Factors that potentially influence the development of adaptive changes in the brain of children with TS are age, comorbidity with other developmental disorders, medication use, IQ along with study-design or MRI techniques for acquisition, and analysis of data. The most prominent limitation of all studies is their cross-sectional design. Longitudinal studies extending to younger age groups and to children at risk for developing TS hopefully will confirm findings of neural plasticity in future investigations. PMID:23187150

  15. Different propagation speeds of recalled sequences in plastic spiking neural networks

    NASA Astrophysics Data System (ADS)

    Huang, Xuhui; Zheng, Zhigang; Hu, Gang; Wu, Si; Rasch, Malte J.

    2015-03-01

    Neural networks can generate spatiotemporal patterns of spike activity. Sequential activity learning and retrieval have been observed in many brain areas, and e.g. is crucial for coding of episodic memory in the hippocampus or generating temporal patterns during song production in birds. In a recent study, a sequential activity pattern was directly entrained onto the neural activity of the primary visual cortex (V1) of rats and subsequently successfully recalled by a local and transient trigger. It was observed that the speed of activity propagation in coordinates of the retinotopically organized neural tissue was constant during retrieval regardless how the speed of light stimulation sweeping across the visual field during training was varied. It is well known that spike-timing dependent plasticity (STDP) is a potential mechanism for embedding temporal sequences into neural network activity. How training and retrieval speeds relate to each other and how network and learning parameters influence retrieval speeds, however, is not well described. We here theoretically analyze sequential activity learning and retrieval in a recurrent neural network with realistic synaptic short-term dynamics and STDP. Testing multiple STDP rules, we confirm that sequence learning can be achieved by STDP. However, we found that a multiplicative nearest-neighbor (NN) weight update rule generated weight distributions and recall activities that best matched the experiments in V1. Using network simulations and mean-field analysis, we further investigated the learning mechanisms and the influence of network parameters on recall speeds. Our analysis suggests that a multiplicative STDP rule with dominant NN spike interaction might be implemented in V1 since recall speed was almost constant in an NMDA-dominant regime. Interestingly, in an AMPA-dominant regime, neural circuits might exhibit recall speeds that instead follow the change in stimulus speeds. This prediction could be tested in

  16. Plasticity and tuning by visual feedback of the stability of a neural integrator

    PubMed Central

    Major, Guy; Baker, Robert; Aksay, Emre; Mensh, Brett; Seung, H. Sebastian; Tank, David W.

    2004-01-01

    Persistent neural firing is of fundamental importance to working memory and other brain functions because it allows information to be held “online” following an input and to be integrated over time. Many models of persistent activity rely on some kind of positive feedback internal to the neural circuit concerned; however, too much feedback causes runaway firing (instability), and too little results in loss of persistence (leak). This parameter sensitivity leads to the hypothesis that the brain uses an error signal (external feedback) to tune the stability of persistent firing by adjusting the amount of internal feedback. We test this hypothesis by manipulating external visual feedback, a putative sensory error signal, in a model system for persistent firing, the goldfish oculomotor neural integrator. Over tens of minutes to hours, electronically controlled visual feedback consistent with a leaky or unstable integrator can drive the integrator progressively more unstable or leaky, respectively. Eye fixation time constants can be reduced >100-fold to <1 s. Normal visual feedback gradually retunes the integrator back to stability. Changes in the phase of the sinusoidal vestibulo-ocular response are consistent with integrator detuning, as are changes in ocular drift following eye position shifts compensating for brief passive head movements during fixations. Corresponding changes in persistent firing of integrator neurons are presented in the accompanying article. The presence, strength, and reversibility of the plasticity demonstrate that, in this system, external visual feedback plays a vital role in gradually tuning the stability of the neural integrator. PMID:15136746

  17. Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats

    PubMed Central

    Li, Xiao-Li; Yuan, Yong-Gui; Xu, Hua; Wu, Di; Gong, Wei-Gang; Geng, Lei-Yu; Wu, Fang-Fang; Tang, Hao; Xu, Lin

    2015-01-01

    Background: Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. Methods: Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray’s Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats’ depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. Results: The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. Conclusion: These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats’ depressive behaviors, suggesting a therapeutic target for further exploration. PMID:25899067

  18. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats*

    PubMed Central

    Tang, Qing-ping; Shen, Qin; Wu, Li-xiang; Feng, Xiang-ling; Liu, Hui; Wu, Bei; Huang, Xiao-song; Wang, Gai-qing; Li, Zhong-hao; Liu, Zun-jing

    2016-01-01

    Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes. PMID:27381726

  19. Removing brakes on adult brain plasticity: from molecular to behavioral interventions

    PubMed Central

    Bavelier, D.; Levi, D.M.; Li, R.W.; Dan, Y.; Hensch, T.K.

    2010-01-01

    Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as peri-neuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects. PMID:21068299

  20. Brain imaging of language plasticity in adopted adults: can a second language replace the first?

    PubMed

    Pallier, C; Dehaene, S; Poline, J-B; LeBihan, D; Argenti, A-M; Dupoux, E; Mehler, J

    2003-02-01

    Do the neural circuits that subserve language acquisition lose plasticity as they become tuned to the maternal language? We tested adult subjects born in Korea and adopted by French families in childhood; they have become fluent in their second language and report no conscious recollection of their native language. In behavioral tests assessing their memory for Korean, we found that they do not perform better than a control group of native French subjects who have never been exposed to Korean. We also used event-related functional magnetic resonance imaging to monitor cortical activations while the Korean adoptees and native French listened to sentences spoken in Korean, French and other, unknown, foreign languages. The adopted subjects did not show any specific activations to Korean stimuli relative to unknown languages. The areas activated more by French stimuli than by foreign stimuli were similar in the Korean adoptees and in the French native subjects, but with relatively larger extents of activation in the latter group. We discuss these data in light of the critical period hypothesis for language acquisition.

  1. Sleep and synaptic plasticity in the developing and adult brain.

    PubMed

    Frank, Marcos G

    2015-01-01

    Sleep is hypothesized to play an integral role in brain plasticity. This has traditionally been investigated using behavioral assays. In the last 10-15 years, studies combining sleep measurements with in vitro and in vivo models of synaptic plasticity have provided exciting new insights into how sleep alters synaptic strength. In addition, new theories have been proposed that integrate older ideas about sleep function and recent discoveries in the field of synaptic plasticity. There remain, however, important challenges and unanswered questions. For example, sleep does not appear to have a single effect on synaptic strength. An unbiased review of the literature indicates that the effects of sleep vary widely depending on ontogenetic stage, the type of waking experience (or stimulation protocols) that precede sleep and the type of neuronal synapse under examination. In this review, I discuss these key findings in the context of current theories that posit different roles for sleep in synaptic plasticity.

  2. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    PubMed Central

    Carvalho, Bettina; Hamerschmidt, Rogerio; Wiemes, Gislaine

    2014-01-01

    Introduction Neural response telemetry (NRT) is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI) users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC), that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts) and REC as a function of three parameters: A (saturation level, in microvolts), t0 (absolute refractory period, in seconds), and tau (curve of the model function), measured in three electrodes (apical, medial, and basal). Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode. PMID:25992145

  3. Field Patterns of Leaf Plasticity in Adults of the Long-lived Evergreen Quercus coccifera

    PubMed Central

    Rubio De Casas, Rafael; Vargas, Pablo; Pérez-Corona, Esther; Manrique, Esteban; Quintana, José Ramón; García-Verdugo, Carlos; Balaguer, Luis

    2007-01-01

    Background and Aims Quercus coccifera, as a long-lived sprouter, responds plastically to environmental variation. In this study, the role of foliar plasticity as a mechanism of habitat selection and modification within the canopy and across contrasted habitats was characterized. An examination was made of the differential contribution of inner and outer canopy layers to the crown plasticity expressed in the field by adult individuals and its dependence on environmental and genetic factors. Methods Within-crown variation in eight foliar traits was examined in nine populations dominated by Q. coccifera. The difference between mean trait values at the inner and outer canopy layers was used as a proxy for crown plasticity to light. Correlations between geographic distances, environmental differences (climatic and edaphic) and phenotypic divergence (means and plasticities) were assessed by partial Mantel tests. A subset of field measurements was compared with data from a previous common garden experiment. Key Results Phenotypic adjustment of sun leaves contributed significantly to the field variation in crown plasticity. Plasticity in leaf angle, lobation, xanthophyll cycle pigments and β-carotene content was expressed in sun and shade leaves concurrently and in opposite directions. Phenotypic plasticity was more strongly correlated with environmental variation than mean trait values. Populations of taller plants with larger, thinner (higher specific leaf area) and less spiny leaves exhibited greater plasticity. In these populations, the midday light environment was more uniform at the inner than at the outer canopy layers. Field and common garden data ranked populations in the same order of plasticity. Conclusions The expression of leaf plasticity resulted in a phenotypic differentiation that suggests a mechanism of habitat selection through division of labour across canopy layers. Signs of plasticity-mediated habitat modification were found only in the most plastic

  4. Neural injury alters proliferation and integration of adult-generated neurons in the dentate gyrus

    PubMed Central

    Perederiy, Julia V.; Luikart, Bryan W.; Washburn, Eric K.; Schnell, Eric; Westbrook, Gary L.

    2013-01-01

    Neural plasticity following brain injury illustrates the potential for regeneration in the central nervous system. Lesioning of the perforant path, which innervates the outer 2/3rds of the molecular layer of the dentate gyrus, was one of the first models to demonstrate structural plasticity of mature granule cells (Parnavelas, 1974; Caceres and Steward, 1983; Diekmann et al., 1996). The dentate gyrus also harbors a continuously proliferating population of neuronal precursors that can integrate into functional circuits and show enhanced short-term plasticity (Schmidt-Hieber et al., 2004; Abrous et al., 2005). To examine the response of adult-generated granule cells to unilateral complete transection of the perforant path in vivo, we tracked these cells using transgenic POMC-EGFP mice or by retroviral expression of GFP. Lesioning triggered a marked proliferation of newborn neurons. Subsequently, the dendrites of newborn neurons showed reduced complexity within the denervated zone, but dendritic spines still formed in the absence of glutamatergic nerve terminals. Electron micrographs confirmed the lack of intact presynaptic terminals apposing spines on mature cells and on newborn neurons. Newborn neurons, but not mature granule cells, had a higher density of dendritic spines in the inner molecular layer post-lesion, accompanied by an increase in miniature EPSC amplitudes and rise times. Our results indicate that injury causes an increase in newborn neurons and lamina-specific synaptic reorganization, indicative of enhanced plasticity. The presence of de novo dendritic spines in the denervated zone suggests that the post-lesion environment provides the necessary signals for spine formation. PMID:23486947

  5. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

    PubMed

    Ramos-Moreno, Tania; Galazo, Maria J; Porrero, Cesar; Martínez-Cerdeño, Verónica; Clascá, Francisco

    2006-01-01

    Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.

  6. Neural correlates of autobiographical memory retrieval in children and adults.

    PubMed

    Bauer, Patricia J; Pathman, Thanujeni; Inman, Cory; Campanella, Carolina; Hamann, Stephan

    2017-04-01

    Autobiographical memory (AM) is a critically important form of memory for life events that undergoes substantial developmental changes from childhood to adulthood. Relatively little is known regarding the functional neural correlates of AM retrieval in children as assessed with fMRI, and how they may differ from adults. We investigated this question with 14 children ages 8-11 years and 14 adults ages 19-30 years, contrasting AM retrieval with semantic memory (SM) retrieval. During scanning, participants were cued by verbal prompts to retrieve previously selected recent AMs or to verify semantic properties of words. As predicted, both groups showed AM retrieval-related increased activation in regions implicated in prior studies, including bilateral hippocampus, and prefrontal, posterior cingulate, and parietal cortices. Adults showed greater activation in the hippocampal/parahippocampal region as well as prefrontal and parietal cortex, relative to children; age-related differences were most prominent in the first 8 sec versus the second 8 sec of AM retrieval and when AM retrieval was contrasted with semantic retrieval. This study is the first to characterise similarities and differences during AM retrieval in children and adults using fMRI.

  7. Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

    PubMed Central

    Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Alvaro; Castro, Elena; dos Anjos, Severiano; Pascual-Brazo, Jesús; Linge, Raquel; Vargas, Veronica; Blanco, Helena; Martínez-Villayandre, Beatriz; Pazos, Ángel; Valdizán, Elsa M.

    2013-01-01

    It is widely accepted that changes underlying depression and antidepressant-like effects involve not only alterations in the levels of neurotransmitters as monoamines and their receptors in the brain, but also structural and functional changes far beyond. During the last two decades, emerging theories are providing new explanations about the neurobiology of depression and the mechanism of action of antidepressant strategies based on cellular changes at the CNS level. The neurotrophic/plasticity hypothesis of depression, proposed more than a decade ago, is now supported by multiple basic and clinical studies focused on the role of intracellular-signalling cascades that govern neural proliferation and plasticity. Herein, we review the state-of-the-art of the changes in these signalling pathways which appear to underlie both depressive disorders and antidepressant actions. We will especially focus on the hippocampal cellularity and plasticity modulation by serotonin, trophic factors as brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) through intracellular signalling pathways—cAMP, Wnt/β-catenin, and mTOR. Connecting the classic monoaminergic hypothesis with proliferation/neuroplasticity-related evidence is an appealing and comprehensive attempt for improving our knowledge about the neurobiological events leading to depression and associated to antidepressant therapies. PMID:23862076

  8. α-Tocopherol and Hippocampal Neural Plasticity in Physiological and Pathological Conditions

    PubMed Central

    Ambrogini, Patrizia; Betti, Michele; Galati, Claudia; Di Palma, Michael; Lattanzi, Davide; Savelli, David; Galli, Francesco; Cuppini, Riccardo; Minelli, Andrea

    2016-01-01

    Neuroplasticity is an “umbrella term” referring to the complex, multifaceted physiological processes that mediate the ongoing structural and functional modifications occurring, at various time- and size-scales, in the ever-changing immature and adult brain, and that represent the basis for fundamental neurocognitive behavioral functions; in addition, maladaptive neuroplasticity plays a role in the pathophysiology of neuropsychiatric dysfunctions. Experiential cues and several endogenous and exogenous factors can regulate neuroplasticity; among these, vitamin E, and in particular α-tocopherol (α-T), the isoform with highest bioactivity, exerts potent effects on many plasticity-related events in both the physiological and pathological brain. In this review, the role of vitamin E/α-T in regulating diverse aspects of neuroplasticity is analyzed and discussed, focusing on the hippocampus, a brain structure that remains highly plastic throughout the lifespan and is involved in cognitive functions. Vitamin E-mediated influences on hippocampal synaptic plasticity and related cognitive behavior, on post-natal development and adult hippocampal neurogenesis, as well as on cellular and molecular disruptions in kainate-induced temporal seizures are described. Besides underscoring the relevance of its antioxidant properties, non-antioxidant functions of vitamin E/α-T, mainly involving regulation of cell signaling molecules and their target proteins, have been highlighted to help interpret the possible mechanisms underlying the effects on neuroplasticity. PMID:27983697

  9. Plasticity and tuning of the time course of analog persistent firing in a neural integrator

    PubMed Central

    Major, Guy; Baker, Robert; Aksay, Emre; Seung, H. Sebastian; Tank, David W.

    2004-01-01

    In a companion paper, we reported that the goldfish oculomotor neural integrator could be trained to instability or leak by rotating the visual surround with a velocity proportional to +/- horizontal eye position, respectively. Here we analyze changes in the firing rate behavior of neurons in area I in the caudal brainstem, a central component of the oculomotor neural integrator. Persistent firing could be detuned to instability and leak, respectively, along with fixation behavior. Prolonged training could reduce the time constant of persistent firing of some cells by more than an order of magnitude, to <1 s. Normal visual feedback gradually retuned persistent firing of integrator neurons toward stability, along with fixation behavior. In animals with unstable fixations, approximately half of the eye position-related cells had upward or unstable firing rate drift. In animals with leaky fixations, two-thirds of the eye position-related cells showed leaky firing drift. The remaining eye position-related cells, generally those with lower eye position thresholds, showed a more complex pattern of history-dependent/predictive firing rate drift in relation to eye drift. These complex drift cells often showed a drop in maximum persistent firing rate after training to leak. Despite this diversity, firing drift and the degree of instability or leak in firing rates were broadly correlated with fixation performance. The presence, strength, and reversibility of this plasticity demonstrate that, in this system, visual feedback plays a vital role in gradually tuning the time course of persistent neural firing. PMID:15136747

  10. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    PubMed

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  11. Ischemic long-term-potentiation (iLTP): perspectives to set the threshold of neural plasticity toward therapy

    PubMed Central

    Lenz, Maximilian; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    The precise role of neural plasticity under pathological conditions remains not well understood. It appears to be well accepted, however, that changes in the ability of neurons to express plasticity accompany neurological diseases. Here, we discuss recent experimental evidence, which suggests that synaptic plasticity induced by a pathological stimulus, i.e., ischemic long-term-potentiation (iLTP) of excitatory synapses, could play an important role for post-stroke recovery by influencing the post-lesional reorganization of surviving neuronal networks. PMID:26692832

  12. Comparative aspects of adult neural stem cell activity in vertebrates.

    PubMed

    Grandel, Heiner; Brand, Michael

    2013-03-01

    At birth or after hatching from the egg, vertebrate brains still contain neural stem cells which reside in specialized niches. In some cases, these stem cells are deployed for further postnatal development of parts of the brain until the final structure is reached. In other cases, postnatal neurogenesis continues as constitutive neurogenesis into adulthood leading to a net increase of the number of neurons with age. Yet, in other cases, stem cells fuel neuronal turnover. An example is protracted development of the cerebellar granular layer in mammals and birds, where neurogenesis continues for a few weeks postnatally until the granular layer has reached its definitive size and stem cells are used up. Cerebellar growth also provides an example of continued neurogenesis during adulthood in teleosts. Again, it is the granular layer that grows as neurogenesis continues and no definite adult cerebellar size is reached. Neuronal turnover is most clearly seen in the telencephalon of male canaries, where projection neurons are replaced in nucleus high vocal centre each year before the start of a new mating season--circuitry reconstruction to achieve changes of the song repertoire in these birds? In this review, we describe these and other examples of adult neurogenesis in different vertebrate taxa. We also compare the structure of the stem cell niches to find common themes in their organization despite different functions adult neurogenesis serves in different species. Finally, we report on regeneration of the zebrafish telencephalon after injury to highlight similarities and differences of constitutive neurogenesis and neuronal regeneration.

  13. MECP2 regulates cortical plasticity underlying a learned behaviour in adult female mice

    PubMed Central

    Krishnan, Keerthi; Lau, Billy Y. B.; Ewall, Gabrielle; Huang, Z. Josh; Shea, Stephen D.

    2017-01-01

    Neurodevelopmental disorders are marked by inappropriate synaptic connectivity early in life, but how disruption of experience-dependent plasticity contributes to cognitive and behavioural decline in adulthood is unclear. Here we show that pup gathering behaviour and associated auditory cortical plasticity are impaired in female Mecp2het mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2het females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2het through genetic or pharmacological manipulations targeting the GABAergic network restored gathering behaviour. We propose that pup gathering learning triggers a transient epoch of inhibitory plasticity in auditory cortex that is dysregulated in Mecp2het. In this window of heightened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently from their effects on early development. PMID:28098153

  14. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons.

    PubMed

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A

    2014-10-17

    During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia-NCAMs) modulate cell-cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia-NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb's to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell-cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  15. Sisyphus effect in pulse-coupled excitatory neural networks with spike-timing-dependent plasticity

    NASA Astrophysics Data System (ADS)

    Mikkelsen, Kaare; Imparato, Alberto; Torcini, Alessandro

    2014-06-01

    The collective dynamics of excitatory pulse-coupled neural networks with spike-timing-dependent plasticity (STDP) is studied. Depending on the model parameters stationary states characterized by high or low synchronization can be observed. In particular, at the transition between these two regimes, persistent irregular low frequency oscillations between strongly and weakly synchronized states are observable, which can be identified as infraslow oscillations with frequencies ≃0.02-0.03 Hz. Their emergence can be explained in terms of the Sisyphus effect, a mechanism caused by a continuous feedback between the evolution of the coherent population activity and of the average synaptic weight. Due to this effect, the synaptic weights have oscillating equilibrium values, which prevents the neuronal population from relaxing into a stationary macroscopic state.

  16. Perinatal selective serotonin reuptake inhibitor exposure: impact on brain development and neural plasticity.

    PubMed

    Pawluski, Jodi L

    2012-01-01

    Selective serotonin reuptake inhibitor (SSRI) medications are the most common antidepressant treatment used during pregnancy and the postpartum period. Up to 10% of pregnant women are prescribed SSRIs. Serotonin plays an integral part in neurodevelopment, and questions have been raised about the placental transfer of SSRIs and the effects of preventing reuptake of presynaptic serotonin on fetal neurodevelopment. Preclinical data is beginning to document a role of early exposure to SSRIs in long-term developmental outcomes related to a number of brain regions, such as the hippocampus, cortex and cerebellum. To date, the majority of preclinical work has investigated the developmental effects of SSRIs in the offspring of healthy mothers; however, more research is needed on the effects of these medications in the face of maternal adversity. This minireview will highlight emerging evidence from clinical and preclinical studies investigating the impact of perinatal SSRI exposure on brain development and neural plasticity.

  17. Vulnerability of the neural circuitry underlying sexual behavior to chronic adult exposure to oral bisphenol a in male mice.

    PubMed

    Picot, Marie; Naulé, Lydie; Marie-Luce, Clarisse; Martini, Mariangela; Raskin, Kalina; Grange-Messent, Valérie; Franceschini, Isabelle; Keller, Matthieu; Mhaouty-Kodja, Sakina

    2014-02-01

    There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

  18. DNA methyltransferase activity is required for memory-related neural plasticity in the lateral amygdala.

    PubMed

    Maddox, Stephanie A; Watts, Casey S; Schafe, Glenn E

    2014-01-01

    We have previously shown that auditory Pavlovian fear conditioning is associated with an increase in DNA methyltransferase (DNMT) expression in the lateral amygdala (LA) and that intra-LA infusion or bath application of an inhibitor of DNMT activity impairs the consolidation of an auditory fear memory and long-term potentiation (LTP) at thalamic and cortical inputs to the LA, in vitro. In the present study, we use awake behaving neurophysiological techniques to examine the role of DNMT activity in memory-related neurophysiological changes accompanying fear memory consolidation and reconsolidation in the LA, in vivo. We show that auditory fear conditioning results in a training-related enhancement in the amplitude of short-latency auditory-evoked field potentials (AEFPs) in the LA. Intra-LA infusion of a DNMT inhibitor impairs both fear memory consolidation and, in parallel, the consolidation of training-related neural plasticity in the LA; that is, short-term memory (STM) and short-term training-related increases in AEFP amplitude in the LA are intact, while long-term memory (LTM) and long-term retention of training-related increases in AEFP amplitudes are impaired. In separate experiments, we show that intra-LA infusion of a DNMT inhibitor following retrieval of an auditory fear memory has no effect on post-retrieval STM or short-term retention of training-related changes in AEFP amplitude in the LA, but significantly impairs both post-retrieval LTM and long-term retention of AEFP amplitude changes in the LA. These findings are the first to demonstrate the necessity of DNMT activity in the consolidation and reconsolidation of memory-associated neural plasticity, in vivo.

  19. Corticomotor excitability and plasticity following complex visuomotor training in young and old adults.

    PubMed

    Cirillo, John; Todd, Gabrielle; Semmler, John G

    2011-12-01

    Previous studies with transcranial magnetic stimulation (TMS) have shown that advancing age may influence plasticity induction in human motor cortex (M1), but these changes have been assessed with TMS-induced paradigms or simple motor tasks. The aim of this study was to examine changes in corticospinal excitability and intracortical inhibition as markers of corticomotor plasticity following complex motor training in young and old adults. Electromyographic recordings were obtained from the right first dorsal interosseous (FDI) muscle of 16 young (20-35 years) and 16 older (aged 60-75 years) adults before and after motor skill training. Motor training consisted of three 6-minute blocks of a complex visuomotor task that required matching the metacarpophalangeal (MCP) joint angle of the index finger using abduction-adduction movements. Single- and paired-pulse TMS over the left M1 was used to assess changes in right FDI motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before and after each training block. Visuomotor tracking performance was diminished in old compared with young adults throughout training. However, improvement in tracking error was similar for young and old adults (7-24% increase in each training block). For young and old adults, motor training increased FDI MEP amplitude (≥ 20%) and reduced the magnitude of SICI (≥ 19%) after each visuomotor training block, reflecting use-dependent plasticity. However, no difference in corticomotor plasticity (change in MEP or SICI) was observed between young and old adults. Further studies are needed to identify the experimental or behavioral factors that might contribute to the maintenance of corticomotor plasticity in older adults.

  20. In vivo reactive neural plasticity investigation by means of correlative two photon: electron microscopy

    NASA Astrophysics Data System (ADS)

    Allegra Mascaro, A. L.; Cesare, P.; Sacconi, L.; Grasselli, G.; Mandolesi, G.; Maco, B.; Knott, G.; Huang, L.; De Paola, V.; Strata, P.; Pavone, F. S.

    2013-02-01

    In the adult nervous system, different populations of neurons correspond to different regenerative behavior. Although previous works showed that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury1, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of singularly axotomized climbing fibers (CF) to investigate their reparative properties in the adult central nervous system (CNS) in vivo. Time lapse two-photon imaging has been combined to laser nanosurgery2, 3 to define a temporal pattern of the degenerative event and to follow the structural rearrangement after injury. To characterize the damage and to elucidate the possible formation of new synaptic contacts on the sprouted branches of the lesioned CF, we combined two-photon in vivo imaging with block face scanning electron microscopy (FIB-SEM). Here we describe the approach followed to characterize the reactive plasticity after injury.

  1. Voluntary physical exercise promotes ocular dominance plasticity in adult mouse primary visual cortex.

    PubMed

    Kalogeraki, Evgenia; Greifzu, Franziska; Haack, Franziska; Löwel, Siegrid

    2014-11-12

    Ocular dominance (OD) plasticity in the mouse primary visual cortex (V1) declines during aging and is absent beyond postnatal day (P) 110 when mice are raised in standard cages (SCs; Lehmann and Löwel, 2008). In contrast, raising mice in an enriched environment (EE) preserved a juvenile-like OD plasticity into late adulthood (Greifzu et al., 2014). EE raising provides the mice with more social interactions, voluntary physical exercise, and cognitive stimulation compared with SC, raising the question whether all components are needed or whether one of them is already sufficient to prolong plasticity. To test whether voluntary physical exercise alone already prolongs the sensitive phase for OD plasticity, we raised mice from 7 d before birth to adulthood in slightly larger than normal SCs with or without a running wheel (RW). When the mice were older than P135, we visualized V1 activity before and after monocular deprivation (MD) using intrinsic signal optical imaging. Adult RW-raised mice continued to show an OD shift toward the open eye after 7 d of MD, while age-matched SC mice without a RW did not show OD plasticity. Notably, running just during the 7 d MD period restored OD plasticity in adult SC-raised mice. In addition, the OD shift of the RW mice was mediated by a decrease of deprived-eye responses in V1, a signature of "juvenile-like" plasticity. We conclude that voluntary physical exercise alone is sufficient to promote plasticity in adult mouse V1.

  2. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    SciTech Connect

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  3. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    SciTech Connect

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A.

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  4. Trigeminothalamic barrelette neurons: natural structural side asymmetries and sensory input-dependent plasticity in adult rats.

    PubMed

    Negredo, P; Martin, Y B; Lagares, A; Castro, J; Villacorta, J A; Avendaño, C

    2009-11-10

    In the rodent trigeminal principal nucleus (Pr5) the barrelette thalamic-projecting neurons relay information from individual whiskers to corresponding contralateral thalamic barreloids. Here we investigated the presence of lateral asymmetries in the dendritic trees of these neurons, and the morphometric changes resulting from input-dependent plasticity in young adult rats. After retrograde labeling with dextran amines from the thalamus, neurons were digitally reconstructed with Neurolucida, and metrically and topologically analyzed with NeuroExplorer. The most unexpected and remarkable result was the observation of side-to-side asymmetries in the barrelette neurons of control rats. These asymmetries more significantly involved the number of low-grade trees and the total dendritic length, which were greater on the left side. Chronic global input loss resulting from infraorbital nerve (IoN) transection, or loss of active touch resulting from whisker clipping in the right neutralized, or even reversed, the observed lateral differences. While results after IoN transection have to be interpreted in the context of partial neuron death in this model, profound bilateral changes were found after haptic loss, which is achieved without inflicting any nerve damage. After whisker trimming, neurons on the left side closely resembled neurons on the right in controls, the natural dendritic length asymmetry being reversed mainly by a shortening of the left trees and a more moderate elongation of the right trees. These results demonstrate that dendritic morphometry is both side- and input-dependent, and that unilateral manipulation of the sensory periphery leads to bilateral morphometric changes in second order neurons of the whisker-barrel system. The presence of anatomical asymmetries in neural structures involved in early stages of somatosensory processing could help explain the expression of sensory input-dependent behavioral asymmetries.

  5. Chronic pain resolution after a lucid dream: a case for neural plasticity?

    PubMed

    Zappaterra, Mauro; Jim, Lysander; Pangarkar, Sanjog

    2014-03-01

    Chronic pain is often managed using a multidisciplinary, biopsychosocial approach. Interventions targeting the biological, psychological, and social aspects of both the patient and the pain have been demonstrated to provide objective and subjective improvement in chronic pain symptoms. The mechanism by which pain attenuation occurs after these interventions remains to be elucidated. While there is a relatively large body of empirical literature suggesting that functional and structural changes in the peripheral and central nervous systems are key in the development and maintenance of chronic pain states, less is known about changes that take place in the nervous system as a whole after biopsychosocial interventions. Using as a model the unique case of Mr. S, a patient suffering with chronic pain for 22 years who experienced a complete resolution of pain after a lucid dream following 2 years of biopsychosocial treatments, we postulate that central nervous system (CNS) reorganization (i.e., neural plasticity) serves as a possible mechanism for the therapeutic benefit of multidisciplinary treatments, and may set a neural framework for healing, in this case via a lucid dream.

  6. A novel analytical characterization for short-term plasticity parameters in spiking neural networks.

    PubMed

    O'Brien, Michael J; Thibeault, Corey M; Srinivasa, Narayan

    2014-01-01

    Short-term plasticity (STP) is a phenomenon that widely occurs in the neocortex with implications for learning and memory. Based on a widely used STP model, we develop an analytical characterization of the STP parameter space to determine the nature of each synapse (facilitating, depressing, or both) in a spiking neural network based on presynaptic firing rate and the corresponding STP parameters. We demonstrate consistency with previous work by leveraging the power of our characterization to replicate the functional volumes that are integral for the previous network stabilization results. We then use our characterization to predict the precise transitional point from the facilitating regime to the depressing regime in a simulated synapse, suggesting in vitro experiments to verify the underlying STP model. We conclude the work by integrating our characterization into a framework for finding suitable STP parameters for self-sustaining random, asynchronous activity in a prescribed recurrent spiking neural network. The systematic process resulting from our analytical characterization improves the success rate of finding the requisite parameters for such networks by three orders of magnitude over a random search.

  7. Triphasic spike-timing-dependent plasticity organizes networks to produce robust sequences of neural activity

    PubMed Central

    Waddington, Amelia; Appleby, Peter A.; De Kamps, Marc; Cohen, Netta

    2012-01-01

    Synfire chains have long been proposed to generate precisely timed sequences of neural activity. Such activity has been linked to numerous neural functions including sensory encoding, cognitive and motor responses. In particular, it has been argued that synfire chains underlie the precise spatiotemporal firing patterns that control song production in a variety of songbirds. Previous studies have suggested that the development of synfire chains requires either initial sparse connectivity or strong topological constraints, in addition to any synaptic learning rules. Here, we show that this necessity can be removed by using a previously reported but hitherto unconsidered spike-timing-dependent plasticity (STDP) rule and activity-dependent excitability. Under this rule the network develops stable synfire chains that possess a non-trivial, scalable multi-layer structure, in which relative layer sizes appear to follow a universal function. Using computational modeling and a coarse grained random walk model, we demonstrate the role of the STDP rule in growing, molding and stabilizing the chain, and link model parameters to the resulting structure. PMID:23162457

  8. Adherent neural stem (NS) cells from fetal and adult forebrain.

    PubMed

    Pollard, Steven M; Conti, Luciano; Sun, Yirui; Goffredo, Donato; Smith, Austin

    2006-07-01

    Stable in vitro propagation of central nervous system (CNS) stem cells would offer expanded opportunities to dissect basic molecular, cellular, and developmental processes and to model neurodegenerative disease. CNS stem cells could also provide a source of material for drug discovery assays and cell replacement therapies. We have recently reported the generation of adherent, symmetrically expandable, neural stem (NS) cell lines derived both from mouse and human embryonic stem cells and from fetal forebrain (Conti L, Pollard SM, Gorba T, Reitano E, Toselli M, Biella G, Sun Y, Sanzone S, Ying QL, Cattaneo E, Smith A. 2005. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol 3(9):e283). These NS cells retain neuronal and glial differentiation potential after prolonged passaging and are transplantable. NS cells are likely to comprise the resident stem cell population within heterogeneous neurosphere cultures. Here we demonstrate that similar NS cell cultures can be established from the adult mouse brain. We also characterize the growth factor requirements for NS cell derivation and self-renewal. We discuss our current understanding of the relationship of NS cell lines to physiological progenitor cells of fetal and adult CNS.

  9. S100B overexpression increases behavioral and neural plasticity in response to the social environment during adolescence.

    PubMed

    Buschert, Jens; Hohoff, Christa; Touma, Chadi; Palme, Rupert; Rothermundt, Matthias; Arolt, Volker; Zhang, Weiqi; Ambrée, Oliver

    2013-11-01

    Genetic variants as well as increased serum levels of the neurotrophic factor S100B are associated with different psychiatric disorders. However, elevated S100B levels are also related to a better therapeutic outcome in psychiatric patients. The functional role of elevated S100B in psychiatric disorders is still unclear. Hence, this study was designed in order to elucidate the differential effects of S100B overexpression in interaction with chronic social stress during adolescence on emotional behavior and adult neurogenesis. S100B transgenic and wild-type mice were housed either in socially stable or unstable environments during adolescence, between postnatal days 28 and 77. In adulthood, anxiety-related behavior in the open field, dark-light, and novelty-induced suppression of feeding test as well as survival of proliferating hippocampal progenitor cells were assessed. S100B transgenic mice revealed significantly reduced anxiety-related behavior in the open field compared to wild-types when reared in stable social conditions. In contrast, when transgenic mice grew up in unstable social conditions, their level of anxiety-related behavior was comparable to the levels of wild-type mice. In addition, S100B overexpressing mice from unstable housing conditions displayed higher numbers of surviving newborn cells in the adult hippocampus which developed into mature neurons. In conclusion, elevated S100B levels increase the susceptibility to environmental stimuli during adolescence resulting in more variable behavioral and neural phenotypes in adulthood. In humans, this increased plasticity might lead to both, enhanced risk for psychiatric disorders in negative environments and improved therapeutic outcome in positive environments.

  10. Kv3.1 channels stimulate adult neural precursor cell proliferation and neuronal differentiation.

    PubMed

    Yasuda, Takahiro; Cuny, Hartmut; Adams, David J

    2013-05-15

    Adult neural stem/precursor cells (NPCs) play a pivotal role in neuronal plasticity throughout life. Among ion channels identified in adult NPCs, voltage-gated delayed rectifier K(+) (KDR) channels are dominantly expressed. However, the KDR channel subtype and its physiological role are still undefined. We used real-time quantitative RT-PCR and gene knockdown techniques to identify a major functional KDR channel subtype in adult NPCs. Dominant mRNA expression of Kv3.1, a high voltage-gated KDR channel, was quantitatively confirmed. Kv3.1 gene knockdown with specific small interfering RNAs (siRNA) for Kv3.1 significantly inhibited Kv3.1 mRNA expression by 63.9% (P < 0.001) and KDR channel currents by 52.2% (P < 0.001). This indicates that Kv3.1 is the subtype responsible for producing KDR channel outward currents. Resting membrane properties, such as resting membrane potential, of NPCs were not affected by Kv3.1 expression. Kv3.1 knockdown with 300 nm siRNA inhibited NPC growth (increase in cell numbers) by 52.9% (P < 0.01). This inhibition was attributed to decreased cell proliferation, not increased cell apoptosis. We also established a convenient in vitro imaging assay system to evaluate NPC differentiation using NPCs from doublecortin-green fluorescent protein transgenic mice. Kv3.1 knockdown also significantly reduced neuronal differentiation by 31.4% (P < 0.01). We have demonstrated that Kv3.1 is a dominant functional KDR channel subtype expressed in adult NPCs and plays key roles in NPC proliferation and neuronal lineage commitment during differentiation.

  11. Cognitive-affective neural plasticity following active-controlled mindfulness intervention

    PubMed Central

    Allen, Micah; Dietz, Martin; Blair, Karina S.; van Beek, Martijn; Rees, Geraint; Vestergaard-Poulsen, Peter; Lutz, Antoine; Roepstorff, Andreas

    2015-01-01

    Mindfulness meditation is a set of attention-based, regulatory and self-inquiry training regimes. Although the impact of mindfulness meditation training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act on attention through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures has made it difficult to distinguish the role of these mechanisms. To resolve this question we conducted a fully randomized 6-week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active control group. We measured behavioral metacognition and whole-brain Blood Oxygenation Level Dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex (DLPFC) responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group by time interactions on negative affect-related RTs or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response-inhibition and increased recruitment of dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), and right anterior insula during negative valence processing. Collectively our findings highlight the importance of active control in MT research, and indicate unique neural mechanisms for progressive stages of mindfulness training. PMID:23115195

  12. Cognitive-affective neural plasticity following active-controlled mindfulness intervention.

    PubMed

    Allen, Micah; Dietz, Martin; Blair, Karina S; van Beek, Martijn; Rees, Geraint; Vestergaard-Poulsen, Peter; Lutz, Antoine; Roepstorff, Andreas

    2012-10-31

    Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry training regimes. Although the impact of mindfulness training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles. To resolve this question we conducted a fully randomized 6 week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active-control group. We measured behavioral metacognition and whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative valence processing. Our findings highlight the importance of active control in MT research, indicate unique neural mechanisms for progressive stages of mindfulness training, and suggest that optimal application of MT may differ depending on context, contrary to a one-size-fits-all approach.

  13. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  14. Social experience modulates ocular dominance plasticity differentially in adult male and female mice.

    PubMed

    Balog, Jenny; Matthies, Ulrike; Naumann, Lisa; Voget, Mareike; Winter, Christine; Lehmann, Konrad

    2014-12-01

    Environmental factors have long been known to regulate brain plasticity. We investigated the potential influence of social experience on ocular dominance plasticity. Fully adult female or male mice were monocularly deprived for four days and kept a) either alone or in pairs of the same sex and b) either in a small cage or a large, featureless arena. While mice kept alone did not show ocular dominance plasticity, no matter whether in a cage or in an arena, paired female mice in both environmental conditions displayed a shift of ocular dominance towards the open eye. Paired male mice, in contrast, showed no plasticity in the cage, but a very strong ocular dominance shift in the arena. This effect was not due to increased locomotion, since the covered distance was similar in single and paired male mice in the arena, and furnishing cages with a running wheel did not enable ocular dominance plasticity in cage-housed mice. Confirming recent results in rats, the plasticity-enhancing effect of the social environment was shown to be mediated by serotonin. Our results demonstrate that social experience has a strong effect on cortical plasticity that is sex-dependent. This has potential consequences both for animal research and for human education and rehabilitation.

  15. Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults

    PubMed Central

    Young-Bernier, Marielle; Tanguay, Annick N.; Davidson, Patrick S. R.; Tremblay, François

    2014-01-01

    Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application. Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS. PMID:25147523

  16. Altered neuronal architecture and plasticity in the visual cortex of adult MMP-3-deficient mice.

    PubMed

    Aerts, Jeroen; Nys, Julie; Moons, Lieve; Hu, Tjing-Tjing; Arckens, Lutgarde

    2015-09-01

    Matrix metalloproteinases (MMPs) are Zn(2+)-dependent endopeptidases considered to be essential for normal brain development and neuroplasticity by modulating extracellular matrix proteins, receptors, adhesion molecules, growth factors and cytoskeletal proteins. Specifically, MMP-3 has recently been implicated in synaptic plasticity, hippocampus-dependent learning and neuronal development and migration in the cerebellum. However, the function(s) of this enzyme in the neocortex is understudied. Therefore, we explored the phenotypical characteristics of the neuronal architecture and the capacity for experience-dependent cortical plasticity in the visual cortex of adult MMP-3-deficient (MMP-3(-/-)) mice. Golgi-Cox stainings revealed a significant reduction in apical dendritic length and an increased number of apical obliques for layer V pyramidal neurons in the visual cortex of adult MMP-3(-/-) mice compared to wild-type (WT) animals. In addition, a significant upregulation of both phosphorylated and non-phosphorylated neurofilament protein (NF)-high, phosphorylated NF-medium, NF-low and α-internexin was detected in the visual cortex of MMP-3(-/-) mice. To assess the effect of MMP-3 deficiency on cortical plasticity, we monocularly enucleated adult MMP-3(-/-) mice and analyzed the reactivation of the contralateral visual cortex 7 weeks post-enucleation. In contrast to previous results in C57Bl/6J adult mice, activity remained confined to the binocular zone and did not expand into the monocular regions indicative for an aberrant open-eye potentiation. Permanent hypoactivity in the monocular cortex lateral and medial to V1 also indicated a lack of cross-modal plasticity. These observations demonstrate that genetic inactivation of MMP-3 has profound effects on the structural integrity and plasticity response of the visual cortex of adult mice.

  17. A Behavioral Treatment for Traumatic Brain Injury-Associated Visual Dysfunction Based on Adult Cortical Plasticity

    DTIC Science & Technology

    2012-10-01

    amblyopic adults (Polat, 2008, Polat, Ma‐ Naim , Belkin & Sagi, 2004). We were  the first to show plasticity in adults with a visual deficit that was...Ma‐ Naim , T., Belkin, M., & Sagi, D. (2004). Improving vision in adult amblyopia by  perceptual learning. Proc Natl Acad Sci U S A, 101 (17), 6692

  18. A Behavioral Treatment for Traumatic Brain Injury-associated Visual Dysfunction Based on Adult Cortical Plasticity

    DTIC Science & Technology

    2011-10-01

    in amblyopic adults (Polat, 2008, Polat, Ma‐ Naim , Belkin & Sagi, 2004). We were  the first to show plasticity in adults with a visual deficit that...visual functions. Vision Res,   13    Polat, U., Ma‐ Naim , T., Belkin, M., & Sagi, D. (2004). Improving vision in adult amblyopia by  perceptual learning

  19. Is sleep essential for neural plasticity in humans, and how does it affect motor and cognitive recovery?

    PubMed

    Gorgoni, Maurizio; D'Atri, Aurora; Lauri, Giulia; Rossini, Paolo Maria; Ferlazzo, Fabio; De Gennaro, Luigi

    2013-01-01

    There is a general consensus that sleep is strictly linked to memory, learning, and, in general, to the mechanisms of neural plasticity, and that this link may directly affect recovery processes. In fact, a coherent pattern of empirical findings points to beneficial effect of sleep on learning and plastic processes, and changes in synaptic plasticity during wakefulness induce coherent modifications in EEG slow wave cortical topography during subsequent sleep. However, the specific nature of the relation between sleep and synaptic plasticity is not clear yet. We reported findings in line with two models conflicting with respect to the underlying mechanisms, that is, the "synaptic homeostasis hypothesis" and the "consolidation" hypothesis, and some recent results that may reconcile them. Independently from the specific mechanisms involved, sleep loss is associated with detrimental effects on plastic processes at a molecular and electrophysiological level. Finally, we reviewed growing evidence supporting the notion that plasticity-dependent recovery could be improved managing sleep quality, while monitoring EEG during sleep may help to explain how specific rehabilitative paradigms work. We conclude that a better understanding of the sleep-plasticity link could be crucial from a rehabilitative point of view.

  20. Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity

    PubMed Central

    Bonzano, Sara; Bovetti, Serena; Gendusa, Claudio; Peretto, Paolo; De Marchis, Silvia

    2016-01-01

    The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID:27199651

  1. Neural correlates of executive attention in adults born very preterm

    PubMed Central

    Daamen, Marcel; Bäuml, Josef G.; Scheef, Lukas; Meng, Chun; Jurcoane, Alina; Jaekel, Julia; Sorg, Christian; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra; Boecker, Henning

    2015-01-01

    Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing. PMID:26640769

  2. Contrasting roles for parvalbumin-expressing inhibitory neurons in two forms of adult visual cortical plasticity

    PubMed Central

    Kaplan, Eitan S; Cooke, Sam F; Komorowski, Robert W; Chubykin, Alexander A; Thomazeau, Aurore; Khibnik, Lena A; Gavornik, Jeffrey P; Bear, Mark F

    2016-01-01

    The roles played by cortical inhibitory neurons in experience-dependent plasticity are not well understood. Here we evaluate the participation of parvalbumin-expressing (PV+) GABAergic neurons in two forms of experience-dependent modification of primary visual cortex (V1) in adult mice: ocular dominance (OD) plasticity resulting from monocular deprivation and stimulus-selective response potentiation (SRP) resulting from enriched visual experience. These two forms of plasticity are triggered by different events but lead to a similar increase in visual cortical response. Both also require the NMDA class of glutamate receptor (NMDAR). However, we find that PV+ inhibitory neurons in V1 play a critical role in the expression of SRP and its behavioral correlate of familiarity recognition, but not in the expression of OD plasticity. Furthermore, NMDARs expressed within PV+ cells, reversibly inhibited by the psychotomimetic drug ketamine, play a critical role in SRP, but not in the induction or expression of adult OD plasticity. DOI: http://dx.doi.org/10.7554/eLife.11450.001 PMID:26943618

  3. BRAIN REGENERATION IN PHYSIOLOGY AND PATHOLOGY: THE IMMUNE SIGNATURE DRIVING THERAPEUTIC PLASTICITY OF NEURAL STEM CELLS

    PubMed Central

    Martino, Gianvito; Pluchino, Stefano; Bonfanti, Luca; Schwartz, Michal

    2013-01-01

    Regenerative processes occurring under physiological (maintenance) and pathological (reparative) conditions are a fundamental part of life and vary greatly among different species, individuals, and tissues. Physiological regeneration occurs naturally as a consequence of normal cell erosion, or as an inevitable outcome of any biological process aiming at the restoration of homeostasis. Reparative regeneration occurs as a consequence of tissue damage. Although the central nervous system (CNS) has been considered for years as a “perennial” tissue, it has recently become clear that both physiological and reparative regeneration occur also within the CNS to sustain tissue homeostasis and repair. Proliferation and differentiation of neural stem/progenitor cells (NPCs) residing within the healthy CNS, or surviving injury, are considered crucial in sustaining these processes. Thus a large number of experimental stem cell-based transplantation systems for CNS repair have recently been established. The results suggest that transplanted NPCs promote tissue repair not only via cell replacement but also through their local contribution to changes in the diseased tissue milieu. This review focuses on the remarkable plasticity of endogenous and exogenous (transplanted) NPCs in promoting repair. Special attention will be given to the cross-talk existing between NPCs and CNS-resident microglia as well as CNS-infiltrating immune cells from the circulation, as a crucial event sustaining NPC-mediated neuroprotection. Finally, we will propose the concept of the context-dependent potency of transplanted NPCs (therapeutic plasticity) to exert multiple therapeutic actions, such as cell replacement, neurotrophic support, and immunomodulation, in CNS repair. PMID:22013212

  4. All About Running: Synaptic Plasticity, Growth Factors and Adult Hippocampal Neurogenesis

    PubMed Central

    Vivar, Carmen; Potter, Michelle C.; van Praag, Henriette

    2015-01-01

    Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF). PMID:22847651

  5. Behavioral and neural plasticity caused by early social experiences: the case of the honeybee

    PubMed Central

    Arenas, Andrés; Ramírez, Gabriela P.; Balbuena, María Sol; Farina, Walter M.

    2013-01-01

    Cognitive experiences during the early stages of life play an important role in shaping future behavior. Behavioral and neural long-term changes after early sensory and associative experiences have been recently reported in the honeybee. This invertebrate is an excellent model for assessing the role of precocious experiences on later behavior due to its extraordinarily tuned division of labor based on age polyethism. These studies are mainly focused on the role and importance of experiences occurred during the first days of the adult lifespan, their impact on foraging decisions, and their contribution to coordinate food gathering. Odor-rewarded experiences during the first days of honeybee adulthood alter the responsiveness to sucrose, making young hive bees more sensitive to assess gustatory features about the nectar brought back to the hive and affecting the dynamic of the food transfers and the propagation of food-related information within the colony. Early olfactory experiences lead to stable and long-term associative memories that can be successfully recalled after many days, even at foraging ages. Also they improve memorizing of new associative learning events later in life. The establishment of early memories promotes stable reorganization of the olfactory circuits inducing structural and functional changes in the antennal lobe (AL). Early rewarded experiences have relevant consequences at the social level too, biasing dance and trophallaxis partner choice and affecting recruitment. Here, we revised recent results in bees' physiology, behavior, and sociobiology to depict how the early experiences affect their cognition abilities and neural-related circuits. PMID:23986708

  6. Behavioral and neural plasticity caused by early social experiences: the case of the honeybee.

    PubMed

    Arenas, Andrés; Ramírez, Gabriela P; Balbuena, María Sol; Farina, Walter M

    2013-01-01

    Cognitive experiences during the early stages of life play an important role in shaping future behavior. Behavioral and neural long-term changes after early sensory and associative experiences have been recently reported in the honeybee. This invertebrate is an excellent model for assessing the role of precocious experiences on later behavior due to its extraordinarily tuned division of labor based on age polyethism. These studies are mainly focused on the role and importance of experiences occurred during the first days of the adult lifespan, their impact on foraging decisions, and their contribution to coordinate food gathering. Odor-rewarded experiences during the first days of honeybee adulthood alter the responsiveness to sucrose, making young hive bees more sensitive to assess gustatory features about the nectar brought back to the hive and affecting the dynamic of the food transfers and the propagation of food-related information within the colony. Early olfactory experiences lead to stable and long-term associative memories that can be successfully recalled after many days, even at foraging ages. Also they improve memorizing of new associative learning events later in life. The establishment of early memories promotes stable reorganization of the olfactory circuits inducing structural and functional changes in the antennal lobe (AL). Early rewarded experiences have relevant consequences at the social level too, biasing dance and trophallaxis partner choice and affecting recruitment. Here, we revised recent results in bees' physiology, behavior, and sociobiology to depict how the early experiences affect their cognition abilities and neural-related circuits.

  7. The first juvenile specimens of Plateosaurus engelhardti from Frick, Switzerland: isolated neural arches and their implications for developmental plasticity in a basal sauropodomorph

    PubMed Central

    Sander, P. Martin

    2014-01-01

    The dinosaur Plateosaurus engelhardti is the most abundant dinosaur in the Late Triassic of Europe and the best known basal sauropodomorph. Plateosaurus engelhardti was one of the first sauropodomorph dinosaurs to display a large body size. Remains can be found in the Norian stage of the Late Triassic in over 40 localities in Central Europe (France, Germany, and Switzerland) and in Greenland. Since the first discovery of P. engelhardti no juvenile specimens of this species had been described in detail. Here we describe the first remains of juvenile individuals, isolated cervical and dorsal neural arches from Switzerland. These were separated postmortem from their respective centra because of unfused neurocentral sutures. However the specimens share the same neural arch morphology found in adults. Morphometric analysis suggests body lengths of the juvenile individuals that is greater than those of most adult specimens. This supports the hypothesis of developmental plasticity in Plateosaurus engelhardti that previously had been based on histological data only. Alternative hypotheses for explaining the poor correlation between ontogenetic stage and size in this taxon are multiple species or sexual morphs with little morphological variance or time-averaging of individuals from populations differing in body size. PMID:25071987

  8. Spred-2 expression is associated with neural repair of injured adult zebrafish brain.

    PubMed

    Lim, Fei Tieng; Ogawa, Satoshi; Parhar, Ishwar S

    2016-11-01

    Sprouty-related protein-2 (Spred-2) is a negative regulator of extracellular signal-regulated kinases (ERK) pathway, which is important for cell proliferation, neuronal differentiation, plasticity and survival. Nevertheless, its general molecular characteristics such as gene expression patterns and potential role in neural repair in the brain remain unknown. Thus, this study aimed to characterise the expression of spred-2 in the zebrafish brain. Digoxigenin-in situ hybridization showed spred-2 mRNA-expressing cells were mainly seen in the proliferative zones such as the olfactory bulb, telencephalon, optic tectum, cerebellum, and the dorsal and ventral hypothalamus, and most of which were neuronal cells. To evaluate the potential role of spred-2 in neuro-regeneration, spred-2 gene expression was examined in the dorsal telencephalon followed by mechanical-lesion. Real-time PCR showed a significant reduction of spred-2 mRNA levels in the telencephalon on 1-day till 2-days post-lesion and gradually increased to normal levels as compared with intact. Furthermore, to confirm involvement of Spred-2 signalling in the cell proliferation after brain injury, double-labelling of spred-2 in-situ hybridization with immunofluorescence of BrdU and phosphorylated-ERK1/2 (p-ERK1/2), a downstream of Spred-2 was performed. Increase of BrdU and p-ERK1/2 immunoreactive cells suggest that a decrease in spred-2 after injury might associated with activation of the ERK pathway to stimulate cell proliferation in the adult zebrafish brain. The present study demonstrates the possible role of Spred-2 signalling in cell proliferative phase during the neural repair in the injured zebrafish brain.

  9. Hemispheric differences in use-dependent corticomotor plasticity in young and old adults.

    PubMed

    Cirillo, John; Rogasch, Nigel C; Semmler, John G

    2010-08-01

    The aim of this study was to examine corticomotor excitability and plasticity following repetitive thumb abduction training in left and right hands of young and old adults. Electromyographic recordings were obtained from the abductor pollicis brevis (APB) muscle of 12 young (aged 18-27 years) and 14 old (aged 63-75 years) adults. Motor training consisted of 300 ballistic abductions of the thumb to maximize peak abduction acceleration, with each hand tested in a separate session. Transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) was used to assess changes in contralateral APB motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before and after training. For young and old adults, APB MEP amplitude increased for both hands after training, which is indicative of use-dependent plasticity. However, the increase in MEP amplitude was 21% (P = 0.04) greater in the left (non-dominant) hand compared with the right (dominant) hand. This occurred despite a 40% greater improvement in peak thumb abduction acceleration (motor learning) for the right hand in young subjects compared with the left hand in young subjects (P < 0.04) and the right hand in old subjects (P < 0.01). Furthermore, no difference in use-dependent plasticity was observed between young and old adults, and SICI remained unchanged following ballistic training for both hands in all subjects. These findings suggest that there is greater strengthening of corticomotor circuits for control of the left compared with the right hand during simple ballistic thumb training and that an age-related decline in motor learning was observed only in the dominant hand. In contrast to previous studies, these data also indicate that young and old adults can demonstrate similar use-dependent corticomotor plasticity during this simple thumb-training task.

  10. Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain

    PubMed Central

    Urban, Kimberly R.; Gao, Wen-Jun

    2014-01-01

    Cognitive enhancement is perhaps one of the most intriguing and controversial topics in neuroscience today. Currently, the main classes of drugs used as potential cognitive enhancers include psychostimulants (methylphenidate (MPH), amphetamine), but wakefulness-promoting agents (modafinil) and glutamate activators (ampakine) are also frequently used. Pharmacologically, substances that enhance the components of the memory/learning circuits—dopamine, glutamate (neuronal excitation), and/or norepinephrine—stand to improve brain function in healthy individuals beyond their baseline functioning. In particular, non-medical use of prescription stimulants such as MPH and illicit use of psychostimulants for cognitive enhancement have seen a recent rise among teens and young adults in schools and college campuses. However, this enhancement likely comes with a neuronal, as well as ethical, cost. Altering glutamate function via the use of psychostimulants may impair behavioral flexibility, leading to the development and/or potentiation of addictive behaviors. Furthermore, dopamine and norepinephrine do not display linear effects; instead, their modulation of cognitive and neuronal function maps on an inverted-U curve. Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve. Finally, recent studies have begun to highlight potential damaging effects of stimulant exposure in healthy juveniles. This review explains how the main classes of cognitive enhancing drugs affect the learning and memory circuits, and highlights the potential risks and concerns in healthy individuals, particularly juveniles and adolescents. We emphasize the performance enhancement at the potential cost of brain plasticity that is associated with the neural ramifications of nootropic drugs in the healthy developing brain. PMID:24860437

  11. Altered short-term plasticity within the working memory neural network: Is it neuroticism or is it depression?

    PubMed

    Bianchi, Renzo; Laurent, Eric

    2016-04-01

    In the present article, we discuss (1) the importance of assessing and statistically considering both clinical and subclinical forms of depression when examining the relationship between neuroticism and short-term plasticity within the working memory neural network, and (2) the hypothesis of an antagonism between neuroticism and conscientiousness in personality research. We suggest that (1) neuroticism and depression should be examined in a relational manner, and (2) neuroticism and conscientiousness should not be antagonized.

  12. Training-Specific Neural Plasticity in Spinal Reflexes after Incomplete Spinal Cord Injury

    PubMed Central

    Patrick, Susan K.; Roy, Francois D.; Gorassini, Monica A.

    2016-01-01

    The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153. PMID:27725887

  13. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  14. Aerobic Exercise Effects on Ocular Dominance Plasticity with a Phase Combination Task in Human Adults

    PubMed Central

    Reynaud, Alexandre; Hess, Robert F.

    2017-01-01

    Several studies have shown that short-term monocular patching can induce ocular dominance plasticity in normal adults, in which the patched eye becomes stronger in binocular viewing. There is a recent study showing that exercise enhances this plasticity effect when assessed with binocular rivalry. We address one question, is this enhancement from exercise a general effect such that it is seen for measures of binocular processing other than that revealed using binocular rivalry? Using a binocular phase combination task in which we directly measure each eye's contribution to the binocularly fused percept, we show no additional effect of exercise after short-term monocular occlusion and argue that the enhancement of ocular dominance plasticity from exercise could not be demonstrated with our approach. PMID:28357142

  15. Adult Cortical Plasticity Studied with Chronically Implanted Electrode Arrays

    PubMed Central

    Abe, Hiroshi; McManus, Justin N.J.; Ramalingam, Nirmala; Li, Wu; Marik, Sally A.; Meyer zum Alten Borgloh, Stephan

    2015-01-01

    The functional architecture of adult cerebral cortex retains a capacity for experience-dependent change. This is seen after focal binocular lesions as rapid changes in receptive field (RF) of the lesion projection zone (LPZ) in the primary visual cortex (V1). To study the dynamics of the circuitry underlying these changes longitudinally, we implanted microelectrode arrays in macaque (Macaca mulatta) V1, eliminating the possibility of sampling bias, which was a concern in previous studies. With this method, we observed a rapid initial recovery in the LPZ and, during the following weeks, 63–89% of the sites in the LPZ showed recovery of visual responses with significant position tuning. The RFs shifted ∼3° away from the scotoma. In the absence of a lesion, visual stimulation surrounding an artificial scotoma did not elicit visual responses, suggesting that the postlesion RF shifts resulted from cortical reorganization. Interestingly, although both spikes and LFPs gave consistent prelesion position tuning, only spikes reflected the postlesion remapping. PMID:25673865

  16. Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment.

    PubMed

    Yang, Miyoung; Kim, Juhwan; Kim, Sung-Ho; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

    2012-07-25

    Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7-14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7-14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

  17. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    PubMed

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  18. Thalamocortical Projections onto Behaviorally Relevant Neurons Exhibit Plasticity during Adult Motor Learning.

    PubMed

    Biane, Jeremy S; Takashima, Yoshio; Scanziani, Massimo; Conner, James M; Tuszynski, Mark H

    2016-03-16

    Layer 5 neurons of the neocortex receive direct and relatively strong input from the thalamus. However, the intralaminar distribution of these inputs and their capacity for plasticity in adult animals are largely unknown. In slices of the primary motor cortex (M1), we simultaneously recorded from pairs of corticospinal neurons associated with control of distinct motor outputs: distal forelimb versus proximal forelimb. Activation of ChR2-expressing thalamocortical afferents in M1 before motor learning produced equivalent responses in monosynaptic excitation of neurons controlling the distal and proximal forelimb, suggesting balanced thalamic input at baseline. Following skilled grasp training, however, thalamocortical input shifted to bias activation of corticospinal neurons associated with control of the distal forelimb. This increase was associated with a cell-specific increase in mEPSC amplitude but not presynaptic release probability. These findings demonstrate distinct and highly segregated plasticity of thalamocortical projections during adult learning.

  19. Formation of cortical plasticity in older adults following tDCS and motor training.

    PubMed

    Goodwill, Alicia M; Reynolds, John; Daly, Robin M; Kidgell, Dawson J

    2013-01-01

    Neurodegeneration accompanies the process of natural aging, reducing the ability to perform functional daily activities. Transcranial direct current stimulation (tDCS) alters neuronal excitability and motor performance; however its beneficial effect on the induction of primary motor cortex (M1) plasticity in older adults is unclear. Moreover, little is known as to whether the tDCS electrode arrangement differentially affects M1 plasticity and motor performance in this population. In a double-blinded, cross-over trial, we compared unilateral, bilateral and sham tDCS combined with visuomotor tracking, on M1 plasticity and motor performance of the non-dominant upper limb, immediately post and 30 min following stimulation. We found (a) unilateral and bilateral tDCS decreased tracking error by 12-22% at both time points; with sham decreasing tracking error by 10% at 30 min only, (b) at both time points, motor evoked potentials (MEPs) were facilitated (38-54%) and short-interval intracortical inhibition was released (21-36%) for unilateral and bilateral conditions relative to sham, (c) there were no differences between unilateral and bilateral conditions for any measure. These findings suggest that tDCS modulated elements of M1 plasticity, which improved motor performance irrespective of the electrode arrangement. The results provide preliminary evidence indicating that tDCS is a safe non-invasive tool to preserve or improve neurological function and motor control in older adults.

  20. Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after a Stroke in the Somatosensory Cortex

    PubMed Central

    Kalogeraki, Evgenia; Pielecka-Fortuna, Justyna; Hüppe, Janika M.; Löwel, Siegrid

    2016-01-01

    The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in V1 declines with age and is compromised by a lesion in adjacent and distant cortical regions. In contrast, mice raised in an enriched environment (EE), exhibit lifelong OD plasticity and are protected from losing OD plasticity after a stroke-lesion in the somatosensory cortex. Since SC mice with an access to a running wheel (RW) displayed preserved OD plasticity during aging, we investigated whether physical exercise might also provide a plasticity promoting effect after a cortical stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity after stroke and also if short-term running after stroke restored OD plasticity to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD plasticity even after stroke, and a 2 weeks RW experience after stroke already restored lost OD plasticity. Additionally, the experience-enabled increase of the spatial frequency and contrast threshold of the optomotor reflex of the open eye, normally lost after a stroke, was restored in both groups of RW mice. Our data suggest that physical exercise alone can not only preserve visual plasticity into old age, but also restore it after a cortical stroke. PMID:27708575

  1. Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after a Stroke in the Somatosensory Cortex.

    PubMed

    Kalogeraki, Evgenia; Pielecka-Fortuna, Justyna; Hüppe, Janika M; Löwel, Siegrid

    2016-01-01

    The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in V1 declines with age and is compromised by a lesion in adjacent and distant cortical regions. In contrast, mice raised in an enriched environment (EE), exhibit lifelong OD plasticity and are protected from losing OD plasticity after a stroke-lesion in the somatosensory cortex. Since SC mice with an access to a running wheel (RW) displayed preserved OD plasticity during aging, we investigated whether physical exercise might also provide a plasticity promoting effect after a cortical stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity after stroke and also if short-term running after stroke restored OD plasticity to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD plasticity even after stroke, and a 2 weeks RW experience after stroke already restored lost OD plasticity. Additionally, the experience-enabled increase of the spatial frequency and contrast threshold of the optomotor reflex of the open eye, normally lost after a stroke, was restored in both groups of RW mice. Our data suggest that physical exercise alone can not only preserve visual plasticity into old age, but also restore it after a cortical stroke.

  2. Chronic Social Defeat Stress Modulates Dendritic Spines Structural Plasticity in Adult Mouse Frontal Association Cortex

    PubMed Central

    Shu, Yu

    2017-01-01

    Chronic stress is associated with occurrence of many mental disorders. Previous studies have shown that dendrites and spines of pyramidal neurons of the prefrontal cortex undergo drastic reorganization following chronic stress experience. So the prefrontal cortex is believed to play a key role in response of neural system to chronic stress. However, how stress induces dynamic structural changes in neural circuit of prefrontal cortex remains unknown. In the present study, we examined the effects of chronic social defeat stress on dendritic spine structural plasticity in the mouse frontal association (FrA) cortex in vivo using two-photon microscopy. We found that chronic stress altered spine dynamics in FrA and increased the connectivity in FrA neural circuits. We also found that the changes in spine dynamics in FrA are correlated with the deficit of sucrose preference in defeated mice. Our findings suggest that chronic stress experience leads to adaptive change in neural circuits that may be important for encoding stress experience related memory and anhedonia. PMID:28197343

  3. Differences in Feedback- and Inhibition-Related Neural Activity in Adult ADHD

    ERIC Educational Resources Information Center

    Dibbets, Pauline; Evers, Lisbeth; Hurks, Petra; Marchetta, Natalie; Jolles, Jelle

    2009-01-01

    The objective of this study was to examine response inhibition- and feedback-related neural activity in adults with attention deficit hyperactivity disorder (ADHD) using event-related functional MRI. Sixteen male adults with ADHD and 13 healthy/normal controls participated in this study and performed a modified Go/NoGo task. Behaviourally,…

  4. Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells.

    PubMed

    Farioli-Vecchioli, Stefano; Mattera, Andrea; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca; Saraulli, Daniele; Costanzi, Marco; Cestari, Vincenzo; Rouault, Jean-Pierre; Tirone, Felice

    2014-07-01

    Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis.

  5. Melatonin restores hippocampal neural precursor cell proliferation and prevents cognitive deficits induced by jet lag simulation in adult mice.

    PubMed

    Iggena, Deetje; Winter, York; Steiner, Barbara

    2017-05-01

    Frequent flyers and shift workers undergo circadian dysrhythmia with adverse impact on body and mind. The circadian rhythm disorder "jet lag" disturbs hippocampal neurogenesis and spatial cognition, which represent morphological and functional adult brain plasticity. This raises the question if pro-neurogenic stimuli might prevent those consequences. However, suitable measures to mitigate jet lag-induced adverse effects on brain plasticity have been neglected so far. Here, we used adult C57Bl6 mice to investigate the pro-neurogenic stimuli melatonin (8 mg/kg i.p.) as well as environmental enrichment as potential measures. We applied photoperiod alterations to simulate "jet lag" by shortening the dark period every third day by 6 hours for 3 weeks. We found that "jet lag" simulation reduced hippocampal neural precursor cell proliferation by 24% and impaired spatial memory performance in the water maze indicated by a prolonged swim path to the target (~23%). While melatonin prevented both the cellular (~1%) as well as the cognitive deficits (~5%), environmental enrichment only preserved precursor cell proliferation (~12%). Our results indicate that lifestyle interventions are insufficient to completely compensate jet lag-induced consequences. Instead, melatonin is required to prevent cognitive impairment caused by the same environmental factors to which frequent flyers and shift workers are typically exposed to.

  6. Normally occurring intersexuality and testosterone induced plasticity in the copulatory system of adult leopard geckos.

    PubMed

    Holmes, Melissa M; Putz, Oliver; Crews, David; Wade, Juli

    2005-04-01

    The copulatory neuromuscular system of lizards is highly sexually dimorphic. Adult males possess bilateral penises called hemipenes, which are independently controlled by two muscles, the retractor penis magnus (RPM) and transversus penis (TPN). These structures are not obvious in adult females. However, in adult female leopard geckos (Eublepharis macularius), testosterone induces hemipene growth. We investigated whether these structures develop de novo in adulthood or are histologically present as rudimentary structures in the female leopard gecko. We also investigated the extent of sexual dimorphisms and plasticity in the associated neuromuscular components. To do this, we compared copulatory morphology (sizes of hemipenes, RPM and TPN muscle fibers, and associated motoneurons, as well as motoneuron and RPM fiber number) in adult females treated with testosterone, control females, and control males. All of the geckos possessed hemipenes, RPMs and TPNs, but these structures were indeed vestigial in control females. Testosterone induced striking increases in hemipene and copulatory muscle fiber size in females, but not to levels equivalent to control males. In parallel, males with increased levels of androgenic activity had larger hemipenes, suggesting naturally occurring steroid-induced plasticity. Copulatory motoneurons were not sexually dimorphic in size or number, and these measures did not respond to testosterone. The data demonstrate that the copulatory system of leopard geckos, in which gonadal sex is determined by egg incubation temperature, differs from that of many species (both reptilian and mammalian) with genotypic sex determination. Indeed, the system is remarkable in that adult females have normally occurring intersex characteristics and they exhibit substantial steroid-induced morphological plasticity in adulthood.

  7. Examining neural plasticity and cognitive benefit through the unique lens of musical training.

    PubMed

    Moreno, Sylvain; Bidelman, Gavin M

    2014-02-01

    Training programs aimed to alleviate or improve auditory-cognitive abilities have either experienced mixed success or remain to be fully validated. The limited benefits of such regimens are largely attributable to our weak understanding of (i) how (and which) interventions provide the most robust and long lasting improvements to cognitive and perceptual abilities and (ii) how the neural mechanisms which underlie such abilities are positively modified by certain activities and experience. Recent studies indicate that music training provides robust, long-lasting biological benefits to auditory function. Importantly, the behavioral advantages conferred by musical experience extend beyond simple enhancements to perceptual abilities and even impact non-auditory functions necessary for higher-order aspects of cognition (e.g., working memory, intelligence). Collectively, preliminary findings indicate that alternative forms of arts engagement (e.g., visual arts training) may not yield such widespread enhancements, suggesting that music expertise uniquely taps and refines a hierarchy of brain networks subserving a variety of auditory as well as domain-general cognitive mechanisms. We infer that transfer from specific music experience to broad cognitive benefit might be mediated by the degree to which a listener's musical training tunes lower- (e.g., perceptual) and higher-order executive functions, and the coordination between these processes. Ultimately, understanding the broad impact of music on the brain will not only provide a more holistic picture of auditory processing and plasticity, but may help inform and tailor remediation and training programs designed to improve perceptual and cognitive benefits in human listeners.

  8. A spaceflight study of synaptic plasticity in adult rat vestibular maculas

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1994-01-01

    Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but

  9. Comparing Individual Differences in Inconsistency and Plasticity as Predictors of Cognitive Function in Older Adults

    PubMed Central

    Grand, Jacob H.G.; Stawski, Robert S.; MacDonald, Stuart W.S.

    2016-01-01

    Introduction Recent theorizing differentiates key constraints on cognition, including one’s current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. Method Participants included 304 adults (aged 64 to 92 years: M=74.02, SD=5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time measures (choice RT and one-back choice RT), baseline measures of response time (RT) inconsistency (intraindividual standard deviation (ISD) across-trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed, and then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6 year) rates of cognitive change. Results Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. Conclusions These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults. PMID:26898536

  10. The sexual identity of adult intestinal stem cells controls organ size and plasticity

    PubMed Central

    Hudry, Bruno; Khadayate, Sanjay; Miguel-Aliaga, Irene

    2016-01-01

    SUMMARY Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realisation that cell-intrinsic mechanisms play important and persistent roles1,2. Here we use the Drosophila melanogaster intestine to investigate the nature and significance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncover its key roles in controlling organ size, its reproductive plasticity and its response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms, which control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognised. PMID:26887495

  11. Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning.

    PubMed

    Donato, Flavio; Rompani, Santiago Belluco; Caroni, Pico

    2013-12-12

    Learning and memory processes can be influenced by recent experience, but the mechanisms involved are poorly understood. Enhanced plasticity during critical periods of early life is linked to differentiating parvalbumin (PV)-interneuron networks, suggesting that recent experience may modulate learning by targeting the differentiation state of PV neurons in the adult. Here we show that environmental enrichment and Pavlovian contextual fear conditioning induce opposite, sustained and reversible hippocampal PV-network configurations in adult mice. Specifically, enrichment promotes the emergence of large fractions of low-differentiation (low PV and GAD67 expression) basket cells with low excitatory-to-inhibitory synaptic-density ratios, whereas fear conditioning leads to large fractions of high-differentiation (high PV and GAD67 expression) basket cells with high excitatory-to-inhibitory synaptic-density ratios. Pharmacogenetic inhibition or activation of PV neurons was sufficient to induce such opposite low-PV-network or high-PV-network configurations, respectively. The low-PV-network configuration enhanced structural synaptic plasticity, and memory consolidation and retrieval, whereas these were reduced by the high-PV-network configuration. We then show that maze navigation learning induces a hippocampal low-PV-network configuration paralleled by enhanced memory and structural synaptic plasticity throughout training, followed by a shift to a high-PV-network configuration after learning completion. The shift to a low-PV-network configuration specifically involved increased vasoactive intestinal polypeptide (VIP)-positive GABAergic boutons and synaptic transmission onto PV neurons. Closely comparable low- and high-PV-network configurations involving VIP boutons were specifically induced in primary motor cortex upon rotarod motor learning. These results uncover a network plasticity mechanism induced after learning through VIP-PV microcircuit modulation, and involving

  12. NF-KappaB in Long-Term Memory and Structural Plasticity in the Adult Mammalian Brain

    PubMed Central

    Kaltschmidt, Barbara; Kaltschmidt, Christian

    2015-01-01

    The transcription factor nuclear factor kappaB (NF-κB) is a well-known regulator of inflammation, stress, and immune responses as well as cell survival. In the nervous system, NF-κB is one of the crucial components in the molecular switch that converts short- to long-term memory—a process that requires de novo gene expression. Here, the researches published on NF-κB and downstream target genes in mammals will be reviewed, which are necessary for structural plasticity and long-term memory, both under normal and pathological conditions in the brain. Genetic evidence has revealed that NF-κB regulates neuroprotection, neuronal transmission, and long-term memory. In addition, after genetic ablation of all NF-κB subunits, a severe defect in hippocampal adult neurogenesis was observed during aging. Proliferation of neural precursors is increased; however, axon outgrowth, synaptogenesis, and tissue homeostasis of the dentate gyrus are hampered. In this process, the NF-κB target gene PKAcat and other downstream target genes such as Igf2 are critically involved. Therefore, NF-κB activity seems to be crucial in regulating structural plasticity and replenishment of granule cells within the hippocampus throughout the life. In addition to the function of NF-κB in neurons, we will discuss on a neuroinflammatory role of the transcription factor in glia. Finally, a model for NF-κB homeostasis on the molecular level is presented, in order to explain seemingly the contradictory, the friend or foe, role of NF-κB in the nervous system. PMID:26635522

  13. Selectivity of flesh-footed shearwaters for plastic colour: Evidence for differential provisioning in adults and fledglings.

    PubMed

    Lavers, Jennifer L; Bond, Alexander L

    2016-02-01

    The ingestion of plastic by seabirds has been used as an indicator of population and ocean health. However, few studies have examined adults and juveniles of the same species concurrent with the availability of plastic in the local marine environment. In King George Sound (KGS), Western Australia, 13% of adult flesh-footed shearwaters (Ardenna carneipes) and 90% of fledglings contained plastic items in their digestive tract. On Lord Howe Island (LHI), New South Wales, 75% of adult shearwaters and 100% of fledglings contained plastic. Ingested items were assessed using Jaccard's Index (where J = 0 indicates complete dissimilarity and J = 1 complete similarity). The colour of items ingested by self- and chick-provisioning shearwaters from KGS exhibited broad overlap with plastic available in the local environment (J = 0.78-0.80), and plastic in adults and fledglings from LHI were less similar to those available (J = 0.31-0.58). Additional data on seabird colour selection would improve our understanding of the factors influencing the behaviour of ingesting plastic, and its contribution to the decline of some species.

  14. Neural Correlates Associated with Successful Working Memory Performance in Older Adults as Revealed by Spatial ICA

    PubMed Central

    Saliasi, Emi; Geerligs, Linda; Lorist, Monicque M.; Maurits, Natasha M.

    2014-01-01

    To investigate which neural correlates are associated with successful working memory performance, fMRI was recorded in healthy younger and older adults during performance on an n-back task with varying task demands. To identify functional networks supporting working memory processes, we used independent component analysis (ICA) decomposition of the fMRI data. Compared to younger adults, older adults showed a larger neural (BOLD) response in the more complex (2-back) than in the baseline (0-back) task condition, in the ventral lateral prefrontal cortex (VLPFC) and in the right fronto-parietal network (FPN). Our results indicated that a higher BOLD response in the VLPFC was associated with increased performance accuracy in older adults, in both the baseline and the more complex task condition. This ‘BOLD-performance’ relationship suggests that the neural correlates linked with successful performance in the older adults are not uniquely related to specific working memory processes present in the complex but not in the baseline task condition. Furthermore, the selective presence of this relationship in older but not in younger adults suggests that increased neural activity in the VLPFC serves a compensatory role in the aging brain which benefits task performance in the elderly. PMID:24911016

  15. Maternal dietary loads of α-tocopherol depress protein kinase C signaling and synaptic plasticity in rat postnatal developing hippocampus and promote permanent deficits in adult offspring.

    PubMed

    Betti, Michele; Ambrogini, Patrizia; Minelli, Andrea; Floridi, Alessandro; Lattanzi, Davide; Ciuffoli, Stefano; Bucherelli, Corrado; Prospero, Emilia; Frontini, Andrea; Santarelli, Lory; Baldi, Elisabetta; Benetti, Fernando; Galli, Francesco; Cuppini, Riccardo

    2011-01-01

    Vitamin E (α-tocopherol) supplementation has been tested as prophylaxis against gestational disorders associated with oxidative damage. However, recent evidence showing that high maternal α-tocopherol intake can adversely affect offspring development raises concerns on the safety of vitamin E extradosages during pregnancy. Besides acting as an antioxidant, α-tocopherol depresses cell proliferation and modulates cell signaling through inhibiting protein kinase C (PKC), a kinase that is deeply involved in neural maturation and plasticity. Possible effects of α-tocopherol loads in the maturing brain, where PKC dysregulation is associated to developmental dysfunctions, are poorly known. Here, supranutritional doses of α-tocopherol were fed to pregnant and lactating dams to evaluate the effects on PKC signaling and morphofunctional maturation in offspring hippocampus. Results showed that maternal supplementation potentiates hippocampal α-tocopherol incorporation in offspring and leads to marked decrease of PKC phosphorylation throughout postnatal maturation, accompanied by reduced phosphorylation of growth-associated protein-43 and myristoylated alanine-rich C kinase substrate, two PKC substrates involved in neural development and plasticity. Although processes of neuronal maturation, synapse formation and targeting appeared unaffected, offspring of supplemented mothers displayed a marked reduction of long-term synaptic plasticity in juvenile hippocampus. Interestingly, this impairment persisted in adulthood, when a deficit in hippocampus-dependent, long-lasting spatial memory was also revealed. In conclusion, maternal supplementation with elevated doses of α-tocopherol can influence cell signaling and synaptic plasticity in developing hippocampus and promotes permanent adverse effects in adult offspring. The present results emphasize the need to evaluate the safety of supranutritional maternal intake of α-tocopherol in humans.

  16. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

    PubMed Central

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-01-01

    The ‘neural plate border’ of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure. DOI: http://dx.doi.org/10.7554/eLife.21620.001 PMID:28355135

  17. Adult plasticity of cold tolerance in a continental-temperate population of Drosophila suzukii.

    PubMed

    Jakobs, Ruth; Gariepy, Tara D; Sinclair, Brent J

    2015-08-01

    Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a worldwide emerging pest of soft fruits, but its cold tolerance has not been thoroughly explored. We determined the cold tolerance strategy, low temperature thermal limits, and plasticity of cold tolerance in both male and female adult D. suzukii. We reared flies under common conditions (long days, 21°C; control) and induced plasticity by rapid cold-hardening (RCH, 1h at 0°C followed by 1h recovery), cold acclimation (CA, 5 days at 6°C) or acclimation under fluctuating temperatures (FA). D. suzukii had supercooling points (SCPs) between -16 and -23°C, and were chill-susceptible. 80% of control flies were killed after 1h at -7.2°C (males) or -7.5°C (females); CA and FA improved survival of this temperature in both sexes, but RCH did not. 80% of control flies were killed after 70 h (male) or 92 h (female) at 0°C, and FA shifted this to 112 h (males) and 165 h (females). FA flies entered chill coma (CTmin) at approximately -1.7°C, which was ca. 0.5°C colder than control flies; RCH and CA increased the CTmin compared to controls. Control and RCH flies exposed to 0°C for 8h took 30-40 min to recover movement, but this was reduced to <10 min in CA and FA. Flies placed outside in a field cage in London, Ontario, were all killed by a transient cold snap in December. We conclude that adult phenotypic plasticity is not sufficient to allow D. suzukii to overwinter in temperate habitats, and suggest that flies could overwinter in association with built structures, or that there may be additional cold tolerance imparted by developmental plasticity.

  18. Cofilin1 Controls Transcolumnar Plasticity in Dendritic Spines in Adult Barrel Cortex

    PubMed Central

    Tsubota, Tadashi; Okubo-Suzuki, Reiko; Ohashi, Yohei; Tamura, Keita; Ogata, Koshin; Yaguchi, Masae; Matsuyama, Makoto; Inokuchi, Kaoru; Miyashita, Yasushi

    2015-01-01

    During sensory deprivation, the barrel cortex undergoes expansion of a functional column representing spared inputs (spared column), into the neighboring deprived columns (representing deprived inputs) which are in turn shrunk. As a result, the neurons in a deprived column simultaneously increase and decrease their responses to spared and deprived inputs, respectively. Previous studies revealed that dendritic spines are remodeled during this barrel map plasticity. Because cofilin1, a predominant regulator of actin filament turnover, governs both the expansion and shrinkage of the dendritic spine structure in vitro, it hypothetically regulates both responses in barrel map plasticity. However, this hypothesis remains untested. Using lentiviral vectors, we knocked down cofilin1 locally within layer 2/3 neurons in a deprived column. Cofilin1-knocked-down neurons were optogenetically labeled using channelrhodopsin-2, and electrophysiological recordings were targeted to these knocked-down neurons. We showed that cofilin1 knockdown impaired response increases to spared inputs but preserved response decreases to deprived inputs, indicating that cofilin1 dependency is dissociated in these two types of barrel map plasticity. To explore the structural basis of this dissociation, we then analyzed spine densities on deprived column dendritic branches, which were supposed to receive dense horizontal transcolumnar projections from the spared column. We found that spine number increased in a cofilin1-dependent manner selectively in the distal part of the supragranular layer, where most of the transcolumnar projections existed. Our findings suggest that cofilin1-mediated actin dynamics regulate functional map plasticity in an input-specific manner through the dendritic spine remodeling that occurs in the horizontal transcolumnar circuits. These new mechanistic insights into transcolumnar plasticity in adult rats may have a general significance for understanding reorganization of

  19. Environment- and activity-dependent dopamine neurotransmitter plasticity in the adult substantia nigra.

    PubMed

    Aumann, Tim D

    2016-04-01

    The ability of neurons to change the amount or type of neurotransmitter they use, or 'neurotransmitter plasticity', is an emerging new form of adult brain plasticity. For example, it has recently been shown that neurons in the adult rat hypothalamus up- or down-regulate dopamine (DA) neurotransmission in response to the amount of light the animal receives (photoperiod), and that this in turn affects anxiety- and depressive-like behaviors (Dulcis et al., 2013). In this Chapter I consolidate recent evidence from my laboratory suggesting neurons in the adult mouse substantia nigra pars compacta (SNc) also undergo DA neurotransmitter plasticity in response to persistent changes in their electrical activity, including that driven by the mouse's environment or behavior. Specifically, we have shown that the amounts of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) gene promoter activity, TH mRNA and TH protein in SNc neurons increases or decreases after ∼20h of altered electrical activity. Also, infusion of ion-channel agonists or antagonists into the midbrain for 2 weeks results in ∼10% (∼500 neurons) more or fewer TH immunoreactive (TH+) SNc neurons, with no change in the total number of SNc neurons (TH+ and TH-). Targeting ion-channels mediating cell-autonomous pacemaker activity in, or synaptic input and afferent pathways to, SNc neurons are equally effective in this regard. In addition, exposing mice to different environments (sex pairing or environment enrichment) for 1-2 weeks induces ∼10% more or fewer TH+ SNc (and ventral tegmental area or VTA) neurons and this is abolished by concurrent blockade of synaptic transmission in midbrain. Although further research is required to establish SNc (and VTA) DA neurotransmitter plasticity, and to determine whether it alters brain function and behavior, it is an exciting prospect because: (1) It may play important roles in movement, motor learning, reward, motivation, memory and cognition; and (2

  20. Interactions between chronic ethanol consumption and thiamine deficiency on neural plasticity, spatial memory and cognitive flexibility

    PubMed Central

    Vedder, Lindsey C.; Hall, Joseph M.; Jabrouin, Kimberly R.; Savage, Lisa M.

    2015-01-01

    Background Many alcoholics display moderate to severe cognitive dysfunction accompanied by brain pathology. A factor confounded with prolonged heavy alcohol consumption is poor nutrition and many alcoholics are thiamine deficient. Thus, thiamine deficiency (TD) has emerged as a key factor underlying alcohol–related brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can progress into Wernicke–Korsakoff Syndrome and these disorders have a high prevalence among alcoholics. Animal models are critical for determining the exact contributions of ethanol- and TD-induced neurotoxicity, as well as the interactions of those factors to brain and cognitive dysfunction. Methods Adult rats were randomly assigned to one of six treatment conditions: Chronic ethanol treatment (CET) where rats consumed a 20% v/v solution of ethanol over 6 months; Severe pyrithiamine-induced TD (PTD-MAS); Moderate PTD (PTD-EAS); Moderate PTD followed by CET (PTD-CET); Moderate PTD during CET (CET-PTD); Pair-fed control (PF). After recovery from treatment, all rats were tested on spontaneous alternation and attentional set-shifting. After behavioral testing, brains were harvested for determination of mature brain-derived neurotrophic factor (BDNF) and thalamic pathology. Results Moderate TD combined with CET, regardless of treatment order, produced significant impairments in spatial memory, cognitive flexibility and reductions in brain plasticity as measured by BDNF levels in the frontal cortex and hippocampus. These alterations are greater than those seen in moderate TD alone and the synergistic effects of moderate TD with CET leads to a unique cognitive profile. However, CET did not exacerbate thalamic pathology seen after moderate TD. Conclusions These data support the emerging theory that subclinical TD during chronic heavy alcohol consumption is critical for the development of significant cognitive impairment associated with ARBD. PMID:26419807

  1. Developmental neural plasticity and its cognitive benefits: olivocerebellar reinnervation compensates for spatial function in the cerebellum.

    PubMed

    Willson, Melina L; Bower, Adrian J; Sherrard, Rachel M

    2007-03-01

    The adult mammalian central nervous system displays limited reinnervation and recovery from trauma. However, during development, post-lesion plasticity may generate alternative paths, thus providing models to investigate reinnervation and repair. After unilateral transection of the neonatal rat olivocerebellar path (pedunculotomy), axons from the remaining inferior olive reinnervate the denervated hemicerebellum. Unfortunately, reinnervation to the cerebellar hemisphere is incomplete; therefore, its capacity to mediate hemispheric function (navigation) is unknown. We studied sensorimotor control and spatial cognition of rats with and without transcommissural reinnervation using simple (bridge and ladder) and complex (wire) locomotion tests and the Morris water maze (hidden, probe and cued paradigms). Although pedunculotomized animals completed locomotory tasks more slowly than controls, all groups performed equally in the cued maze, indicating that lesioned animals could orientate to and reach the platform. In animals pedunculotomized on day 3 (Px3), which develop olivocerebellar reinnervation, final spatial knowledge was as good as controls, although they learned more erratically, failing to retain all information from one day to the next. By contrast, animals pedunculotomized on day 11 (Px11), which do not develop reinnervation, did not learn the task, taking less direct routes and more time to reach the platform than controls. In the probe test, control and Px3, but not Px11, animals swam directly to the remembered location. Furthermore, the amount of transcommissural reinnervation to the denervated hemisphere correlated directly with spatial performance. These results show that transcommissural olivocerebellar reinnervation is associated with spatial learning, i.e. even partial circuit repair confers significant functional benefit.

  2. The relative contributions of developmental plasticity and adult acclimation to physiological variation in the tsetse fly, Glossina pallidipes (Diptera, Glossinidae)

    PubMed Central

    Terblanche, John S.; Chown, Steven L.

    2006-01-01

    Summary Recent reviews of the adaptive hypotheses for animal responses to acclimation have highlighted the importance of distinguishing between developmental and adult (non-developmental) phenotypic plasticity. However, little work has been undertaken separating the effects of developmental plasticity from adult acclimation in physiological traits. Therefore, we investigate the relative contributions of these two distinct forms of plasticity to the environmental physiology of adult tsetse flies by exposing developing pupae or adult flies to different temperatures and comparing their responses. We also exposed flies to different temperatures during development and re-exposed them as adults to the same temperatures to investigate possible cumulative effects. Critical thermal maxima were relatively inflexible in response to acclimation temperatures (21, 25, 29 °C) with plasticity type accounting for the majority of the variation (49-67 %, nested ANOVA). By contrast, acclimation had a larger effect on critical thermal minima with treatment temperature accounting for most of the variance (84-92 %). Surprisingly little of the variance in desiccation rate could be explained by plasticity type (30-47 %). The only significant effect of acclimation on standard (resting) metabolic rate of adult flies occurred in response to 21 °C, resulting in treatment temperature, rather than plasticity type, accounting for the majority of the variance (30-76 %). This study demonstrates that the stage at which acclimation takes place has significant, though often different effects on several adult physiological traits in G. pallidipes, and therefore that it is not only important to consider the form of plasticity but also the direction of the response and its significance from a life-history perspective. PMID:16513933

  3. Plasticity and Adult Neurogenesis in Amphibians and Reptiles: More Questions than Answers.

    PubMed

    Powers, Alice Schade

    2016-08-24

    Studies of the relationship between behavioral plasticity and new cells in the adult brain in amphibians and reptiles are sparse but demonstrate that environmental and hormonal variables do have an effect on the amount of cell proliferation and/or migration. The variables that are reviewed here are: enriched environment, social stimulation, spatial area use, season, photoperiod and temperature, and testosterone. Fewer data are available for amphibians than for reptiles, but for both groups many issues are still to be resolved. It is to be hoped that the questions raised here will generate more answers in future studies.

  4. Culture bag systems for clinical applications of adult human neural crest-derived stem cells

    PubMed Central

    2014-01-01

    Introduction Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. Methods We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. Results When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as

  5. Neural correlates of single word reading in bilingual children and adults.

    PubMed

    Hernandez, Arturo E; Woods, Elizabeth A; Bradley, Kailyn A L

    2015-04-01

    The present study compared the neural correlates of language processing in children and adult Spanish-English bilinguals. Participants were asked to perform a visual lexical processing task in both Spanish and English while being scanned with fMRI. Both children and adults recruited a similar network of left hemisphere "language" areas and showed similar proficiency profiles in Spanish. In terms of behavior, adults showed better language proficiency in English relative to children. Furthermore, neural activity in adults was observed in the bilateral MTG. Age-related differences were observed in Spanish in the right MTG. The current results confirm the presence of neural activity in a set of left hemisphere areas in both adult and child bilinguals when reading words in each language. They also reveal that differences in neural activity are not entirely driven by changes in language proficiency during visual word processing. This indicates that both skill development and age can play a role in brain activity seen across development.

  6. Exercise-Induced Fitness Changes Correlate with Changes in Neural Specificity in Older Adults.

    PubMed

    Kleemeyer, Maike M; Polk, Thad A; Schaefer, Sabine; Bodammer, Nils C; Brechtel, Lars; Lindenberger, Ulman

    2017-01-01

    Neural specificity refers to the degree to which neural representations of different stimuli can be distinguished. Evidence suggests that neural specificity, operationally defined as stimulus-related differences in functional magnetic resonance imaging (fMRI) activation patterns, declines with advancing adult age, and that individual differences in neural specificity are associated with individual differences in fluid intelligence. A growing body of literature also suggests that regular physical activity may help preserve cognitive abilities in old age. Based on this literature, we hypothesized that exercise-induced improvements in fitness would be associated with greater neural specificity among older adults. A total of 52 adults aged 59-74 years were randomly assigned to one of two aerobic-fitness training regimens, which differed in intensity. Participants in both groups trained three times a week on stationary bicycles. In the low-intensity (LI) group, the resistance was kept constant at a low level (10 Watts). In the high-intensity (HI) group, the resistance depended on participants' heart rate and therefore typically increased with increasing fitness. Before and after the 6-month training phase, participants took part in a functional MRI experiment in which they viewed pictures of faces and buildings. We used multivariate pattern analysis (MVPA) to estimate the distinctiveness of neural activation patterns in ventral visual cortex (VVC) evoked by face or building stimuli. Fitness was also assessed before and after training. In line with our hypothesis, training-induced changes in fitness were positively associated with changes in neural specificity. We conclude that physical activity may protect against age-related declines in neural specificity.

  7. Exercise-Induced Fitness Changes Correlate with Changes in Neural Specificity in Older Adults

    PubMed Central

    Kleemeyer, Maike M.; Polk, Thad A.; Schaefer, Sabine; Bodammer, Nils C.; Brechtel, Lars; Lindenberger, Ulman

    2017-01-01

    Neural specificity refers to the degree to which neural representations of different stimuli can be distinguished. Evidence suggests that neural specificity, operationally defined as stimulus-related differences in functional magnetic resonance imaging (fMRI) activation patterns, declines with advancing adult age, and that individual differences in neural specificity are associated with individual differences in fluid intelligence. A growing body of literature also suggests that regular physical activity may help preserve cognitive abilities in old age. Based on this literature, we hypothesized that exercise-induced improvements in fitness would be associated with greater neural specificity among older adults. A total of 52 adults aged 59–74 years were randomly assigned to one of two aerobic-fitness training regimens, which differed in intensity. Participants in both groups trained three times a week on stationary bicycles. In the low-intensity (LI) group, the resistance was kept constant at a low level (10 Watts). In the high-intensity (HI) group, the resistance depended on participants’ heart rate and therefore typically increased with increasing fitness. Before and after the 6-month training phase, participants took part in a functional MRI experiment in which they viewed pictures of faces and buildings. We used multivariate pattern analysis (MVPA) to estimate the distinctiveness of neural activation patterns in ventral visual cortex (VVC) evoked by face or building stimuli. Fitness was also assessed before and after training. In line with our hypothesis, training-induced changes in fitness were positively associated with changes in neural specificity. We conclude that physical activity may protect against age-related declines in neural specificity. PMID:28360850

  8. Neural Mechanisms Underlying Action Observation in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Virji-Babul, Naznin; Moiseev, Alexander; Cheung, Teresa; Weeks, Daniel J.; Cheyne, Douglas; Ribary, Urs

    2010-01-01

    Results of a magnetoencephalography (MEG) brain imaging study conducted to examine the cortical responses during action execution and action observation in 10 healthy adults and 8 age-matched adults with Down syndrome are reported. During execution, the motor responses were strongly lateralized on the ipsilateral rather than the contralateral side…

  9. Activity-Dependent Plasticity and Gene Expression Modifications in the Adult CNS

    PubMed Central

    Carulli, Daniela; Foscarin, Simona; Rossi, Ferdinando

    2011-01-01

    Information processing, memory formation, or functional recovery after nervous system damage depend on the ability of neurons to modify their functional properties or their connections. At the cellular/molecular level, structural modifications of neural circuits are finely regulated by intrinsic neuronal properties and growth-regulatory cues in the extracellular milieu. Recently, it has become clear that stimuli coming from the external world, which comprise sensory inflow, motor activity, cognitive elaboration, or social interaction, not only provide the involved neurons with instructive information needed to shape connection patterns to sustain adaptive function, but also exert a powerful influence on intrinsic and extrinsic growth-related mechanisms, so to create permissive conditions for neuritic remodeling. Here, we present an overview of recent findings concerning the effects of experience on molecular mechanisms underlying CNS structural plasticity, both in physiological conditions and after damage, with particular focus on activity-dependent modulation of growth-regulatory genes and epigenetic modifications. PMID:22144945

  10. Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice.

    PubMed

    Han, Xiaoning; Chen, Michael; Wang, Fushun; Windrem, Martha; Wang, Su; Shanz, Steven; Xu, Qiwu; Oberheim, Nancy Ann; Bekar, Lane; Betstadt, Sarah; Silva, Alcino J; Takano, Takahiro; Goldman, Steven A; Nedergaard, Maiken

    2013-03-07

    Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.

  11. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-11-26

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur.

  12. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

    PubMed Central

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. DOI: http://dx.doi.org/10.7554/eLife.11290.001 PMID:26609811

  13. Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells.

    PubMed

    Aiba, Kazuhiro; Sharov, Alexei A; Carter, Mark G; Foroni, Chiara; Vescovi, Angelo L; Ko, Minoru S H

    2006-04-01

    To understand global features of gene expression changes during in vitro neural differentiation, we carried out the microarray analysis of embryonic stem cells (ESCs), embryonal carcinoma cells, and adult neural stem/progenitor (NS) cells. Expression profiling of ESCs during differentiation in monolayer culture revealed three distinct phases: undifferentiated ESCs, primitive ectoderm-like cells, and neural progenitor cells. Principal component (PC) analysis revealed that these cells were aligned on PC1 over the course of 6 days. This PC1 represents approximately 4,000 genes, the expression of which increased with neural commitment/differentiation. Furthermore, NS cells derived from adult brain and their differentiated cells were positioned along this PC axis further away from undifferentiated ESCs than embryonic stem-derived neural progenitors. We suggest that this PC1 defines a path to neural fate, providing a scale for the degree of commitment/differentiation.

  14. In vivo BDNF modulation of adult functional and morphological synaptic plasticity at hippocampal mossy fibers.

    PubMed

    Gómez-Palacio-Schjetnan, Andrea; Escobar, Martha L

    2008-11-07

    Brain-derived neurotrophic factor (BDNF) has been proposed as a key regulator and mediator of long-term synaptic modifications related to learning and memory maintenance. Our previous studies show that application of high-frequency stimulation (HFS) sufficient to elicit LTP at the dentate gyrus (DG)-CA3 pathway produces mossy fiber structural modifications 7 days after tetanic stimulation. In the present study, we show that acute intrahippocampal microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the DG-CA3 projection of anesthetized adult rats. Furthermore, we show that BDNF functional modifications in synaptic efficacy are accompanied by a presynaptic structural long-lasting reorganization at the hippocampal mossy fiber pathway. These findings support the idea that BDNF plays an important role as synaptic messenger of activity-dependent synaptic plasticity in the adult mammalian brain, in vivo.

  15. The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis.

    PubMed

    Ortega-Martínez, Sylvia; Trejo, José L

    2015-02-15

    The relevance of adult neurogenesis in hippocampal function is well documented, as is the potential impact stress has on the adult neurogenic niche. Adult born neurons are generated from neural precursors in the dentate gyrus (DG), although the point in postnatal development that these cell precursors originate is not known. This is particularly relevant if we consider the effects stress may have on the development of neural precursors, and whether such effects on adult neurogenesis and behavior may persist in the long-term. We have analyzed the proportion of neural precursors in the adult murine hippocampus born on specific days during postnatal development using a dual birth-dating analysis, and we assessed their sensitivity to dexamethasone (DEX) on the peak day of cell generation. We also studied the consequences of postnatal DEX administration on adult hippocampal-dependent behavior. Postnatal day 6 (P6) is a preferred period for proliferating neural stem cells (NSCs) to become the precursors that remain in a proliferative state throughout adulthood. This window is independent of gender, the cell's location in the DG granule cell layer or their rostro-caudal position. DEX administration at P6 reduces the size of the adult NSC pool in the DG, which is correlated with poor learning/memory capacity and increased anxiety-like behavior. These results indicate that aNSCs are generated non-uniformly during postnatal development, with peak generation on day P6, and that stress receptor activation during the key period of postnatal NSC generation has a profound impact on both adult hippocampal neurogenesis and behavior.

  16. Neural plasticity in hypocretin neurons: the basis of hypocretinergic regulation of physiological and behavioral functions in animals

    PubMed Central

    Gao, Xiao-Bing; Hermes, Gretchen

    2015-01-01

    The neuronal system that resides in the perifornical and lateral hypothalamus (Pf/LH) and synthesizes the neuropeptide hypocretin/orexin participates in critical brain functions across species from fish to human. The hypocretin system regulates neural activity responsible for daily functions (such as sleep/wake homeostasis, energy balance, appetite, etc.) and long-term behavioral changes (such as reward seeking and addiction, stress response, etc.) in animals. The most recent evidence suggests that the hypocretin system undergoes substantial plastic changes in response to both daily fluctuations (such as food intake and sleep-wake regulation) and long-term changes (such as cocaine seeking) in neuronal activity in the brain. The understanding of these changes in the hypocretin system is essential in addressing the role of the hypocretin system in normal physiological functions and pathological conditions in animals and humans. In this review, the evidence demonstrating that neural plasticity occurs in hypocretin-containing neurons in the Pf/LH will be presented and possible physiological, behavioral, and mental health implications of these findings will be discussed. PMID:26539086

  17. Evolutionarily-conserved role of the NF-kappaB transcription factor in neural plasticity and memory.

    PubMed

    Romano, Arturo; Freudenthal, Ramiro; Merlo, Emiliano; Routtenberg, Aryeh

    2006-09-01

    NF-kappaB is an evolutionarily conserved family of transcription factors (TFs) critically involved in basic cellular mechanisms of the immune response, inflammation, development and apoptosis. In spite of the fact that it is expressed in the central nervous system, particularly in areas involved in memory processing, and is activated by signals such as glutamate and Ca2+, its role in neural plasticity and memory has only recently become apparent. A surprising feature of this molecule is its presence within the synapse. An increasing number of reports have called attention to the role of this TF in processes that require long-term regulation of the synaptic function underlying memory and neural plasticity. Here we review the evidence regarding a dual role for NF-kappaB, as both a signalling molecule after its activation at the synapse and a transcriptional regulator upon reaching the nucleus. The specific role of this signal, as well as the general transcriptional mechanism, in the process of memory formation is discussed. Converging lines of evidence summarized here point to a pivotal role for the NF-kappaB transcription factor as a direct signalling mechanism in the regulation of gene expression involved in long-term memory.

  18. Comprehensive neural networks for guilty feelings in young adults.

    PubMed

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-01-15

    Feelings of guilt are associated with widespread self and social cognitions, e.g., empathy, moral reasoning, and punishment. Neural correlates directly related to the degree of feelings of guilt have not been detected, probably due to the small numbers of subjects, whereas there are growing numbers of neuroimaging studies of feelings of guilt. We hypothesized that the neural networks for guilty feelings are widespread and include the insula, inferior parietal lobule (IPL), amygdala, subgenual cingulate cortex (SCC), and ventromedial prefrontal cortex (vmPFC), which are essential for cognitions of guilt. We investigated the association between regional gray matter density (rGMD) and feelings of guilt in 764 healthy young students (422 males, 342 females; 20.7 ± 1.8 years) using magnetic resonance imaging and the guilty feeling scale (GFS) for the younger generation which comprises interpersonal situation (IPS) and rule-breaking situation (RBS) scores. Both the IPS and RBS were negatively related to the rGMD in the right posterior insula (PI). The IPS scores were negatively correlated with rGMD in the left anterior insula (AI), right IPL, and vmPFC using small volume correction. A post hoc analysis performed on the significant clusters identified through these analyses revealed that rGMD activity in the right IPL showed a significant negative association with the empathy quotient. These findings at the whole-brain level are the widespread comprehensive neural network regions for guilty feelings. Interestingly, the novel finding in this study is that the PI was implicated as a common region for feelings of guilt with interaction between the IPS and RBS. Additionally, the neural networks including the IPL were associated with empathy and with regions implicated in moral reasoning (AI and vmPFC), and punishment (AI).

  19. The Neural Representation of Consonant-Vowel Transitions in Adults Who Wear Hearing Aids

    PubMed Central

    Tremblay, Kelly L.; Kalstein, Laura; Billings, Cuttis J.; Souza, Pamela E.

    2006-01-01

    Hearing aids help compensate for disorders of the ear by amplifying sound; however, their effectiveness also depends on the central auditory system's ability to represent and integrate spectral and temporal information delivered by the hearing aid. The authors report that the neural detection of time-varying acoustic cues contained in speech can be recorded in adult hearing aid users using the acoustic change complex (ACC). Seven adults (50–76 years) with mild to severe sensorineural hearing participated in the study. When presented with 2 identifiable consonant-vowel (CV) syllables (“shee” and “see”), the neural detection of CV transitions (as indicated by the presence of a P1-N1-P2 response) was different for each speech sound. More specifically, the latency of the evoked neural response coincided in time with the onset of the vowel, similar to the latency patterns the authors previously reported in normal-hearing listeners. PMID:16959736

  20. Neural Correlates of Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Vasic, Nenad; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Wolf, Robert Christian

    2008-01-01

    Behavioral studies indicate deficits in phonological working memory (WM) and executive functioning in dyslexics. However, little is known about the underlying functional neuroanatomy. In the present study, neural correlates of WM in adolescents and young adults with dyslexia were investigated using event-related functional magnetic resonance…

  1. The Neural Basis of Sustained and Transient Attentional Control in Young Adults with ADHD

    ERIC Educational Resources Information Center

    Banich, Marie T.; Burgess, Gregory C.; Depue, Brendan E.; Ruzic, Luka; Bidwell, L. Cinnamon; Hitt-Laustsen, Sena; Du, Yiping P.; Willcutt, Erik G.

    2009-01-01

    Differences in neural activation during performance on an attentionally demanding Stroop task were examined between 23 young adults with ADHD carefully selected to not be co-morbid for other psychiatric disorders and 23 matched controls. A hybrid blocked/single-trial design allowed for examination of more sustained vs. more transient aspects of…

  2. Neural Signatures of Semantic and Phonemic Fluency in Young and Old Adults

    ERIC Educational Resources Information Center

    Meinzer, Marcus; Flaisch, Tobias; Wilser, Lotte; Eulitz, Carsten; Rockstroh, Brigitte; Conway, Tim; Gonzalez-Rothi, Leslie; Crosson, Bruce

    2009-01-01

    As we age, our ability to select and to produce words changes, yet we know little about the underlying neural substrate of word-finding difficulties in old adults. This study was designed to elucidate changes in specific frontally mediated retrieval processes involved in word-finding difficulties associated with advanced age. We implemented two…

  3. Plastic adult stem cells: will they graduate from the school of hard knocks?

    PubMed

    Alison, Malcolm R; Poulsom, Richard; Otto, William R; Vig, Pamela; Brittan, Mairi; Direkze, Natalie C; Preston, Sean L; Wright, Nicholas A

    2003-02-15

    Notwithstanding the fact that adult bone marrow cell engraftment to epithelial organs seems a somewhat uncommon event, there is no doubt it does occur, and under appropriate conditions of a strong and positive selection pressure these cells will expand clonally and make a significant contribution to tissue replacement. Likewise, bone-marrow-derived cells can be amplified in vitro and differentiated into a multitude of tissues. These in essence are the goals of regenerative medicine using any source of stem cells, be it embryonic or adult. Despite such irrefutable evidence of what is possible, a veritable chorus of detractors of adult stem cell plasticity has emerged, some doubting its very existence, motivated perhaps by more than a little self-interest. The issues that have led to this state of affairs have included the inability to reproduce certain widely quoted data, one case where the apparent transdifferentiation was due to contamination of the donor tissue with haematopoietic cells and, most notoriously, extrapolating from the behaviour of embryonic stem cells to suggest that adult bone marrow cells simply fuse with other cells and adopt their phenotype. While these issues need resolving, slamming this whole new field because not everything is crystal clear is not good science. The fact that a phenomenon is quite rare in no way mitigates against its very existence: asteroid collisions with the Earth are rare, but try telling the dinosaurs they do not occur! When such events do occur (transdifferentiation or collision), they certainly can make an impact.

  4. Post-hatch heat warms adult beaks: irreversible physiological plasticity in Japanese quail

    PubMed Central

    Burness, Gary; Huard, Jacqueline R.; Malcolm, Emily; Tattersall, Glenn J.

    2013-01-01

    Across taxa, the early rearing environment contributes to adult morphological and physiological variation. For example, in birds, environmental temperature plays a key role in shaping bill size and clinal trends across latitudinal/thermal gradients. Such patterns support the role of the bill as a thermal window and in thermal balance. It remains unknown whether bill size and thermal function are reversibly plastic. We raised Japanese quail in warm (30°C) or cold (15°C) environments and then at a common intermediate temperature. We predicted that birds raised in cold temperatures would develop smaller bills than warm-reared individuals, and that regulation of blood flow to the bill in response to changing temperatures would parallel the bill's role in thermal balance. Cold-reared birds developed shorter bills, although bill size exhibited ‘catch-up’ growth once adults were placed at a common temperature. Despite having lived in a common thermal environment as adults, individuals that were initially reared in the warmth had higher bill surface temperatures than cold-reared individuals, particularly under cold conditions. This suggests that blood vessel density and/or the control over blood flow in the bill retained a memory of early thermal ontogeny. We conclude that post-hatch temperature reversibly affects adult bill morphology but irreversibly influences the thermal physiological role of bills and may play an underappreciated role in avian energetics. PMID:23884093

  5. Sox2-mediated regulation of adult neural crest precursors and skin repair.

    PubMed

    Johnston, Adam P W; Naska, Sibel; Jones, Karen; Jinno, Hiroyuki; Kaplan, David R; Miller, Freda D

    2013-01-01

    Nerve-derived neural crest cells are essential for regeneration in certain animals, such as newts. Here, we asked whether they play a similar role during mammalian tissue repair, focusing on Sox2-positive neural crest precursors in skin. In adult skin, Sox2 was expressed in nerve-terminal-associated neural crest precursor cells (NCPCs) around the hair follicle bulge, and following injury was induced in nerve-derived cells, likely dedifferentiated Schwann cell precursors. At later times postinjury, Sox2-positive cells were scattered throughout the regenerating dermis, and lineage tracing showed that these were all neural-crest-derived NCPCs. These Sox2-positive NCPCs were functionally important, since acute deletion of Sox2 prior to injury caused a decrease of NCPCs in the wound and aberrant skin repair. These data demonstrate that Sox2 regulates skin repair, likely by controlling NCPCs, and raise the possibility that nerve-derived NCPCs may play a general role in mammalian tissue repair.

  6. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    SciTech Connect

    Khalifa, Shaden A.M.; Medina, Philippe de; Erlandsson, Anna; El-Seedi, Hesham R.; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-04-11

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

  7. Design and implementation of in vivo imaging of neural injury responses in the adult Drosophila wing.

    PubMed

    Fang, Yanshan; Soares, Lorena; Bonini, Nancy M

    2013-04-01

    Live-imaging technology has markedly advanced in the field of neural injury and axon degeneration; however, studies are still predominantly performed in in vitro settings such as cultured neuronal cells or in model organisms such as Caenorhabditis elegans in which axons lack glial wrappings. We recently developed a new in vivo model for adult-stage neural injury in Drosophila melanogaster, using the highly accessible wing of the animal. Because the Drosophila wing is translucent and dispensable for survival, it allows clear and direct visualization of injury-induced progressive responses of axons and glia highlighted by fluorescent protein (FP) markers in live animals over time. Moreover, unlike previous Drosophila models of neural injury, this procedure does not require dissection of the CNS. Thus, the key preparation steps for in vivo imaging of the neural injury response described in this protocol can be completed within 30 min.

  8. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  9. Presenilin-1 regulates neural progenitor cell differentiation in the adult brain

    PubMed Central

    Gadadhar, Archana; Marr, Robert; Lazarov, Orly

    2011-01-01

    Presenilin-1 (PS1) is the catalytic core of the aspartyl protease γ-secretase. Previous genetic studies using germ-line deletion of PS1 and conditional knockout mice demonstrated that PS1 plays an essential role in neuronal differentiation during neural development, but it remained unclear whether PS1 plays a similar role in neurogenesis in the adult brain. Here we show that neural progenitor cells infected with lentiviral vectors expressing short interfering RNA (siRNA) for the exclusive knockdown of PS1 in the neurogenic microenvironments, exhibit a dramatic enhancement of cell differentiation. Infected cells differentiated into neurons, astrocytes and oligodendrocytes, suggesting that multipotentiality of neural progenitor cells is not affected by reduced levels of PS1. Neurosphere cultures treated with γ-secretase inhibitors exhibit a similar phenotype of enhanced cell differentiation, suggesting that PS1 function in neural progenitor cells is γ-secretase-dependent. Neurospheres infected with lentiviral vectors expressing siRNA for the targeting of PS1 differentiated even in the presence of the proliferation factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), suggesting that PS1 dominates EFG and bFGF signaling pathways. Reduction of PS1 expression in neural progenitor cells was accompanied by a decrease in epidermal growth factor receptor (EGFR) and β-catenin expression level, suggesting that they are downstream essential transducers of PS1 signaling in adult neural progenitor cells. These findings suggest a physiological role for PS1 in adult neurogenesis, and a potential target for the manipulation of neural progenitor cell differentiation. PMID:21325529

  10. Long-term fate of neural precursor cells following transplantation into developing and adult CNS.

    PubMed

    Lepore, A C; Neuhuber, B; Connors, T M; Han, S S W; Liu, Y; Daniels, M P; Rao, M S; Fischer, I

    2006-05-12

    Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can

  11. Neural correlates of letter reversal in children and adults.

    PubMed

    Blackburne, Liwei King; Eddy, Marianna D; Kalra, Priya; Yee, Debbie; Sinha, Pawan; Gabrieli, John D E

    2014-01-01

    Children often make letter reversal errors when first learning to read and write, even for letters whose reversed forms do not appear in normal print. However, the brain basis of such letter reversal in children learning to read is unknown. The present study compared the neuroanatomical correlates (via functional magnetic resonance imaging) and the electrophysiological correlates (via event-related potentials or ERPs) of this phenomenon in children, ages 5-12, relative to young adults. When viewing reversed letters relative to typically oriented letters, adults exhibited widespread occipital, parietal, and temporal lobe activations, including activation in the functionally localized visual word form area (VWFA) in left occipito-temporal cortex. Adults exhibited significantly greater activation than children in all of these regions; children only exhibited such activation in a limited frontal region. Similarly, on the P1 and N170 ERP components, adults exhibited significantly greater differences between typical and reversed letters than children, who failed to exhibit significant differences between typical and reversed letters. These findings indicate that adults distinguish typical and reversed letters in the early stages of specialized brain processing of print, but that children do not recognize this distinction during the early stages of processing. Specialized brain processes responsible for early stages of letter perception that distinguish between typical and reversed letters may develop slowly and remain immature even in older children who no longer produce letter reversals in their writing.

  12. Large-scale live imaging of adult neural stem cells in their endogenous niche.

    PubMed

    Dray, Nicolas; Bedu, Sébastien; Vuillemin, Nelly; Alunni, Alessandro; Coolen, Marion; Krecsmarik, Monika; Supatto, Willy; Beaurepaire, Emmanuel; Bally-Cuif, Laure

    2015-10-15

    Live imaging of adult neural stem cells (aNSCs) in vivo is a technical challenge in the vertebrate brain. Here, we achieve long-term imaging of the adult zebrafish telencephalic neurogenic niche and track a population of >1000 aNSCs over weeks, by taking advantage of fish transparency at near-infrared wavelengths and of intrinsic multiphoton landmarks. This methodology enables us to describe the frequency, distribution and modes of aNSCs divisions across the entire germinal zone of the adult pallium, and to highlight regional differences in these parameters.

  13. Discrimination of poly(vinyl chloride) samples with different plasticizers and prediction of plasticizer contents in poly(vinyl chloride) using near-infrared spectroscopy and neural-network analysis.

    PubMed

    Saeki, Kazumitsu; Funatsu, Kimito; Tanabe, Kazutoshi

    2003-02-01

    In the recycling of poly(vinyl chloride) (PVC), it is required to discriminate every plasticizer for quality control. For this purpose, the near-infrared spectra were measured for 41 kinds of PVC samples with different plasticizers (DINP, DOP, DOA, TOTM and Polyester) and different plasticizer contents (0-49%). A neural-network analysis was applied to the near-infrared spectra pretreated by second-derivative processing. They were discriminated from one another. The neural-network analysis also allowed us to propose a calibration model which predicts the contents of plasticizers in PVC. The correlation coefficient (R) and the root-mean-square error of prediction (RMSEP) for the DINP calibration model were found to be 0.999 and 0.41 wt%, respectively. In comparison, a partial least-squares regression analysis was carried out. The R and RMSEP of the DINP calibration model were calculated to be 0.993 and 1.27 wt%, respectively. It is found that a near-infrared spectra measurement combined with a neural-network analysis is useful for plastic recycling.

  14. Stable learning of functional maps in self-organizing spiking neural networks with continuous synaptic plasticity.

    PubMed

    Srinivasa, Narayan; Jiang, Qin

    2013-01-01

    This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1). This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN) to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through ±180° along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex.

  15. Increased Intraregional Synchronized Neural Activity in Adult Brain After Prolonged Adaptation to High-Altitude Hypoxia: A Resting-State fMRI Study.

    PubMed

    Chen, Ji; Fan, Cunxiu; Li, Jinqiang; Han, Qiaoqing; Lin, Jianzhong; Yang, Tianhe; Zhang, Jiaxing

    2016-03-01

    The human brain is intrinsically plastic such that its functional architecture can be reorganized in response to environmental pressures and physiological changes. However, it remains unclear whether a compensatory modification of spontaneous neural activity occurs in adult brain during prolonged high-altitude (HA) adaptation. In this study, we obtained resting-state functional magnetic resonance (MR) images in 16 adults who have immigrated to Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea level (SL) controls. A validated regional homogeneity (Reho) method was employed to investigate the local synchronization of resting-state functional magnetic resonance imaging (fMRI) signals. Seed connectivity analysis was carried out subsequently. Cognitive and physiological assessments were made and correlated with the image metrics. Compared with SL controls, global mean Reho was significantly increased in HA immigrants as well as a regional increase in the right inferolateral sensorimotor cortex. Furthermore, mean z-Reho value extracted within the inferolateral sensorimotor area showed trend-level significant inverse correlation with memory search reaction time in HA immigrants. These observations, for the first time, provide evidence of adult brain resilience of spontaneous neural activity after long-term HA exposure without inherited and developmental effects. Resting-state fMRI could yield valuable information for central mechanisms underlying respiratory and cognitive compensations in adults during prolonged environmentally hypoxic adaptation, paving the way for future HA-adaptive training.

  16. The plastic fly: the effect of sustained fluctuations in adult food supply on life-history traits.

    PubMed

    van den Heuvel, J; Zandveld, J; Mulder, M; Brakefield, P M; Kirkwood, T B L; Shanley, D P; Zwaan, B J

    2014-11-01

    Many adult traits in Drosophila melanogaster show phenotypic plasticity, and the effects of diet on traits such as lifespan and reproduction are well explored. Although plasticity in response to food is still present in older flies, it is unknown how sustained environmental variation affects life-history traits. Here, we explore how such life-long fluctuations of food supply affect weight and survival in groups of flies and affect weight, survival and reproduction in individual flies. In both experiments, we kept adults on constant high or low food and compared these to flies that experienced fluctuations of food either once or twice a week. For these 'yoyo' groups, the initial food level and the duration of the dietary variation differed during adulthood, creating four 'yoyo' fly groups. In groups of flies, survival and weight were affected by adult food. However, for individuals, survival and reproduction, but not weight, were affected by adult food, indicating that single and group housing of female flies affects life-history trajectories. Remarkably, both the manner and extent to which life-history traits varied in relation to food depended on whether flies initially experienced high or low food after eclosion. We therefore conclude that the expression of life-history traits in adult life is affected not only by adult plasticity, but also by early adult life experiences. This is an important but often overlooked factor in studies of life-history evolution and may explain variation in life-history experiments.

  17. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

    PubMed Central

    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

  18. Plasticity of prospective memory through a familiarization intervention in old adults.

    PubMed

    Zöllig, Jacqueline; Mattli, Florentina; Sutter, Christine; Aurelio, Andrea; Martin, Mike

    2012-01-01

    Younger adults consistently outperform older adults in laboratory prospective memory tasks. This study examines the effectiveness of an intervention that familiarizes older adults with the sequence of ongoing events to compensate their reduced prospective memory performance. We compared performance and electrophysiological measures of an intervention group (N = 20, 69-83 years) receiving a familiarization intervention to an individually matched control group (N = 20). As ongoing activity a 2-back working memory task was administered. Neural correlates were studied using event related potentials (ERPs) and source localization (standardized low-resolution brain electromagnetic tomography). Behavioural data showed faster reaction times in correct prospective trials and fewer prospective false alarms in the familiarization intervention group. ERP analyses displayed differential patterns for the two groups and source localization measures distinctively presented group differences in prospective memory trials with the control group recruiting more resources for a successful prospective memory performance. Together our data support the hypothesis that the familiarity with the sequence of ongoing events increases prospective memory performance and that this might be based on a higher efficiency of attentional monitoring resources and evaluation processes in the intervention group.

  19. Neural correlates of conceptual object priming in young and older adults: An event-related fMRI study

    PubMed Central

    Ballesteros, Soledad; Bischof, Gérard N.; Goh, Joshua O.; Park, Denise C.

    2012-01-01

    In this event-related fMRI study, we investigated age-related differences in brain activity associated with conceptual repetition priming in young and older adults. Participants performed a speeded “living/non-living” classification task with three repetitions of familiar objects. Both young and older adults showed a similar magnitude of behavioral priming to repeated objects and evidencing repetition-related activation reductions in fusiform gyrus, superior occipital, middle and inferior temporal cortex, as well as inferior frontal and insula regions. The neural priming effect in young adults was extensive and continued through both the second and third stimulus repetitions, whereas neural priming in older adults was markedly attenuated and reached floor at the second repetition. In young adults, greater neural priming in multiple brain regions correlated with greater behavioral facilitation whereas in older adults, only activation reduction in the left inferior frontal correlated with faster behavioral responses. These findings provide evidence for altered neural priming in older adults despite preserved behavioral priming, and suggest the possibility that age-invariant behavioral priming is observed as a result of more sustained neural processing of stimuli in older adults which may be a form of compensatory neural activity. PMID:23102512

  20. Neural correlates of conceptual object priming in young and older adults: an event-related functional magnetic resonance imaging study.

    PubMed

    Ballesteros, Soledad; Bischof, Gérard N; Goh, Joshua O; Park, Denise C

    2013-04-01

    In this event-related functional magnetic resonance imaging study, we investigated age-related differences in brain activity associated with conceptual repetition priming in young and older adults. Participants performed a speeded "living/nonliving" classification task with 3 repetitions of familiar objects. Both young and older adults showed a similar magnitude of behavioral priming to repeated objects and evidenced repetition-related activation reductions in fusiform gyrus, superior occipital, middle, and inferior temporal cortex, and inferior frontal and insula regions. The neural priming effect in young adults was extensive and continued through both the second and third stimulus repetitions, and neural priming in older adults was markedly attenuated and reached floor at the second repetition. In young adults, greater neural priming in multiple brain regions correlated with greater behavioral facilitation and in older adults, only activation reduction in the left inferior frontal correlated with faster behavioral responses. These findings provide evidence for altered neural priming in older adults despite preserved behavioral priming, and suggest the possibility that age-invariant behavioral priming is observed as a result of more sustained neural processing of stimuli in older adults which might be a form of compensatory neural activity.

  1. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  2. Neural processing during older adults' comprehension of spoken sentences: age differences in resource allocation and connectivity.

    PubMed

    Peelle, Jonathan E; Troiani, Vanessa; Wingfield, Arthur; Grossman, Murray

    2010-04-01

    Speech comprehension remains largely preserved in older adults despite significant age-related neurophysiological change. However, older adults' performance declines more rapidly than that of young adults when listening conditions are challenging. We investigated the cortical network underlying speech comprehension in healthy aging using short sentences differing in syntactic complexity, with processing demands further manipulated through speech rate. Neural activity was monitored using blood oxygen level-dependent functional magnetic resonance imaging. Comprehension of syntactically complex sentences activated components of a core sentence-processing network in both young and older adults, including the left inferior and middle frontal gyri, left inferior parietal cortex, and left middle temporal gyrus. However, older adults showed reduced recruitment of inferior frontal regions relative to young adults; the individual degree of recruitment predicted accuracy at the more difficult fast speech rate. Older adults also showed increased activity in frontal regions outside the core sentence-processing network, which may have played a compensatory role. Finally, a functional connectivity analysis demonstrated reduced coherence between activated regions in older adults. We conclude that decreased activation of specialized processing regions, and limited ability to coordinate activity between regions, contribute to older adults' difficulty with sentence comprehension under difficult listening conditions.

  3. Stimulation of dendrogenesis and neural maturation in adult mammals.

    PubMed

    Soto-Vázquez, Ramón; Labastida-López, Carlos; Romero-Castello, Samuel; Benítez-King, Gloria; Parra-Cervantes, Patricia

    2016-05-01

    This work is the result of a technical research patent on dendritogenesis and neuronal maturation, in which the existence was determined of patent documents involving the use of melatonin for the treatment of anxiety, obesity and related diseases of the peripheral and CNS. In this study, an analysis of the state of the art in order to collect technical and scientific elements for the drafting of a new patent on the use of the melatonin molecule in stimulating neuronal maturation in dendritogenesis and mammals was conducted in adults. This study is based on an invention related with this novel use of melatonin.

  4. Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science.

    PubMed

    Bryck, Richard L; Fisher, Philip A

    2012-01-01

    Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  5. Adult retinal pigment epithelium cells express neural progenitor properties and the neuronal precursor protein doublecortin.

    PubMed

    Engelhardt, Maren; Bogdahn, Ulrich; Aigner, Ludwig

    2005-04-08

    The adult mammalian retina is devoid of any detectable neurogenesis. However, different cell types have been suggested to potentially act as neural progenitors in the adult mammalian retina in vitro, such as ciliary body (CB), Muller glia, and retinal pigment epithelium (RPE) cells. In rodents and humans, strong evidence for neural stem or progenitor properties exists only for CB-derived cells, but not for other retinal cell types. Here, we provide a comparative analysis of adult rat CB- and RPE-derived cells suggesting that the two cell types share certain neural progenitor properties in vitro. CB and RPE cells expressed neural progenitor markers such as Nestin, Flk-1, Hes1, and Musashi. They proliferated under adherent and neurosphere conditions and showed limited self-renewal. Moreover, they differentiated into neuronal and glial cells based on the expression of differentiation markers such as the young neuronal marker beta-III tubulin and the glial and progenitor markers GFAP and NG2. Expression of beta-III tubulin was found in cells with neuronal and non-neuronal morphology. A subpopulation of RPE- and CB-derived progenitor cells expressed the neurogenesis-specific protein doublecortin (DCX). Interestingly, DCX expression defined a beta-III tubulin-positive CB and RPE fraction with a distinct neuronal morphology. In summary, the data suggest that RPE cells share with CB cells the potential to de-differentiate into a cell type with neural progenitor-like identity. In addition, DCX expression might define the neuronal-differentiating RPE- and CB-derived progenitor population.

  6. 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

    PubMed Central

    Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J.; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario

    2016-01-01

    Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. Conclusions: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical

  7. Dopamine dysregulation syndrome and levodopa-induced dyskinesias in Parkinson disease: common consequences of anomalous forms of neural plasticity.

    PubMed

    Linazasoro, Gurutz

    2009-01-01

    Four to 10% of patients with Parkinson disease and chronically treated with levodopa undergo an addictionlike behavioral disturbance named dopamine dysregulation syndrome (DDS). This article suggests that patients with Parkinson disease could be especially prone to develop DDS due to the dopamine deficiency and the "priming" of neural networks by the chronic use of drugs with a short half-life, such as levodopa. These suggestions are based on the clinical and molecular similarities between levodopa-induced dyskinesias and behavioral alterations seen in DDS and addiction to illegal drugs. Motor and behavioral abnormalities can be seen as the consequence of common mechanisms involving anomalous forms of neural plasticity. These forms affect parts of the cortical-basal ganglia-thalamocortical circuits that are topographically organized to differently modulate emotional and motor functions. Recent evidence using positron emission tomography provides support to this idea. By contrast, molecular data suggest that functional segregation may be lost in addiction, DDS, and dyskinesias. The existence of common pathogenic mechanisms for both phenomena could provide the basis for common therapeutic strategies.

  8. Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

    PubMed Central

    Bennett, James E. M.; Bair, Wyeth

    2015-01-01

    Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli. PMID:26308406

  9. Neural-competent cells of adult human dermis belong to the Schwann lineage.

    PubMed

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-11-11

    Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  10. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    PubMed Central

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G.; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-01-01

    Summary Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread. PMID:25418723

  11. Older adults benefit from music training early in life: biological evidence for long-term training-driven plasticity.

    PubMed

    White-Schwoch, Travis; Woodruff Carr, Kali; Anderson, Samira; Strait, Dana L; Kraus, Nina

    2013-11-06

    Aging results in pervasive declines in nervous system function. In the auditory system, these declines include neural timing delays in response to fast-changing speech elements; this causes older adults to experience difficulty understanding speech, especially in challenging listening environments. These age-related declines are not inevitable, however: older adults with a lifetime of music training do not exhibit neural timing delays. Yet many people play an instrument for a few years without making a lifelong commitment. Here, we examined neural timing in a group of human older adults who had nominal amounts of music training early in life, but who had not played an instrument for decades. We found that a moderate amount (4-14 years) of music training early in life is associated with faster neural timing in response to speech later in life, long after training stopped (>40 years). We suggest that early music training sets the stage for subsequent interactions with sound. These experiences may interact over time to sustain sharpened neural processing in central auditory nuclei well into older age.

  12. Reaction-diffusion-like formalism for plastic neural networks reveals dissipative solitons at criticality

    NASA Astrophysics Data System (ADS)

    Grytskyy, Dmytro; Diesmann, Markus; Helias, Moritz

    2016-06-01

    Self-organized structures in networks with spike-timing dependent synaptic plasticity (STDP) are likely to play a central role for information processing in the brain. In the present study we derive a reaction-diffusion-like formalism for plastic feed-forward networks of nonlinear rate-based model neurons with a correlation sensitive learning rule inspired by and being qualitatively similar to STDP. After obtaining equations that describe the change of the spatial shape of the signal from layer to layer, we derive a criterion for the nonlinearity necessary to obtain stable dynamics for arbitrary input. We classify the possible scenarios of signal evolution and find that close to the transition to the unstable regime metastable solutions appear. The form of these dissipative solitons is determined analytically and the evolution and interaction of several such coexistent objects is investigated.

  13. Self-tuning of neural circuits through short-term synaptic plasticity.

    PubMed

    Sussillo, David; Toyoizumi, Taro; Maass, Wolfgang

    2007-06-01

    Numerous experimental data show that cortical networks of neurons are not silent in the absence of external inputs, but rather maintain a low spontaneous firing activity. This aspect of cortical networks is likely to be important for their computational function, but is hard to reproduce in models of cortical circuits of neurons because the low-activity regime is inherently unstable. Here we show-through theoretical analysis and extensive computer simulations-that short-term synaptic plasticity endows models of cortical circuits with a remarkable stability in the low-activity regime. This short-term plasticity works as a homeostatic mechanism that stabilizes the overall activity level in spite of drastic changes in external inputs and internal circuit properties, while preserving reliable transient responses to signals. The contribution of synaptic dynamics to this stability can be predicted on the basis of general principles from control theory.

  14. Reaction-diffusion-like formalism for plastic neural networks reveals dissipative solitons at criticality.

    PubMed

    Grytskyy, Dmytro; Diesmann, Markus; Helias, Moritz

    2016-06-01

    Self-organized structures in networks with spike-timing dependent synaptic plasticity (STDP) are likely to play a central role for information processing in the brain. In the present study we derive a reaction-diffusion-like formalism for plastic feed-forward networks of nonlinear rate-based model neurons with a correlation sensitive learning rule inspired by and being qualitatively similar to STDP. After obtaining equations that describe the change of the spatial shape of the signal from layer to layer, we derive a criterion for the nonlinearity necessary to obtain stable dynamics for arbitrary input. We classify the possible scenarios of signal evolution and find that close to the transition to the unstable regime metastable solutions appear. The form of these dissipative solitons is determined analytically and the evolution and interaction of several such coexistent objects is investigated.

  15. Anomaly in neural phase coherence accompanies reduced sensorimotor integration in adults who stutter.

    PubMed

    Sengupta, Ranit; Shah, Shalin; Gore, Katie; Loucks, Torrey; Nasir, Sazzad M

    2016-12-01

    Despite advances in our understanding of the human speech system, the neurophysiological basis of stuttering remains largely unknown. Here, it is hypothesized that the speech of adults who stutter (AWS) is susceptible to disruptions in sensorimotor integration caused by neural miscommunication within the speech motor system. Human speech unfolds over rapid timescales and relies on a distributed system of brain regions working in a parallel and synchronized manner, and a breakdown in neural communication between the putative brain regions could increase susceptibility to dysfluency. Using a speech motor adaptation paradigm under altered auditory feedback with simultaneous recording of EEG, the oscillatory cortical dynamics was investigated in stuttering and fluent adults (FA). Auditory feedback perturbation involved the shifting of the formant frequencies of the target vowel sound. Reduced adaptation in response to the feedback error was observed in AWS and was accompanied by differences in EEG spectral powers and anomalies in phase coherence evolving over the course of speech motor training. It is understood that phase coherence possibly captures neural communication within speech motor networks. Thus, the phase coherence network of the two groups exhibited differences involving the EEG frequency bands. These findings in anomalous neural synchrony provide novel evidence for compromised neuronal communication at short time scales within the speech motor network of AWS.

  16. Isolation of neural crest derived chromaffin progenitors from adult adrenal medulla.

    PubMed

    Chung, Kuei-Fang; Sicard, Flavie; Vukicevic, Vladimir; Hermann, Andreas; Storch, Alexander; Huttner, Wieland B; Bornstein, Stefan R; Ehrhart-Bornstein, Monika

    2009-10-01

    Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Unlike the closely-related sympathetic neurons, a subpopulation of proliferation-competent cells exists even in the adult. Here, we describe the isolation, expansion, and in vitro characterization of proliferation-competent progenitor cells from the bovine adrenal medulla. Similar to neurospheres, these cells, when prevented from adherence to the culture dish, grew in spheres, which we named chromospheres. These chromospheres were devoid of mRNA specific for smooth muscle cells (MYH11) or endothelial cells (PECAM1). During sphere formation, markers for differentiated chromaffin cells, such as phenylethanolamine-N-methyl transferase, were downregulated while neural progenitor markers nestin, vimentin, musashi 1, and nerve growth factor receptor, as well as markers of neural crest progenitor cells such as Sox1 and Sox9, were upregulated. Clonal analysis and bromo-2'-deoxyuridine-incorporation analysis demonstrated the self-renewing capacity of chromosphere cells. Differentiation protocols using NGF and BMP4 or dexamethasone induced neuronal or endocrine differentiation, respectively. Electrophysiological analyses of neural cells derived from chromospheres revealed functional properties of mature nerve cells, such as tetrodotoxin-sensitive sodium channels and action potentials. Our study provides evidence that proliferation and differentiation competent chromaffin progenitor cells can be isolated from adult adrenal medulla and that these cells might harbor the potential for the treatment of neurodegenerative diseases, such as Parkinson's disease.

  17. Effects of addictive drugs on adult neural stem/progenitor cells

    PubMed Central

    Xu, Chi; Loh, Horace H.; Law, Ping-Yee

    2015-01-01

    Neural stem/progenitor cells (NSPCs) undergo a series of developmental processes before giving rise to newborn neurons, astrocytes and oligodendrocytes in adult neurogenesis. During the past decade, the role of NSPCs has been highlighted by studies on adult neurogenesis modulated by addictive drugs. It has been proven that these drugs regulate the proliferation, differentiation and survival of adult NSPCs in different manners, which results in the varying consequences of adult neurogenesis. The effects of addictive drugs on NSPCs are exerted via a variety of different mechanisms and pathways, which interact with one another and contribute to the complexity of NSPC regulation. Here, we review the effects of different addictive drugs on NSPCs, and the related experimental methods and paradigms. We also discuss the current understanding of major signaling molecules, especially the putative common mechanisms, underlying such effects. Finally, we review the future directions of research in this area. PMID:26468052

  18. Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat.

    PubMed

    De Riu, Pier Luigi; Russo, Antonella; Pellitteri, Rosalia; Stanzani, Stefania; Tringali, Giovanni; Roccazzello, Anna Maria; De Riu, Giacomo; Marongiu, Patrizia; Mameli, Ombretta

    2008-09-01

    Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of alpha-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.

  19. Cognitive plasticity in older adults: effects of cognitive training and physical exercise.

    PubMed

    Bherer, Louis

    2015-03-01

    Cognitive training, physical activity, and exercise have often been reported to improve cognitive performance in older adults. This paper reviews some seminal and recent studies using these approaches to improve cognition and physical functioning in healthy older adults and in patients suffering from non-neurological chronic medical conditions. Results from cognitive training studies suggest that despite performance improvement in trained tasks, transfer effects appeared very limited. Surprisingly though, computerized dual-task training has been shown to improve balance and postural control in tests of physical functioning, suggesting that broad transfer can sometimes be observed. Physical exercise intervention studies generally found significant and large improvements in physical capacity, in some cognitive domains, and in quality of life. The benefits seem to be equivalent between frail and nonfrail participants. Overall, results reviewed here support the notion that cognitive plasticity for attentional control, as induced by cognitive training or physical activity and exercise, is preserved in late adulthood. Moreover, results of studies with patients at risk of cognitive decline also suggest that cognitive training and exercise interventions are promising nonpharmaceutical tools to help improve cognition in older at-risk individuals.

  20. Neural plasticity and stress induced changes in defense in the rat.

    PubMed

    Adamec, R E; Blundell, J; Collins, A

    2001-12-01

    We investigated the effects of predator stress on behavior and amygdala afferent and efferent neural transmission in rats. Pathways studied were: ventral angular bundle input to the basolateral amygdala; central and basolateral amygdala output to the periaqueductal gray (PAG). Predator stress was 'anxiogenic' in elevated plus maze, light/dark box and acoustic startle tests one week after stress. Lasting changes were also observed in neural transmission. Predator stress appeared to potentiate right and depotentiate left hemisphere afferent amygdala transmission. In contrast, predator stress potentiated amygdala efferent transmission to right and left PAG, depending on the amygdala nucleus stimulated. Paired pulse and intensity series analysis suggests that transmission changes may be postsynaptic or presynaptic, depending on the pathway. Path analysis relating brain and behavioral changes suggests that potentiation and depotentiation in both hemispheres participate jointly in effecting some, but not all, of the behavioral changes produced by predator stress. Potentiation in left hemisphere amygdala afferents and efferents predicts anxiolytic-like effects, while potentiation in the right hemisphere amygdala afferents predicts anxiogenic-like effects. Path analysis also supports the view that changes in different neural systems mediate changes in different behaviors. These findings have their parallel in studies in the cat, but there are species differences.

  1. Spatiotemporal discrimination in neural networks with short-term synaptic plasticity

    NASA Astrophysics Data System (ADS)

    Shlaer, Benjamin; Miller, Paul

    2015-03-01

    Cells in recurrently connected neural networks exhibit bistability, which allows for stimulus information to persist in a circuit even after stimulus offset, i.e. short-term memory. However, such a system does not have enough hysteresis to encode temporal information about the stimuli. The biophysically described phenomenon of synaptic depression decreases synaptic transmission strengths due to increased presynaptic activity. This short-term reduction in synaptic strengths can destabilize attractor states in excitatory recurrent neural networks, causing the network to move along stimulus dependent dynamical trajectories. Such a network can successfully separate amplitudes and durations of stimuli from the number of successive stimuli. Stimulus number, duration and intensity encoding in randomly connected attractor networks with synaptic depression. Front. Comput. Neurosci. 7:59., and so provides a strong candidate network for the encoding of spatiotemporal information. Here we explicitly demonstrate the capability of a recurrent neural network with short-term synaptic depression to discriminate between the temporal sequences in which spatial stimuli are presented.

  2. Plasticity of interstitial cells of cajal: a study in the small intestine of adult Guinea pigs.

    PubMed

    Mei, Feng; Han, Juan; Huang, Yue; Jiang, Zhong-Yong; Xiong, Cheng-Jie; Zhou, De-Shan

    2009-07-01

    Although it is well known that the reduction of interstitial cells of Cajal (ICCs) is associated with several gastrointestinal motility disorders in clinic, it is unknown whether the mature ICCs still have an active plasticity in adult mammals. This study focused on the issues of the reduction of ICCs during Imatinib administration and the recovery of ICCs following drug withdrawal in the small intestine of adult guinea pigs. ICCs were revealed by immunofluorescence on whole mount preparations with anti-Kit, alpha-smooth muscle actin, (alpha-SMA), and 5-bromo-2'-deoxyuridine (BrdU) antibodies. Moreover, the occurrence of apoptosis was also assayed. Imatinib treatment led to a gradual reduction of ICCs in number around the myenteric plexus and deep muscular plexus, which was dependent on the time but no apoptosis of ICCs was detected with the TUNEL method. During Imatinib treatment, some ICC-like cells were double labeled for Kit and alpha-SMA and a few ICC-like cells were only stained with alpha-SMA. When Imatinib was discontinued, the number of ICCs recovered to normal within 32 days. During this time, some proliferating ICCs were demonstrated by double labeling with Kit and BrdU antibodies. Our results indicated that Kit signaling was essential for the maintenance of survival and proliferation of the mature ICCs in the small intestine of adult guinea pigs. Moreover, ICCs might transdifferentiate to a type of alpha-SMA(+) cells, perhaps a phenotype of smooth muscle cells, when there is a loss-of-function of Kit.

  3. Male Courtship Rate Plasticity in the Butterfly Bicyclus anynana Is Controlled by Temperature Experienced during the Pupal and Adult Stages

    PubMed Central

    Bear, Ashley; Monteiro, Antónia

    2013-01-01

    Environmental cues can act to initiate alternative developmental trajectories that result in different adult phenotypes, including behavioral phenotypes. The developmental period when an organism is sensitive to the cue is often described as a critical period. Here we investigated the critical period for temperature-sensitive courtship rate plasticity in the butterfly Bicyclus anynana. We performed a series of temperature-shift experiments in which larvae, pupae, or adults were shifted for blocks of time from one temperature to an alternative temperature, and then we quantified the courtship rate exhibited by adult males. We discovered that the critical period begins during pupal development and extends into adulthood, but temperature experienced during larval development does not affect male courtship rate. This finding allows us to develop hypotheses that address how developmental and physiological factors may have influenced the evolution of behavioral plasticity in this species. PMID:23717531

  4. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.

    PubMed

    Tan, Ji-Wei; Duan, Ting-Ting; Zhou, Qi-Xin; Ding, Ze-Yang; Jing, Liang; Cao, Jun; Wang, Li-Ping; Mao, Rong-Rong; Xu, Lin

    2015-07-01

    Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.

  5. Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray

    PubMed Central

    Ning, You; Huang, Jian-Hua; Xia, Shi-Jin; Bian, Qin; Chen, Yang; Zhang, Xin-Min; Dong, Jing-Cheng; Shen, Zi-Yin

    2013-01-01

    Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia L., on NSC behaviors and the underlying mechanisms. The self-renewal and proliferation of NSC were examined. We detected neuron- and/or astrocyte-specific markers using immunofluorescence and Western blotting, which could evaluate NSC differentiation. Psoralen treatment significantly inhibited neurosphere formation in a dose-dependent manner. Psoralen treatment increased the expression of the astrocyte-specific marker but decreased neuron-specific marker expression. These results suggested that Psoralen was a differentiation inducer in astrocyte. Differential gene expression following Psoralen treatment was screened using DNA microarray and confirmed by quantitative real-time PCR. Our microarray study demonstrated that Psoralen could effectively regulate the specific gene expression profile of NSC. The genes involved in the classification of cellular differentiation, proliferation, and metabolism, the transcription factors belonging to Ets family, and the hedgehog pathway may be closely related to the regulation. PMID:23983781

  6. Repeated morphine treatment alters polysialylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and cell proliferation in the adult rat hippocampus.

    PubMed

    Kahn, Laëtitia; Alonso, Gérard; Normand, Elisabeth; Manzoni, Olivier J

    2005-01-01

    Altered synaptic transmission and plasticity in brain areas involved in reward and learning are thought to underlie the long-lasting effects of addictive drugs. In support of this idea, opiates reduce neurogenesis [A.J. Eisch et al. (2000) Proceedings of the National Academy of Sciences USA, 97, 7579-7584] and enhance long-term potentiation in adult rodent hippocampus [J.M. Harrison et al. (2002) Journal of Neurophysiology, 87, 2464-2470], a key structure of learning and memory processes. Here we studied how repeated morphine treatment and withdrawal affect cell proliferation and neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus. Our data showed a strong reduction of cellular proliferation in morphine-dependent animals (54% of control) that was followed by a rebound increase after 1 week withdrawal and a return to normal after 2 weeks withdrawal. Morphine dependence was also associated with a drastic reduction in the expression levels of the polysialylated form of neural cell adhesion molecule (68% of control), an adhesion molecule expressed by newly generated neurons and involved in cell migration and structural plasticity. Polysialylated neural cell adhesion molecule levels quickly returned to normal following withdrawal. In morphine-dependent rats, we found a significant increase of glutamate decarboxylase-67 mRNA transcription (170% of control) in dentate gyrus granular cells which was followed by a marked rebound decrease after 1 week withdrawal and a return to normal after 4 weeks withdrawal. Together, the results show, for the first time, that, in addition to reducing cell proliferation and neurogenesis, chronic exposure to morphine dramatically alters neuronal phenotypes in the dentate gyrus-CA3 region of the adult rat hippocampus.

  7. Radial glia and neural progenitors in the adult zebrafish central nervous system.

    PubMed

    Than-Trong, Emmanuel; Bally-Cuif, Laure

    2015-08-01

    The adult central nervous system (CNS) of the zebrafish, owing to its enrichment in constitutive neurogenic niches, is becoming an increasingly used model to address fundamental questions pertaining to adult neural stem cell (NSC) biology, adult neurogenesis and neuronal repair. Studies conducted in several CNS territories (notably the telencephalon, retina, midbrain, cerebellum and spinal cord) highlighted the presence, in these niches, of progenitor cells displaying NSC-like characters. While pointing to radial glial cells (RG) as major long-lasting, constitutively active and/or activatable progenitors in most domains, these studies also revealed a high heterogeneity in the progenitor subtypes used at the top of neurogenic hierarchies, including the persistence of neuroepithelial (NE) progenitors in some areas. Likewise, dissecting the molecular pathways underlying RG maintenance and recruitment under physiological conditions and upon repair in the zebrafish model revealed shared processes but also specific cascades triggering or sustaining reparative NSC recruitment. Together, the zebrafish adult brain reveals an extensive complexity of adult NSC niches, properties and control pathways, which extends existing understanding of adult NSC biology and gives access to novel mechanisms of efficient NSC maintenance and recruitment in an adult vertebrate brain.

  8. c-jun is differentially expressed in embryonic and adult neural precursor cells.

    PubMed

    Kawashima, Fumiaki; Saito, Kengo; Kurata, Hirofumi; Maegaki, Yoshihiro; Mori, Tetsuji

    2017-01-16

    c-jun, a major component of AP-1 transcription factor, has a wide variety of functions. In the embryonic brain, c-jun mRNA is abundantly expressed in germinal layers around the ventricles. Although the subventricular zone (SVZ) of the adult brain is a derivative of embryonic germinal layers and contains neural precursor cells (NPCs), the c-jun expression pattern is not clear. To study the function of c-jun in adult neurogenesis, we analyzed c-jun expression in the adult SVZ by immunohistochemistry and compared it with that of the embryonic brain. We found that almost all proliferating embryonic NPCs expressed c-jun, but the number of c-jun immunopositive cells among proliferating adult NPCs was about half. In addition, c-jun was hardly expressed in post-mitotic migrating neurons in the embryonic brain, but the majority of c-jun immunopositive cells were tangentially migrating neuroblasts heading toward the olfactory bulb in the adult brain. In addition, status epilepticus is known to enhance the transient proliferation of adult NPCs, but the c-jun expression pattern was not significantly affected. These expression patterns suggest that c-jun has a pivotal role in the proliferation of embryonic NPCs, but it has also other roles in adult neurogenesis.

  9. Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex.

    PubMed

    Li, Xiao; Yu, Kai; Zhang, Zicong; Sun, Wenjian; Yang, Zhou; Feng, Jingyu; Chen, Xi; Liu, Chun-Hua; Wang, Haitao; Guo, Yi Ping; He, Jufang

    2014-03-01

    Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.

  10. Quiescent adult neural stem cells are exceptionally sensitive to cosmic radiation

    PubMed Central

    Encinas, Juan M.; Vazquez, Marcelo E.; Switzer, Robert C.; Chamberland, Dennis W.; Nick, Harry; Levine, Howard G.; Scarpa, Philip J.; Enikolopov, Grigori; Steindler, Dennis A.

    2012-01-01

    Generation of new neurons in the adult brain, a process that is likely to be essential for learning, memory, and mood regulation, is impaired by radiation. Therefore, radiation exposure might have not only such previously expected consequences as increased probability of developing cancer, but might also impair cognitive function and emotional stability. Radiation exposure is encountered in settings ranging from cancer therapy to space travel; evaluating the neurogenic risks of radiation requires identifying the at-risk populations of stem and progenitor cells in the adult brain. Here we have used a novel reporter mouse line to find that early neural progenitors are selectively affected by conditions simulating the space radiation environment. This is reflected both in a decrease in the number of these progenitors in the neurogenic regions and in an increase in the number of dying cells in these regions. Unexpectedly, we found that quiescent neural stem cells, rather than their rapidly dividing progeny, are most sensitive to radiation. Since these stem cells are responsible for adult neurogenesis, their death would have a profound impact on the production of new neurons in the irradiated adult brain. Our finding raises an important concern about cognitive and emotional risks associated with radiation exposure. PMID:18076878

  11. Resting state neural networks for visual Chinese word processing in Chinese adults and children.

    PubMed

    Li, Ling; Liu, Jiangang; Chen, Feiyan; Feng, Lu; Li, Hong; Tian, Jie; Lee, Kang

    2013-07-01

    This study examined the resting state neural networks for visual Chinese word processing in Chinese children and adults. Both the functional connectivity (FC) and amplitude of low frequency fluctuation (ALFF) approaches were used to analyze the fMRI data collected when Chinese participants were not engaged in any specific explicit tasks. We correlated time series extracted from the visual word form area (VWFA) with those in other regions in the brain. We also performed ALFF analysis in the resting state FC networks. The FC results revealed that, regarding the functionally connected brain regions, there exist similar intrinsically organized resting state networks for visual Chinese word processing in adults and children, suggesting that such networks may already be functional after 3-4 years of informal exposure to reading plus 3-4 years formal schooling. The ALFF results revealed that children appear to recruit more neural resources than adults in generally reading-irrelevant brain regions. Differences between child and adult ALFF results suggest that children's intrinsic word processing network during the resting state, though similar in functional connectivity, is still undergoing development. Further exposure to visual words and experience with reading are needed for children to develop a mature intrinsic network for word processing. The developmental course of the intrinsically organized word processing network may parallel that of the explicit word processing network.

  12. Dynamical Mean-Field Equations for a Neural Network with Spike Timing Dependent Plasticity

    NASA Astrophysics Data System (ADS)

    Mayer, Jörg; Ngo, Hong-Viet V.; Schuster, Heinz Georg

    2012-09-01

    We study the discrete dynamics of a fully connected network of threshold elements interacting via dynamically evolving synapses displaying spike timing dependent plasticity. Dynamical mean-field equations, which become exact in the thermodynamical limit, are derived to study the behavior of the system driven with uncorrelated and correlated Gaussian noise input. We use correlated noise to verify that our model gives account to the fact that correlated noise provides stronger drive for synaptic modification. Further we find that stochastic independent input leads to a noise dependent transition to the coherent state where all neurons fire together, most notably there exists an optimal noise level for the enhancement of synaptic potentiation in our model.

  13. Chaos and Correlated Avalanches in Excitatory Neural Networks with Synaptic Plasticity

    NASA Astrophysics Data System (ADS)

    Pittorino, Fabrizio; Ibáñez-Berganza, Miguel; di Volo, Matteo; Vezzani, Alessandro; Burioni, Raffaella

    2017-03-01

    A collective chaotic phase with power law scaling of activity events is observed in a disordered mean field network of purely excitatory leaky integrate-and-fire neurons with short-term synaptic plasticity. The dynamical phase diagram exhibits two transitions from quasisynchronous and asynchronous regimes to the nontrivial, collective, bursty regime with avalanches. In the homogeneous case without disorder, the system synchronizes and the bursty behavior is reflected into a period doubling transition to chaos for a two dimensional discrete map. Numerical simulations show that the bursty chaotic phase with avalanches exhibits a spontaneous emergence of persistent time correlations and enhanced Kolmogorov complexity. Our analysis reveals a mechanism for the generation of irregular avalanches that emerges from the combination of disorder and deterministic underlying chaotic dynamics.

  14. Chaos and Correlated Avalanches in Excitatory Neural Networks with Synaptic Plasticity.

    PubMed

    Pittorino, Fabrizio; Ibáñez-Berganza, Miguel; di Volo, Matteo; Vezzani, Alessandro; Burioni, Raffaella

    2017-03-03

    A collective chaotic phase with power law scaling of activity events is observed in a disordered mean field network of purely excitatory leaky integrate-and-fire neurons with short-term synaptic plasticity. The dynamical phase diagram exhibits two transitions from quasisynchronous and asynchronous regimes to the nontrivial, collective, bursty regime with avalanches. In the homogeneous case without disorder, the system synchronizes and the bursty behavior is reflected into a period doubling transition to chaos for a two dimensional discrete map. Numerical simulations show that the bursty chaotic phase with avalanches exhibits a spontaneous emergence of persistent time correlations and enhanced Kolmogorov complexity. Our analysis reveals a mechanism for the generation of irregular avalanches that emerges from the combination of disorder and deterministic underlying chaotic dynamics.

  15. Retinal lesions induce fast intrinsic cortical plasticity in adult mouse visual system.

    PubMed

    Smolders, Katrien; Vreysen, Samme; Laramée, Marie-Eve; Cuyvers, Annemie; Hu, Tjing-Tjing; Van Brussel, Leen; Eysel, Ulf T; Nys, Julie; Arckens, Lutgarde

    2016-09-01

    Neuronal activity plays an important role in the development and structural-functional maintenance of the brain as well as in its life-long plastic response to changes in sensory stimulation. We characterized the impact of unilateral 15° laser lesions in the temporal lower visual field of the retina, on visually driven neuronal activity in the afferent visual pathway of adult mice using in situ hybridization for the activity reporter gene zif268. In the first days post-lesion, we detected a discrete zone of reduced zif268 expression in the contralateral hemisphere, spanning the border between the monocular segment of the primary visual cortex (V1) with extrastriate visual area V2M. We could not detect a clear lesion projection zone (LPZ) in areas lateral to V1 whereas medial to V2M, agranular and granular retrosplenial cortex showed decreased zif268 levels over their full extent. All affected areas displayed a return to normal zif268 levels, and this was faster in higher order visual areas than in V1. The lesion did, however, induce a permanent LPZ in the retinorecipient layers of the superior colliculus. We identified a retinotopy-based intrinsic capacity of adult mouse visual cortex to recover from restricted vision loss, with recovery speed reflecting the areal cortical magnification factor. Our observations predict incomplete visual field representations for areas lateral to V1 vs. lack of retinotopic organization for areas medial to V2M. The validation of this mouse model paves the way for future interrogations of cortical region- and cell-type-specific contributions to functional recovery, up to microcircuit level.

  16. Catalog of gene expression in adult neural stem cells and their in vivo microenvironment

    SciTech Connect

    Williams, Cecilia; Wirta, Valtteri; Meletis, Konstantinos; Wikstroem, Lilian; Carlsson, Leif; Frisen, Jonas; Lundeberg, Joakim . E-mail: joakim.lundeberg@biotech.kth.se

    2006-06-10

    Stem cells generally reside in a stem cell microenvironment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique stemness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research.

  17. Hearing loss in older adults affects neural systems supporting speech comprehension.

    PubMed

    Peelle, Jonathan E; Troiani, Vanessa; Grossman, Murray; Wingfield, Arthur

    2011-08-31

    Hearing loss is one of the most common complaints in adults over the age of 60 and a major contributor to difficulties in speech comprehension. To examine the effects of hearing ability on the neural processes supporting spoken language processing in humans, we used functional magnetic resonance imaging to monitor brain activity while older adults with age-normal hearing listened to sentences that varied in their linguistic demands. Individual differences in hearing ability predicted the degree of language-driven neural recruitment during auditory sentence comprehension in bilateral superior temporal gyri (including primary auditory cortex), thalamus, and brainstem. In a second experiment, we examined the relationship of hearing ability to cortical structural integrity using voxel-based morphometry, demonstrating a significant linear relationship between hearing ability and gray matter volume in primary auditory cortex. Together, these results suggest that even moderate declines in peripheral auditory acuity lead to a systematic downregulation of neural activity during the processing of higher-level aspects of speech, and may also contribute to loss of gray matter volume in primary auditory cortex. More generally, these findings support a resource-allocation framework in which individual differences in sensory ability help define the degree to which brain regions are recruited in service of a particular task.

  18. Sexual and seasonal plasticity in the emission of social electric signals. Behavioral approach and neural bases.

    PubMed

    Silva, Ana; Quintana, Laura; Perrone, Rossana; Sierra, Felipe

    2008-01-01

    Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in addition to locomotor displays. Gymnotiformes can modulate the EOD rate to produce signals that participate in different behaviors. We studied the reproductive behavior of Brachyhypopomus pinnicaudatus both in the wild and laboratory settings. During the breeding season, fish produce sexually dimorphic social electric signals (SES): males emit three types of chirps (distinguished by their duration and internal structure), and accelerations, whereas females interrupt their EOD. Since these SES imply EOD frequency modulations, the pacemaker nucleus (PN) is involved in their generation and constitutes the main target organ to explore seasonal and sexual plasticity of the CNS. The PN has two types of neurons, pacemakers and relays, which receive modulatory inputs from pre-pacemaker structures. These neurons show an anisotropic rostro-caudal and dorso-ventral distribution that is paralleled by different field potential waveforms in distinct portions of the PN. In vivo glutamate injections in different areas of the PN provoke different kinds of EOD rate modulations. Ventral injections produce chirp-like responses in breeding males and EOD interruptions in breeding females, whereas dorsal injections provoke EOD frequency rises in both sexes. In the non-breeding season, males and females respond with interruptions when stimulated ventrally and frequency rises when injected dorsally. Our results show that changes of glutamate effects in the PN could explain the seasonal and sexual differences in the generation of SES. By means of behavioral recordings both in the wild and in laboratory settings, and by electrophysiological and pharmacological experiments, we have identified sexual and seasonal plasticity of the CNS and explored its underlying mechanisms.

  19. Human neural stem cell transplantation provides long-term restoration of neuronal plasticity in the irradiated hippocampus.

    PubMed

    Acharya, Munjal M; Rosi, Susanna; Jopson, Timothy; Limoli, Charles L

    2015-01-01

    For the majority of CNS malignancies, radiotherapy provides the best option for forestalling tumor growth, but is frequently associated with debilitating and progressive cognitive dysfunction. Despite the recognition of this serious side effect, satisfactory long-term solutions are not currently available and have prompted our efforts to explore the potential therapeutic efficacy of cranial stem cell transplants. We have demonstrated that intrahippocampal transplantation of human neural stem cells (hNSCs) can provide long-lasting cognitive benefits using an athymic rat model subjected to cranial irradiation. To explore the possible mechanisms underlying the capability of engrafted cells to ameliorate radiation-induced cognitive dysfunction we analyzed the expression patterns of the behaviorally induced activity-regulated cytoskeleton-associated protein (Arc) in the hippocampus at 1 and 8 months postgrafting. While immunohistochemical analyses revealed a small fraction (4.5%) of surviving hNSCs in the irradiated brain that did not express neuronal or astroglial makers, hNSC transplantation impacted the irradiated microenvironment of the host brain by promoting the expression of Arc at both time points. Arc is known to play key roles in the neuronal mechanisms underlying long-term synaptic plasticity and memory and provides a reliable marker for detecting neurons that are actively engaged in spatial and contextual information processing associated with memory consolidation. Cranial irradiation significantly reduced the number of pyramidal (CA1) and granule neurons (DG) expressing behaviorally induced Arc at 1 and 8 months postirradiation. Transplantation of hNSCs restored the expression of plasticity-related Arc in the host brain to control levels. These findings suggest that hNSC transplantation promotes the long-term recovery of host hippocampal neurons and indicates that one mechanism promoting the preservation of cognition after irradiation involves trophic

  20. Effects of bursting dynamic features on the generation of multi-clustered structure of neural network with symmetric spike-timing-dependent plasticity learning rule.

    PubMed

    Liu, Hui; Song, Yongduan; Xue, Fangzheng; Li, Xiumin

    2015-11-01

    In this paper, the generation of multi-clustered structure of self-organized neural network with different neuronal firing patterns, i.e., bursting or spiking, has been investigated. The initially all-to-all-connected spiking neural network or bursting neural network can be self-organized into clustered structure through the symmetric spike-timing-dependent plasticity learning for both bursting and spiking neurons. However, the time consumption of this clustering procedure of the burst-based self-organized neural network (BSON) is much shorter than the spike-based self-organized neural network (SSON). Our results show that the BSON network has more obvious small-world properties, i.e., higher clustering coefficient and smaller shortest path length than the SSON network. Also, the results of larger structure entropy and activity entropy of the BSON network demonstrate that this network has higher topological complexity and dynamical diversity, which benefits for enhancing information transmission of neural circuits. Hence, we conclude that the burst firing can significantly enhance the efficiency of clustering procedure and the emergent clustered structure renders the whole network more synchronous and therefore more sensitive to weak input. This result is further confirmed from its improved performance on stochastic resonance. Therefore, we believe that the multi-clustered neural network which self-organized from the bursting dynamics has high efficiency in information processing.

  1. Effects of bursting dynamic features on the generation of multi-clustered structure of neural network with symmetric spike-timing-dependent plasticity learning rule

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Song, Yongduan; Xue, Fangzheng; Li, Xiumin

    2015-11-01

    In this paper, the generation of multi-clustered structure of self-organized neural network with different neuronal firing patterns, i.e., bursting or spiking, has been investigated. The initially all-to-all-connected spiking neural network or bursting neural network can be self-organized into clustered structure through the symmetric spike-timing-dependent plasticity learning for both bursting and spiking neurons. However, the time consumption of this clustering procedure of the burst-based self-organized neural network (BSON) is much shorter than the spike-based self-organized neural network (SSON). Our results show that the BSON network has more obvious small-world properties, i.e., higher clustering coefficient and smaller shortest path length than the SSON network. Also, the results of larger structure entropy and activity entropy of the BSON network demonstrate that this network has higher topological complexity and dynamical diversity, which benefits for enhancing information transmission of neural circuits. Hence, we conclude that the burst firing can significantly enhance the efficiency of clustering procedure and the emergent clustered structure renders the whole network more synchronous and therefore more sensitive to weak input. This result is further confirmed from its improved performance on stochastic resonance. Therefore, we believe that the multi-clustered neural network which self-organized from the bursting dynamics has high efficiency in information processing.

  2. Effects of bursting dynamic features on the generation of multi-clustered structure of neural network with symmetric spike-timing-dependent plasticity learning rule

    SciTech Connect

    Liu, Hui; Song, Yongduan; Xue, Fangzheng; Li, Xiumin

    2015-11-15

    In this paper, the generation of multi-clustered structure of self-organized neural network with different neuronal firing patterns, i.e., bursting or spiking, has been investigated. The initially all-to-all-connected spiking neural network or bursting neural network can be self-organized into clustered structure through the symmetric spike-timing-dependent plasticity learning for both bursting and spiking neurons. However, the time consumption of this clustering procedure of the burst-based self-organized neural network (BSON) is much shorter than the spike-based self-organized neural network (SSON). Our results show that the BSON network has more obvious small-world properties, i.e., higher clustering coefficient and smaller shortest path length than the SSON network. Also, the results of larger structure entropy and activity entropy of the BSON network demonstrate that this network has higher topological complexity and dynamical diversity, which benefits for enhancing information transmission of neural circuits. Hence, we conclude that the burst firing can significantly enhance the efficiency of clustering procedure and the emergent clustered structure renders the whole network more synchronous and therefore more sensitive to weak input. This result is further confirmed from its improved performance on stochastic resonance. Therefore, we believe that the multi-clustered neural network which self-organized from the bursting dynamics has high efficiency in information processing.

  3. Phthalates in plastic bottled non-alcoholic beverages from China and estimated dietary exposure in adults.

    PubMed

    Yang, Ji-Feng; Yang, Li-Ming; Zheng, Li-Ying; Ying, Guang-Guo; Liu, Cheng-Bin; Luo, Sheng-Lian

    2017-03-01

    Concentrations of six phthalates were determined in 69 plastic bottled non-alcoholic beverages collected from marketplaces in China. Di-n-butyl phthalate (DBP) and di-(2-ethylhexyl)-phthalate (DEHP) were the most detected compounds with frequencies of 100%. Dimethyl phthalate was found less, with a mean frequency of almost 34%. The samples were divided into seven groups. The frequencies of phthalates in these groups ranged from 6.67% to 100%, which indicated that different types of beverages were differently contaminated by phthalates. DEHP contained the highest mean and median concentrations (1.60 ng g(-1) and 0.62 ng g(-1)), followed by DBP (1.34 ng g(-1) and 0.27 ng g(-1)). For DBP, the highest phthalate concentration of 14.3 ng g(-1) was measured. The results of estimated daily intake (EDI) showed that the risk of Chinese adults exposed to these 6 phthalates in beverages examined was lower than the reference doses as suggested by the United States Environmental Protection Agency. The range of EDI values was between 1.77 × 10(-)(4) μg kg-bw(-1) day(-1) and 0.478 μg kg-bw(-1) day(-1).

  4. Magnesium Elevation Promotes Neuronal Differentiation While Suppressing Glial Differentiation of Primary Cultured Adult Mouse Neural Progenitor Cells through ERK/CREB Activation

    PubMed Central

    Liao, Wang; Jiang, Mujun; Li, Mei; Jin, Congli; Xiao, Songhua; Fan, Shengnuo; Fang, Wenli; Zheng, Yuqiu; Liu, Jun

    2017-01-01

    This study aimed to explore the influence of magnesium elevation on fate determination of adult neural progenitor cells (aNPCs) and the underlying mechanism in vitro. Adult neurogenesis, which is the generation of functional neurons from neural precursors, occurs throughout life in restricted anatomical regions in mammals. Magnesium is the fourth most abundant ion in mammals, and its elevation in the brain has been shown to enhance memory and synaptic plasticity in vivo. However, the effects of magnesium on fate determination of aNPCs, which are vital processes in neurogenesis, remain unknown. NPCs isolated from the dentate gyrus of adult C57/BL6 mice were induced to differentiate in a medium with varying magnesium concentrations (0.6, 0.8, and 1.0 mM) and extracellular signal-regulated kinase (ERK) inhibitor PD0325901. The proportion of cells that differentiated into neurons and glial cells was evaluated using immunofluorescence. Quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of β-III tubulin (Tuj1) and glial fibrillary acidic protein (GFAP). The activation of ERK and cAMP response element-binding protein (CREB) was examined by Western blot to reveal the underlying mechanism. Magnesium elevation increased the proportion of Tju1-positive cells and decreased the proportion of GFAP-positive cells. Also, the expression of Tuj1 was upregulated, whereas the expression of GFAP was downregulated. Moreover, magnesium elevation enhanced the activation of both ERK and CREB. Treatment with PD0325901 reversed these effects in a dose-dependent manner. Magnesium elevation promoted neural differentiation while suppressing glial cell differentiation, possibly via ERK-induced CREB activation. PMID:28280456

  5. Language-experience plasticity in neural representation of changes in pitch salience.

    PubMed

    Krishnan, Ananthanarayan; Gandour, Jackson T; Suresh, Chandan H

    2016-04-15

    Neural representation of pitch-relevant information at the brainstem and cortical levels of processing is influenced by language experience. A well-known attribute of pitch is its salience. Brainstem frequency following responses and cortical pitch specific responses, recorded concurrently, were elicited by a pitch salience continuum spanning weak to strong pitch of a dynamic, iterated rippled noise pitch contour-homolog of a Mandarin tone. Our aims were to assess how language experience (Chinese, English) affects i) enhancement of neural activity associated with pitch salience at brainstem and cortical levels, ii) the presence of asymmetry in cortical pitch representation, and iii) patterns of relative changes in magnitude along the pitch salience continuum. Peak latency (Fz: Na, Pb, and Nb) was shorter in the Chinese than the English group across the continuum. Peak-to-peak amplitude (Fz: Na-Pb, Pb-Nb) of the Chinese group grew larger with increasing pitch salience, but an experience-dependent advantage was limited to the Na-Pb component. At temporal sites (T7/T8), the larger amplitude of the Chinese group across the continuum was both limited to the Na-Pb component and the right temporal site. At the brainstem level, F0 magnitude gets larger as you increase pitch salience, and it too reveals Chinese superiority. A direct comparison of cortical and brainstem responses for the Chinese group reveals different patterns of relative changes in magnitude along the pitch salience continuum. Such differences may point to a transformation in pitch processing at the cortical level presumably mediated by local sensory and/or extrasensory influence overlaid on the brainstem output.

  6. Modeling gravity-dependent plasticity of the angular vestibuloocular reflex with a physiologically based neural network.

    PubMed

    Xiang, Yongqing; Yakushin, Sergei B; Cohen, Bernard; Raphan, Theodore

    2006-12-01

    A neural network model was developed to explain the gravity-dependent properties of gain adaptation of the angular vestibuloocular reflex (aVOR). Gain changes are maximal at the head orientation where the gain is adapted and decrease as the head is tilted away from that position and can be described by the sum of gravity-independent and gravity-dependent components. The adaptation process was modeled by modifying the weights and bias values of a three-dimensional physiologically based neural network of canal-otolith-convergent neurons that drive the aVOR. Model parameters were trained using experimental vertical aVOR gain values. The learning rule aimed to reduce the error between eye velocities obtained from experimental gain values and model output in the position of adaptation. Although the model was trained only at specific head positions, the model predicted the experimental data at all head positions in three dimensions. Altering the relative learning rates of the weights and bias improved the model-data fits. Model predictions in three dimensions compared favorably with those of a double-sinusoid function, which is a fit that minimized the mean square error at every head position and served as the standard by which we compared the model predictions. The model supports the hypothesis that gravity-dependent adaptation of the aVOR is realized in three dimensions by a direct otolith input to canal-otolith neurons, whose canal sensitivities are adapted by the visual-vestibular mismatch. The adaptation is tuned by how the weights from otolith input to the canal-otolith-convergent neurons are adapted for a given head orientation.

  7. Residual Neural Processing of Musical Sound Features in Adult Cochlear Implant Users

    PubMed Central

    Timm, Lydia; Vuust, Peter; Brattico, Elvira; Agrawal, Deepashri; Debener, Stefan; Büchner, Andreas; Dengler, Reinhard; Wittfoth, Matthias

    2014-01-01

    Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 min. The presentation of stimuli did not require the participants’ attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients’ age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. Highlights: -Automatic brain responses to musical feature changes

  8. Neural plasticity maintained high by activation of cyclic AMP-dependent protein kinase: an age-independent, general mechanism in cat striate cortex.

    PubMed

    Imamura, K; Kasamatsu, T; Tanaka, S

    2007-06-29

    Adult cats lack ocular dominance plasticity, showing little change in the ocular dominance distribution following monocular deprivation. Ocular dominance plasticity is also lost in kitten visual cortex that has been continuously infused with either catecholaminergic neurotoxin, beta-adrenoreceptor blocker, or inhibitor of cyclic AMP-dependent protein kinase (protein kinase A). Complementarily, in adult cats we showed earlier that pharmacological activation of protein kinase A, albeit partially, restored ocular dominance plasticity. In the present study, we first asked whether, mediated by protein kinase A activation, the same molecular mechanisms could restore ocular dominance plasticity to kitten cortex that once lost the expression of plasticity due to prior pharmacological treatments. Concurrently with monocular deprivation, two kinds of cyclic AMP-related drugs (cholera toxin A-subunit or dibutyryl cyclic AMP) were directly infused in two types of aplastic kitten cortex pretreated with either 6-hydroxydopamine or propranolol. The combined treatment resulted in clear ocular dominance shift to the non-deprived eye, indicating that cortical plasticity was fully restored to aplastic kitten cortex. Next, to directly prove the sensitivity difference in protein kinase A activation between the immature and mature cortex, we compared the thus-obtained data in kittens with the published data derived from adult cats under the comparable experimental paradigm. The extent of ocular dominance changes following monocular deprivation was compared at different drug concentrations in the two preparations: the shifted ocular dominance distribution in aplastic kitten cortex infused with dibutyryl cyclic AMP at the lowest concentration tested and the W-shaped distribution in similarly treated adult cortex at a thousandfold-higher drug concentration that induced nearly maximal changes. We conclude that, irrespective of the animal's age, activation of protein kinase A cascades is a

  9. Embryonic interneurons from the medial, but not the caudal ganglionic eminence trigger ocular dominance plasticity in adult mice.

    PubMed

    Isstas, Marcel; Teichert, Manuel; Bolz, Jürgen; Lehmann, Konrad

    2017-01-01

    The maturation of cortical inhibition provided by parvalbumin-containing basket cells derived from the medial ganglionic eminence (MGE) is a key event in starting the enhanced visual cortical plasticity during the critical period. Although it is generally assumed that a further increase in inhibition closes the critical period again, it was recently shown that embryonic interneurons derived from the MGE can induce an additional, artificial critical period when injected into the visual cortex of young mice. It has, however, remained open whether this effect was indeed specific for MGE-derived cells, and whether critical period-like plasticity could also be induced in fully adult animals. To clarify these issues, we injected explants from either the MGE or the caudal ganglionic eminence (CGE) into the visual cortices of fully adult mice, and performed monocular deprivation 33 days later for 4 days. Animals implanted with MGE cells, but not with CGE cells, showed marked ocular dominance plasticity. Immunohistochemistry confirmed that the injected cells from both sources migrated far in the host cortex, that most developed into neurons producing GABA, and that only cells from the MGE expressed parvalbumin. Thus, our results confirm that the plasticity-inducing effect of embryonic interneurons is specific for cells from the MGE, and is independent of the host animal's age.

  10. Adult neurogenesis, neural stem cells and Alzheimer's disease: developments, limitations, problems and promises.

    PubMed

    Taupin, Philippe

    2009-12-01

    Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease, leading to severe incapacity and death. It is the most common form of dementia among older people. AD is characterized in the brain by amyloid plaques, neurofibrillary tangles, neuronal degeneration, aneuploidy and enhanced neurogenesis and by cognitive, behavioral and physical impairments. Inherited mutations in several genes and genetic, acquired and environmental risk factors have been reported as causes for developing the disease, for which there is currently no cure. Current treatments for AD involve drugs and occupational therapies, and future developments involve early diagnosis and stem cell therapy. In this manuscript, we will review and discuss the recent developments, limitations, problems and promises on AD, particularly related to aneuploidy, adult neurogenesis, neural stem cells (NSCs) and cellular therapy. Though adult neurogenesis may be beneficial for regeneration of the nervous system, it may underly the pathogenesis of AD. Cellular therapy is a promising strategy for AD. Limitations in protocols to establish homogeneous populations of neural progenitor and stem cells and niches for neurogenesis need to be resolved and unlocked, for the full potential of adult NSCs to be realized for therapy.

  11. In vivo imaging of neural reactive plasticity after laser axotomy in cerebellar cortex

    NASA Astrophysics Data System (ADS)

    Allegra Mascaro, A. L.; Sacconi, L.; Maco, B.; Knott, G. W.; Pavone, F. S.

    2014-03-01

    Multi-photon imaging provides valuable insights into the continuous reshaping of neuronal connectivity in live brain. We previously showed that single neuron or even single spine ablation can be achieved by laser-mediated dissection. Furthermore, single axonal branches can be dissected avoiding collateral damage to the adjacent dendrite and the formation of a persistent glial scar. Here, we describe the procedure to address the structural plasticity of cerebellar climbing fibers by combining two-photon in vivo imaging with laser axotomy in a mouse model. This method is a powerful tool to study the basic mechanisms of axonal rewiring after single branch axotomy in vivo. In fact, despite the denervated area being very small, the injured axons consistently reshape the connectivity with surrounding neurons, as indicated by the increase in the turnover of synaptic boutons. In addition, time-lapse imaging reveals the sprouting of new branches from the injured axon. Newly formed branches with varicosities suggest the possible formation of synaptic contacts. Correlative light and electron microscopy revealed that the sprouted branch contains large numbers of vesicles, with varicosities in the close vicinity of Purkinje dendrites.

  12. The Role of Stress Regulation on Neural Plasticity in Pain Chronification

    PubMed Central

    Li, Xiaoyun

    2016-01-01

    Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications. PMID:28053788

  13. Neural plasticity explored by correlative two-photon and electron/SPIM microscopy

    NASA Astrophysics Data System (ADS)

    Allegra Mascaro, A. L.; Silvestri, L.; Costantini, I.; Sacconi, L.; Maco, B.; Knott, G. W.; Pavone, F. S.

    2013-06-01

    Plasticity of the central nervous system is a complex process which involves the remodeling of neuronal processes and synaptic contacts. However, a single imaging technique can reveal only a small part of this complex machinery. To obtain a more complete view, complementary approaches should be combined. Two-photon fluorescence microscopy, combined with multi-photon laser nanosurgery, allow following the real-time dynamics of single neuronal processes in the cerebral cortex of living mice. The structural rearrangement elicited by this highly confined paradigm of injury can be imaged in vivo first, and then the same neuron could be retrieved ex-vivo and characterized in terms of ultrastructural features of the damaged neuronal branch by means of electron microscopy. Afterwards, we describe a method to integrate data from in vivo two-photon fluorescence imaging and ex vivo light sheet microscopy, based on the use of major blood vessels as reference chart. We show how the apical dendritic arbor of a single cortical pyramidal neuron imaged in living mice can be found in the large-scale brain reconstruction obtained with light sheet microscopy. Starting from its apical portion, the whole pyramidal neuron can then be segmented and located in the correct cortical layer. With the correlative approach presented here, researchers will be able to place in a three-dimensional anatomic context the neurons whose dynamics have been observed with high detail in vivo.

  14. Acoustic Emission Source Location in Unidirectional Carbon-Fibre-Reinforced Plastic Plates Using Virtually Trained Artificial Neural Networks

    SciTech Connect

    Caprino, G.; Lopresto, V.; Leone, C.; Papa, I.

    2010-06-02

    Acoustic emission source location in a unidirectional carbon-fibre-reinforced plastic plate was attempted employing Artificial Neural Network (ANN) technology. The acoustic emission events were produced by a lead break, and the response wave received by piezoelectric sensors, type VS150-M resonant at 150 kHz. The waves were detected by a Vallen AMSY4 eight-channel instrumentation. The time of arrival, determined through the conventional threshold crossing technique, was used to measure the dependence of wave velocity on fibre orientation. A simple empirical formula, relying on classical lamination and suggested by wave propagation theory, was able to accurately model the experimental trend. Based on the formula, virtual training and testing data sets were generated for the case of a plate monitored by three transducers, and adopted to select two potentially effective ANN architectures. For final validation, experimental tests were carried out, positioning the source at predetermined points evenly distributed within the plate area. A very satisfactory correlation was found between the actual source locations and the ANN predictions.

  15. Adult Neurogenesis Leads to the Functional Reconstruction of a Telencephalic Neural Circuit

    PubMed Central

    Macedo-Lima, Matheus; Miller, Kimberly E.; Brenowitz, Eliot A.

    2016-01-01

    Seasonally breeding songbirds exhibit pronounced annual changes in song behavior, and in the morphology and physiology of the telencephalic neural circuit underlying production of learned song. Each breeding season, new adult-born neurons are added to the pallial nucleus HVC in response to seasonal changes in steroid hormone levels, and send long axonal projections to their target nucleus, the robust nucleus of the arcopallium (RA). We investigated the role that adult neurogenesis plays in the seasonal reconstruction of this circuit. We labeled newborn HVC neurons with BrdU, and RA-projecting HVC neurons (HVCRA) with retrograde tracer injected in RA of adult male white-crowned sparrows (Zonotrichia leucophrys gambelii) in breeding or nonbreeding conditions. We found that there were many more HVCRA neurons in breeding than nonbreeding birds. Furthermore, we observed that more newborn HVC neurons were back-filled by the tracer in breeding animals. Behaviorally, song structure degraded as the HVC-RA circuit degenerated, and recovered as the circuit regenerated, in close correlation with the number of new HVCRA neurons. These results support the hypothesis that the HVC-RA circuit degenerates in nonbreeding birds, and that newborn neurons reconstruct the circuit in breeding birds, leading to functional recovery of song behavior. SIGNIFICANCE STATEMENT We investigated the role that adult neurogenesis plays in the seasonal reconstruction of a telencephalic neural circuit that controls song behavior in white-crowned sparrows. We showed that nonbreeding birds had a 36%–49% reduction in the number of projection neurons compared with breeding birds, and the regeneration of the circuit in the breeding season is due to the integration of adult-born projection neurons. Additionally, song structure degraded as the circuit degenerated and recovered as the circuit regenerated, in close correlation with new projection neuron number. This study demonstrates that steroid hormones

  16. Plasmid-Based Generation of Induced Neural Stem Cells from Adult Human Fibroblasts

    PubMed Central

    Capetian, Philipp; Azmitia, Luis; Pauly, Martje G.; Krajka, Victor; Stengel, Felix; Bernhardi, Eva-Maria; Klett, Mariana; Meier, Britta; Seibler, Philip; Stanslowsky, Nancy; Moser, Andreas; Knopp, Andreas; Gillessen-Kaesbach, Gabriele; Nikkhah, Guido; Wegner, Florian; Döbrössy, Máté; Klein, Christine

    2016-01-01

    Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV)-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53. We employed a defined neural medium in combination with the neurotrophins bFGF, EGF and FGF4 for cultivation without the addition of small molecules. After reprogramming, cells demonstrated a temporary increase in the expression of endogenous Oct3/4. We obtained induced neural stem cells (iNSC) 30 days after transfection. In contrast to previous results, plasmid vectors as well as a residual expression of reprogramming factors remained detectable in all cell lines. Cells showed a robust differentiation into neuronal (72%) and glial cells (9% astrocytes, 6% oligodendrocytes). Despite the temporary increase of pluripotency-associated Oct3/4 expression during reprogramming, we did not detect pluripotent stem cells or non-neural cells in culture (except occasional residual fibroblasts). Neurons showed electrical activity and functional glutamatergic synapses. Our results demonstrate that reprogramming adult human fibroblasts to iNSC by plasmid vectors and basic neural medium without small molecules is possible and feasible. However, a full set of pluripotency-associated transcription factors may indeed result in the acquisition of a transient (at least partial) pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside the cells at

  17. Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice

    PubMed Central

    Ravinder, Shilpa; Christakis, Dimitri A.

    2016-01-01

    Abstract Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today’s complex technological environment. PMID:27588306

  18. Neural patterns underlying the effect of negative distractors on working memory in older adults.

    PubMed

    Oren, Noga; Ash, Elissa L; Tarrasch, Ricardo; Hendler, Talma; Giladi, Nir; Shapira-Lichter, Irit

    2017-02-03

    Working memory (WM) declines with age. Older adults, however, perform similar to younger adults in WM tasks with negative distractors at low WM load. To clarify the neural basis of this phenomenon, older (n = 28) and younger (n = 24) adults performed an emotional n-back task during an fMRI scan, and activity in task-related regions was examined. Comparing negative with neutral distraction at low WM load, older adults demonstrated shorter reaction times (RT) and reduced activation in frontoparietal regions: bilateral middle frontal gyrus (MFG) and left parietal cortex. They also had greater coherence within the frontoparietal network, as well as greater deactivation of the ventromedial prefrontal cortex and the amygdala. These patterns probably contributed to the older adults' diminished distractibility by negative task-irrelevant stimuli. Since recruitment of control mechanisms was less required, the frontoparietal network was less activated and performance was improved. Faster RT during the negative condition was related to lesser activation of the MFG in both age groups, corroborating the functional significance of this region to WM across the lifespan.

  19. Distinct neural correlates of emotional and cognitive empathy in older adults.

    PubMed

    Moore, Raeanne C; Dev, Sheena I; Jeste, Dilip V; Dziobek, Isabel; Eyler, Lisa T

    2015-04-30

    Empathy is thought to be a mechanism underlying prosocial behavior across the lifespan, yet little is known about how levels of empathy relate to individual differences in brain functioning among older adults. In this exploratory study, we examined the neural correlates of affective and cognitive empathy in older adults. Thirty older adults (M=79 years) underwent fMRI scanning and neuropsychological testing and completed a test of affective and cognitive empathy. Brain response during processing of cognitive and emotional stimuli was measured by fMRI in a priori and task-related regions and was correlated with levels of empathy. Older adults with higher levels of affective empathy showed more deactivation in the amygdala and insula during a working memory task, whereas those with higher cognitive empathy showed greater insula activation during a response inhibition task. Our preliminary findings suggest that brain systems linked to emotional and social processing respond differently among older adults with more or less affective and cognitive empathy. That these relationships can be seen both during affective and non-emotional tasks of "cold" cognitive abilities suggests that empathy may impact social behavior through both emotional and cognitive mechanisms.

  20. Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

    PubMed

    Luo, Yuping; Shan, Ge; Guo, Weixiang; Smrt, Richard D; Johnson, Eric B; Li, Xuekun; Pfeiffer, Rebecca L; Szulwach, Keith E; Duan, Ranhui; Barkho, Basam Z; Li, Wendi; Liu, Changmei; Jin, Peng; Zhao, Xinyu

    2010-04-08

    Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

  1. Cortical plasticity following stripe rearing in the marsupial Monodelphis domestica: neural response properties of V1.

    PubMed

    Dooley, James C; Donaldson, Michaela S; Krubitzer, Leah A

    2017-02-01

    The functional organization of the primary visual area (V1) and the importance of sensory experience in its normal development have been well documented in eutherian mammals. However, very few studies have investigated the response properties of V1 neurons in another large class of mammals, or whether sensory experience plays a role in shaping their response properties. Thus we reared opossums (Monodelphis domestica) in normal and vertically striped cages until they reached adulthood. They were then anesthetized using urethane, and electrophysiological techniques were used to examine neuronal responses to different orientations, spatial and temporal frequencies, and contrast levels. For normal opossums, we observed responses to the temporal and spatial characteristics of the stimulus to be similar to those described in small, nocturnal, eutherian mammals such as rats and mice; neurons in V1 responded maximally to stimuli at 0.09 cycles per degree and 2.12 cycles per second. Unlike other eutherians, but similar to other marsupials investigated, only 40% of the neurons were orientation selective. In stripe-reared animals, neurons were significantly more likely to respond to vertical stimuli at a wider range of spatial frequencies, and were more sensitive to gratings at lower contrast values compared with normal animals. These results are the first to demonstrate experience-dependent plasticity in the visual system of a marsupial species. Thus the ability of cortical neurons to alter their properties based on the dynamics of the visual environment predates the emergence of eutherian mammals and was likely present in our earliest mammalian ancestors.

  2. Brain lateralization and neural plasticity for musical and cognitive abilities in an epileptic musician

    PubMed Central

    Trujillo-Pozo, Isabel; Martín-Monzón, Isabel; Rodríguez-Romero, Rafael

    2013-01-01

    The use of intracarotid propofol procedure (IPP) when assessing musical lateralization has not been reported in literature up to now. This procedure (similar to Wada Test) has provided the opportunity to investigate not only lateralization of language and memory functions on epileptic patients but also offers a functional mapping approach with superior spatial and temporal resolution to analyze the lateralization of musical abilities. Findings in literature suggest that musical training modifies functional and structural brain organization. We studied hemispheric lateralization in a professional musician, a 33 years old woman with refractory left medial temporal lobe (MTL) epilepsy (TLE). A longitudinal neuropsychological study was performed over a period of 21 months. Before epilepsy surgery, musical abilities, language and memory were tested during IPP by means of a novel and exhaustive neuropsychological battery focusing on the processing of music. We used a selection of stimuli to analyze listening, score reading, and tempo discrimination. Our results suggested that IPP is an excellent method to determine not only language, semantic, and episodic memory, but also musical dominance in a professional musician who may be candidate for epilepsy surgery. Neuropsychological testing revealed that right hemisphere's patient is involved in semantic and episodic musical memory processes, whereas her score reading and tempo processing require contribution from both hemispheres. At one-year follow-up, outcome was excellent with respect to seizures and professional skills, meanwhile cognitive abilities improved. These findings indicate that IPP helps to predict who might be at risk for postoperative musical, language, and memory deficits after epilepsy surgery. Our research suggests that musical expertise and epilepsy critically modifies long-term memory processes and induces brain structural and functional plasticity. PMID:24367312

  3. Neural plasticity and treatment-induced recovery of sentence processing in agrammatism

    PubMed Central

    Thompson, Cynthia K.; Ouden, Dirk-Bart den; Bonakdarpour, Borna; Garibaldi, Kyla; Parrish, Todd B.

    2010-01-01

    This study examined patterns of neural activation associated with treatment-induced improvement of complex sentence production (and comprehension) in six individuals with stroke-induced agrammatic aphasia, taking into account possible alterations in blood flow often associated with stroke, including delayed time-to-peak of the hemodynamic response function (HRF) and hypoperfused tissue. Aphasic participants performed an auditory verification fMRI task, processing object cleft, subject cleft, and simple active sentences, prior to and following a course of Treatment of Underlying Forms (TUF; Thompson et al., 2003), a linguistically based approach for treating aphasic sentence deficits, which targeted object relative clause constructions. The patients also were scanned in a long-trials task to examine HRFs, to account for any local deviations resulting from stroke, and perfusion images were obtained to evaluate regions of hypoperfused tissue. Region-of-interest (ROI) analyses were conducted (bilaterally), modeling participant-specific local HRFs in left hemisphere areas activated by 12 healthy age-matched volunteers performing the same task, including the middle and inferior frontal gyri, precentral gyrus, middle and superior temporal gyri, and insula, and additional regions associated with complex syntactic processing, including the posterior perisylvian and superior parietal cortices. Results showed that, despite individual variation in activation differences from pre- to post-treatment scans in the aphasic participants, main-effects analyses revealed a general shift from left superior temporal activation to more posterior temporoparietal areas, bilaterally. Time-to-peak of these responses correlated negatively with blood flow, as measured with perfusion imaging. PMID:20603138

  4. Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice.

    PubMed

    Zhang, Y; Brownstein, A J; Buonora, M; Niikura, K; Ho, A; Correa da Rosa, J; Kreek, M J; Ott, J

    2015-01-29

    Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25 mg/kg/infusion) 2h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available "synaptic plasticity" PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus

  5. Brain Plasticity and Disease: A Matter of Inhibition

    PubMed Central

    Baroncelli, Laura; Braschi, Chiara; Spolidoro, Maria; Begenisic, Tatjana; Maffei, Lamberto; Sale, Alessandro

    2011-01-01

    One major goal in Neuroscience is the development of strategies promoting neural plasticity in the adult central nervous system, when functional recovery from brain disease and injury is limited. New evidence has underscored a pivotal role for cortical inhibitory circuitries in regulating plasticity both during development and in adulthood. This paper summarizes recent findings showing that the inhibition-excitation balance controls adult brain plasticity and is at the core of the pathogenesis of neurodevelopmental disorders like autism, Down syndrome, and Rett syndrome. PMID:21766040

  6. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    PubMed

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration.

  7. A Rare Case of Plastic Bronchitis in an Adult Patient After Cardiopulmonary Bypass.

    PubMed

    Sheikh, Ahmad Y; Ahmadi-Kashani, Mastaneh; Mohindra, Vibha; Friedenberg, Allison; Pramanik, Sharmila B; Ogden, William D

    2016-03-01

    Plastic bronchitis is a rare life-threatening complication observed after cardiopulmonary bypass (CPB). We describe a case of a 54-year-old man in whom a fulminant case of plastic bronchitis developed after coronary artery bypass grafting (CABG) and mitral valve repair. A brief review of the literature is also presented.

  8. Neural Correlates of Dual-Task Walking: Effects of Cognitive versus Motor Interference in Young Adults.

    PubMed

    Beurskens, Rainer; Steinberg, Fabian; Antoniewicz, Franziska; Wolff, Wanja; Granacher, Urs

    2016-01-01

    Walking while concurrently performing cognitive and/or motor interference tasks is the norm rather than the exception during everyday life and there is evidence from behavioral studies that it negatively affects human locomotion. However, there is hardly any information available regarding the underlying neural correlates of single- and dual-task walking. We had 12 young adults (23.8 ± 2.8 years) walk while concurrently performing a cognitive interference (CI) or a motor interference (MI) task. Simultaneously, neural activation in frontal, central, and parietal brain areas was registered using a mobile EEG system. Results showed that the MI task but not the CI task affected walking performance in terms of significantly decreased gait velocity and stride length and significantly increased stride time and tempo-spatial variability. Average activity in alpha and beta frequencies was significantly modulated during both CI and MI walking conditions in frontal and central brain regions, indicating an increased cognitive load during dual-task walking. Our results suggest that impaired motor performance during dual-task walking is mirrored in neural activation patterns of the brain. This finding is in line with established cognitive theories arguing that dual-task situations overstrain cognitive capabilities resulting in motor performance decrements.

  9. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    PubMed

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  10. Growth and differentiation of adult hippocampal arctic ground squirrel neural stem cells.

    PubMed

    Drew, Kelly L; McGee, Rebecca C; Wells, Matthew S; Kelleher-Andersson, Judith A

    2011-01-07

    Arctic ground squirrels (Urocitellus parryii, AGS) are unique in their ability to hibernate with a core body temperature near or below freezing. These animals also resist ischemic injury to the brain in vivo and oxygen-glucose deprivation in vitro. These unique qualities provided the impetus to isolate AGS neurons to examine inherent neuronal characteristics that could account for the capacity of AGS neurons to resist injury and cell death caused by ischemia and extremely cold temperatures. Identifying proteins or gene targets that allow for the distinctive properties of these cells could aid in the discovery of effective therapies for a number of ischemic indications and for the study of cold tolerance. Adult AGS hippocampus contains neural stem cells that continue to proliferate, allowing for easy expansion of these stem cells in culture. We describe here methods by which researchers can utilize these stem cells and differentiated neurons for any number of purposes. By closely following these steps the AGS neural stem cells can be expanded through two passages or more and then differentiated to a culture high in TUJ1-positive neurons (~50%) without utilizing toxic chemicals to minimize the number of dividing cells. Ischemia induces neurogenesis and neurogenesis which proceeds via MEK/ERK and PI3K/Akt survival signaling pathways contributes to ischemia resistance in vivo and in vitro (Kelleher-Anderson, Drew et al., in preparation). Further characterization of these unique neural cells can advance on many fronts, using some or all of these methods.

  11. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish

    PubMed Central

    Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

    2015-01-01

    Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration. PMID:26630262

  12. Altered Neural Processing to Social Exclusion in Young Adult Marijuana Users

    PubMed Central

    Gilman, Jodi M.; Curran, Max T.; Calderon, Vanessa; Schuster, Randi M.; Evins, A. Eden

    2015-01-01

    Previous studies have reported that peer groups are one of the most important predictors of adolescent and young adult marijuana use, and yet the neural correlates of social processing in marijuana users have not yet been studied. In the current study, marijuana-using young adults (n = 20) and non-using controls (n = 22) participated in a neuroimaging social exclusion task called Cyberball, a computerized ball-tossing game in which the participant is excluded from the game after a pre-determined number of ball tosses. Controls, but not marijuana users, demonstrated significant activation in the insula, a region associated with negative emotion, when being excluded from the game. Both groups demonstrated activation of the ventral anterior cingulate cortex (vACC), a region associated with affective monitoring, during peer exclusion. Only the marijuana group showed a correlation between vACC activation and scores on a self-report measure of peer conformity. This study indicates that marijuana users show atypical neural processing of social exclusion, which may be either caused by, or the result of, regular marijuana use. PMID:26977454

  13. Inducible expression of noggin selectively expands neural progenitors in the adult SVZ.

    PubMed

    Morell, M; Tsan, Yao-chang; O'Shea, K Sue

    2015-01-01

    Multipotent, self-renewing stem cells are present throughout the developing nervous system remaining in discrete regions of the adult brain. In the subventricular zone (SVZ) signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, noggin appear to play a critical role in controlling neural stem cell (NSC) behavior. To examine the function of this signaling pathway in the intact nervous system, we developed a transgenic mouse model in which noggin expression can be induced specifically in NSC via a nestin-driven reverse tetracycline-controlled transactivator (rtTA). In adult animals, the induction of noggin expression promotes the proliferation of neural progenitors in the SVZ, and shifts the differentiation of B cells (NSC) from mature astrocytes to transit amplifying C cells and oligodendrocyte precursor cells without depleting the NSC population. Noggin expression significantly increases neuronal and oligodendrocyte differentiation both in vivo and in vitro when NSCs are grown as neurospheres. These results demonstrate that noggin/BMP interactions tightly control cell fate in the SVZ.

  14. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    SciTech Connect

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal . E-mail: iahmad@unmc.edu

    2006-01-13

    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS.

  15. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    SciTech Connect

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  16. The effects of chronic stress on hippocampal adult neurogenesis and dendritic plasticity are reversed by selective MAO-A inhibition.

    PubMed

    Morais, Mónica; Santos, Paulo A R; Mateus-Pinheiro, António; Patrício, Patrícia; Pinto, Luísa; Sousa, Nuno; Pedroso, Pedro; Almeida, Susana; Filipe, Augusto; Bessa, João M

    2014-12-01

    There is accumulating evidence that adult neurogenesis and dendritic plasticity in the hippocampus are neuroplastic phenomena, highly sensitive to the effects of chronic stress and treatment with most classes of antidepressant drugs, being involved in the onset and recovery from depression. However, the effects of antidepressants that act through the selective inhibition of monoamine oxidase subtype A (MAO-A) in these phenomena are still largely unknown. In the present study, adult neurogenesis and neuronal morphology were examined in the hippocampus of rats exposed to chronic mild stress (CMS) and treated with the selective reversible MAO-A inhibitor (RIMA) drug, pirlindole and the selective serotonin reuptake inhibitor (SSRI), fluoxetine. The results provide the first demonstration that selective MAO-A inhibition with pirlindole is able to revert the behavioural effects of stress exposure while promoting hippocampal adult neurogenesis and rescuing the stress-induced dendritic atrophy of granule neurons.

  17. The common and distinct neural bases of affect labeling and reappraisal in healthy adults

    PubMed Central

    Burklund, Lisa J.; Creswell, J. David; Irwin, Michael R.; Lieberman, Matthew D.

    2014-01-01

    Emotion regulation is commonly characterized as involving conscious and intentional attempts to change felt emotions, such as, for example, through reappraisal whereby one intentionally decreases the intensity of one's emotional response to a particular stimulus or situation by reinterpreting it in a less threatening way. However, there is growing evidence and appreciation that some types of emotion regulation are unintentional or incidental, meaning that affective modulation is a consequence but not an explicit goal. For example, affect labeling involves simply verbally labeling the emotional content of an external stimulus or one's own affective responses without an intentional goal of altering emotional responses, yet has been associated with reduced affective responses at the neural and experiential levels. Although both intentional and incidental emotional regulation strategies have been associated with diminished limbic responses and self-reported distress, little previous research has directly compared their underlying neural mechanisms. In this study, we examined the extent to which incidental and intentional emotion regulation, namely, affect labeling and reappraisal, produced common and divergent neural and self-report responses to aversive images relative to an observe-only control condition in a sample of healthy older adults (N = 39). Affect labeling and reappraisal produced common activations in several prefrontal regulatory regions, with affect labeling producing stronger responses in direct comparisons. Affect labeling and reappraisal were also associated with similar decreases in amygdala activity. Finally, affect labeling and reappraisal were associated with correlated reductions in self-reported distress. Together these results point to common neurocognitive mechanisms involved in affect labeling and reappraisal, supporting the idea that intentional and incidental emotion regulation may utilize overlapping neural processes. PMID:24715880

  18. Controlled clinical comparison of plastic and glass bottles of BacT/ALERT FA medium for culturing organisms from blood of adult patients.

    PubMed

    Petti, Cathy A; Mirrett, Stanley; Woods, Christopher W; Reller, L Barth

    2005-04-01

    A new, clear-plastic nonvented aerobic FA bottle, designed to prevent breakage, has been developed for the BacT/ALERT blood culture system. We assessed the new plastic FA bottle by comparing its performance with that of the current glass FA bottle for recovery of microorganisms and time to detection of growth in blood samples obtained for culture from adult patients with suspected bloodstream infections. We conclude that the BacT/ALERT plastic and glass FA bottles are comparable for recovery of microorganisms and that the safety advantage of plastic bottles can be achieved without compromising performance.

  19. Plasticity of connections underlying locomotor recovery after central and/or peripheral lesions in the adult mammals

    PubMed Central

    Rossignol, Serge

    2006-01-01

    This review discusses some aspects of plasticity of connections after spinal injury in adult animal models as a basis for functional recovery of locomotion. After reviewing some pitfalls that must be avoided when claiming functional recovery and the importance of a conceptual framework for the control of locomotion, locomotor recovery after spinal lesions, mainly in cats, is summarized. It is concluded that recovery is partly due to plastic changes within the existing spinal locomotor networks. Locomotor training appears to change the excitability of simple reflex pathways as well as more complex circuitry. The spinal cord possesses an intrinsic capacity to adapt to lesions of central tracts or peripheral nerves but, as a rule, adaptation to lesions entails changes at both spinal and supraspinal levels. A brief summary of the spinal capacity of the rat, mouse and human to express spinal locomotor patterns is given, indicating that the concepts derived mainly from work in the cat extend to other adult mammals. It is hoped that some of the issues presented will help to evaluate how plasticity of existing connections may combine with and potentiate treatments designed to promote regeneration to optimize remaining motor functions. PMID:16939980

  20. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    SciTech Connect

    Boku, Shuken; Nakagawa, Shin; Takamura, Naoki; Kato, Akiko; Takebayashi, Minoru; Hisaoka-Nakashima, Kazue; Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  1. Development and adult phase plasticity of syllable repetitions in the birdsong of captive zebra finches (Taeniopygia guttata).

    PubMed

    Helekar, S A; Espino, G G; Botas, A; Rosenfield, D B

    2003-10-01

    Oscines learn their birdsongs from tutors. The authors found that a small fraction (approximately 7%) of captive male zebra finches (Taeniopygia guttata) produce variant acoustic birdsong profiles consisting of repetitions of single song syllables at high frequencies. Juvenile offspring of nonrepeaters can selectively learn the syntactic rule or habit of repeating syllables from repeaters. Adult tutored syllable repeaters, unlike spontaneous repeaters, undergo a form of song plasticity involving progressive reduction of the mean number and variance of repeated syllables as a function of long-term exposure to nonrepeater songs without altering the number or sequence of syllables within motifs. These findings suggest that aspects of song syntax or temporal frame can be acquired independently of song syllable or spectral content, and plasticity involving restorative alteration of acquired variant temporal frames can occur after the closure of the critical period for song learning.

  2. Brain plasticity and motor practice in cognitive aging.

    PubMed

    Cai, Liuyang; Chan, John S Y; Yan, Jin H; Peng, Kaiping

    2014-01-01

    For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

  3. A comparison of epithelial and neural properties in progenitor cells derived from the adult human ciliary body and brain.

    PubMed

    Moe, Morten C; Kolberg, Rebecca S; Sandberg, Cecilie; Vik-Mo, Einar; Olstorn, Havard; Varghese, Mercy; Langmoen, Iver A; Nicolaissen, Bjørn

    2009-01-01

    Cells isolated from the ciliary body (CB) of the adult human eye possess properties of retinal stem/progenitor cells and can be propagated as spheres in culture. As these cells are isolated from a non-neural epithelium which has neuroepithelial origin, they may have both epithelial and neural lineages. Since it is the properties of neural progenitor cells that are sought after in a future scenario of autotransplantation, we wanted to directly compare human CB spheres with neurospheres derived from the human subventricular zone (SVZ), which is the best characterized neural stem cell niche in the CNS of adults. The CB epithelium was dissected from donor eyes (n = 8). Biopsies from the ventricular wall were harvested during neurosurgery due to epilepsy (n = 7). CB and SVZ tissue were also isolated from Brown Norwegian rats. Dissociated single cells were cultivated in a sphere-promoting medium and passaged every 10-30 days. Fixed spheres were studied by immunohistochemistry, quantitative RT-PCR and scanning/transmission electron microscopy. We found that both CB and SVZ spheres contained a mixed population of cells embedded in extracellular matrix. CB spheres, in contrast to SVZ neurospheres, contained pigmented cells with epithelial morphology that stained for cytokeratins (3/12 + 19), were connected through desmosomes and tight-junctions and produced PEDF. Markers of neural progenitors (nestin, Sox-2, GFAP) were significantly lower expressed in human CB compared to SVZ spheres, and nestin positive cells in the CB spheres also contained pigment. There was higher expression of EGF and TGF-beta receptors in human CB spheres, and a comparative greater activation of the canonical Wnt pathway. These results indicate that adult human CB spheres contain progenitor cells with epithelial properties and limited expression of neural progenitor markers compared to CNS neurospheres. Further studies mapping the regulation between epithelial and neural properties in the adult human

  4. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness.

    PubMed

    Maslin, M R D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J

    2015-10-01

    Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

  5. Plasticity of Attentional Functions in Older Adults after Non-Action Video Game Training: A Randomized Controlled Trial

    PubMed Central

    Mayas, Julia; Parmentier, Fabrice B. R.; Andrés, Pilar; Ballesteros, Soledad

    2014-01-01

    A major goal of recent research in aging has been to examine cognitive plasticity in older adults and its capacity to counteract cognitive decline. The aim of the present study was to investigate whether older adults could benefit from brain training with video games in a cross-modal oddball task designed to assess distraction and alertness. Twenty-seven healthy older adults participated in the study (15 in the experimental group, 12 in the control group. The experimental group received 20 1-hr video game training sessions using a commercially available brain-training package (Lumosity) involving problem solving, mental calculation, working memory and attention tasks. The control group did not practice this package and, instead, attended meetings with the other members of the study several times along the course of the study. Both groups were evaluated before and after the intervention using a cross-modal oddball task measuring alertness and distraction. The results showed a significant reduction of distraction and an increase of alertness in the experimental group and no variation in the control group. These results suggest neurocognitive plasticity in the old human brain as training enhanced cognitive performance on attentional functions. Trial Registration ClinicalTrials.gov NCT02007616 PMID:24647551

  6. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory.

  7. Altered neural activity of magnitude estimation processing in adults with the fragile X premutation.

    PubMed

    Kim, So-Yeon; Hashimoto, Ryu-ichiro; Tassone, Flora; Simon, Tony J; Rivera, Susan M

    2013-12-01

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Expanded CGG trinucleotide repeat (>200 repeats) result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA, and are associated with the risk of developing a neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). While impairments in numerical processing have been well documented in FXS, recent behavioral research suggests that premutation carriers also present with subtle but significant impairments in numerical processing. Using fMRI, the current study examined whether asymptomatic adults with the premutation would show aberrant neural correlates of magnitude estimation processing in the fronto-parietal area. Using a magnitude estimation task, we demonstrated that activity in the intraparietal sulcus and inferior frontal gyrus, associated with magnitude estimation processing, was significantly attenuated in premutation carriers compared to their neurotypical counterparts despite their comparable behavioral performance. Further, multiple regression analysis using CGG repeat size and FMR1 mRNA indicated that increased CGG repeat size is a primary factor for the decreased fronto-parietal activity, suggesting that reduced FMRP, rather than a toxic gain-of-function effect from elevated mRNA, contributes to altered neural activity of magnitude estimation processing in premutation carriers. In conclusion, we provide the first evidence on the aberrant neural correlates of magnitude estimation processing in premutation carriers accounted for by their FMR1 gene expression.

  8. Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence

    PubMed Central

    Reske, Martina; Stewart, Jennifer L.; Flagan, Taru M.; Paulus, Martin P.

    2015-01-01

    Objective Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing. Methods 158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a “risky gains” decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, “risky decisions”). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed. Results There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options. Discussion Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions

  9. Designer Self-Assembling Peptide Nanofiber Scaffolds for Adult Mouse Neural Stem Cell 3-Dimensional Cultures

    PubMed Central

    Gelain, Fabrizio; Bottai, Daniele; Vescovi, Angleo; Zhang, Shuguang

    2006-01-01

    Biomedical researchers have become increasingly aware of the limitations of conventional 2-dimensional tissue cell culture systems, including coated Petri dishes, multi-well plates and slides, to fully address many critical issues in cell biology, cancer biology and neurobiology, such as the 3-D microenvironment, 3-D gradient diffusion, 3-D cell migration and 3-D cell-cell contact interactions. In order to fully understand how cells behave in the 3-D body, it is important to develop a well-controlled 3-D cell culture system where every single ingredient is known. Here we report the development of a 3-D cell culture system using a designer peptide nanofiber scaffold with mouse adult neural stem cells. We attached several functional motifs, including cell adhesion, differentiation and bone marrow homing motifs, to a self-assembling peptide RADA16 (Ac-RADARADARADARADA-COHN2). These functionalized peptides undergo self-assembly into a nanofiber structure similar to Matrigel. During cell culture, the cells were fully embedded in the 3-D environment of the scaffold. Two of the peptide scaffolds containing bone marrow homing motifs significantly enhanced the neural cell survival without extra soluble growth and neurotrophic factors to the routine cell culture media. In these designer scaffolds, the cell populations with β-Tubulin+, GFAP+ and Nestin+ markers are similar to those found in cell populations cultured on Matrigel. The gene expression profiling array experiments showed selective gene expression, possibly involved in neural stem cell adhesion and differentiation. Because the synthetic peptides are intrinsically pure and a number of desired function cellular motifs are easy to incorporate, these designer peptide nanofiber scaffolds provide a promising controlled 3-D culture system for diverse tissue cells, and are useful as well for general molecular and cell biology. PMID:17205123

  10. Electrical coupling can prevent expression of adult-like properties in an embryonic neural circuit.

    PubMed

    Bem, Tiaza; Le Feuvre, Yves; Simmers, John; Meyrand, Pierre

    2002-01-01

    Electrical coupling is widespread in developing nervous systems and plays a major role in circuit formation and patterning of activity. In most reported cases, such coupling between rhythmogenic neurons tends to synchronize and enhance their oscillatory behavior, thereby producing monophasic rhythmic output. However, in many adult networks, such as those responsible for rhythmic motor behavior, oscillatory neurons are linked by synaptic inhibition to produce rhythmic output with multiple phases. The question then arises whether such networks are still able to generate multiphasic output in the early stage of development when electrical coupling is abundant. A suitable model for addressing this issue is the lobster stomatogastric nervous system (STNS). In the adult animal, the STNS consists of three discrete neural networks that are comprised of oscillatory neurons interconnected by reciprocal inhibition. These networks generate three distinct rhythmic motor patterns with large amplitude neuronal oscillations. By contrast, in the embryo the same neuronal population expresses a single multiphasic rhythm with small-amplitude oscillations. Recent findings have revealed that adult-like network properties are already present early in the embryonic system but are masked by an as yet unknown mechanism. Here we use computer simulation to test whether extensive electrical coupling may be involved in masking adult-like properties in the embryonic STNS. Our basic model consists of three different adult-like STNS networks that are built of relaxation oscillators interconnected by reciprocal synaptic inhibition. Individual model cells generate slow membrane potential oscillations without action potentials. The introduction of widespread electrical coupling between members of these networks dampens oscillation amplitudes and, at moderate coupling strengths, may coordinate neuronal activity into a single rhythm with different phases, which is strongly reminiscent of embryonic STNS

  11. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells.

    PubMed

    Regnell, Christine Elisabeth; Hildrestrand, Gunn Annette; Sejersted, Yngve; Medin, Tirill; Moldestad, Olve; Rolseth, Veslemøy; Krokeide, Silje Zandstra; Suganthan, Rajikala; Luna, Luisa; Bjørås, Magnar; Bergersen, Linda H

    2012-09-27

    Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance.

  12. Anxiety and neural responses to infant and adult faces during pregnancy.

    PubMed

    Rutherford, Helena J V; Byrne, Simon P; Austin, Grace M; Lee, Jonathan D; Crowley, Michael J; Mayes, Linda C

    2017-03-06

    Women are vulnerable to anxiety during pregnancy and postpartum. However, little is known about antenatal anxiety and neural processing of infant-relevant information. In this experiment, the N170, P300, and LPP (late positive potential) event-related potentials were measured from 43 pregnant women as they viewed infant and adult faces, which were either neutral or distressed in expression. Mother's self-reported anxiety levels were also assessed. The N170 was comparable across face conditions and was not associated with anxiety. However, our central finding was that greater levels of antenatal anxiety were associated with a larger LPP, but only for neutral infant faces. Results suggest that antenatal anxiety may result in deeper processing of neutral, emotionally ambiguous, infant faces during pregnancy. These findings are discussed in light of other work indicating an interpretive bias toward threat in response to neutral stimuli in anxiety.

  13. H3 and H4 Lysine Acetylation Correlates with Developmental and Experimentally Induced Adult Experience-Dependent Plasticity in the Mouse Visual Cortex

    PubMed Central

    Vierci, Gabriela; Pannunzio, Bruno; Bornia, Natalia; Rossi, Francesco M.

    2016-01-01

    Histone posttranslational modifications play a fundamental role in orchestrating gene expression. In this work, we analyzed the acetylation of H3 and H4 histones (AcH3–AcH4) and its modulation by visual experience in the mouse visual cortex (VC) during normal development and in two experimental conditions that restore juvenile-like plasticity levels in adults (fluoxetine treatment and enriched environment). We found that AcH3–AcH4 declines with age and is upregulated by treatments restoring plasticity in the adult. We also found that visual experience modulates AcH3–AcH4 in young and adult plasticity-restored mice but not in untreated ones. Finally, we showed that the transporter vGAT is downregulated in adult plasticity-restored models. In summary, we identified a dynamic regulation of AcH3–AcH4, which is associated with high plasticity levels and enhanced by visual experience. These data, along with recent ones, indicate H3–H4 acetylation as a central hub in the control of experience-dependent plasticity in the VC. PMID:27891053

  14. Expression of ezrin in subventricular zone neural stem cells and their progeny in adult and developing mice.

    PubMed

    Moon, Younghye; Kim, Joo Yeon; Choi, So Yoen; Cho, Hyo Min; Kim, Hyun; Sun, Woong

    2013-03-01

    Ezrin is a member of the ezrin-radixin-moesin (ERM) family of proteins, which link the cytoskeleton and cell membrane. ERM proteins are involved in pivotal cellular functions including cell-matrix recognition, cell-cell communication, and cell motility. Several recent studies have shown that ERM proteins are expressed in specific cell types of the adult rostral migratory stream (RMS). In this study, we found that ERM proteins are expressed highly in the early postnatal RMS and the ventricular zone of embryonic cerebral cortex, suggesting that these proteins may be expressed by neural progenitors. Furthermore, whereas ezrin previously was found to be expressed exclusively by astrocytes of the adult RMS, we found that ezrin-expressing cells also expressed the markers for indicating neuroblasts in vivo and in vitro, and that ezrin expression by neuroblasts decreases progressively as neuroblasts migrate. Using in vitro differentiation of adult neural stem cells, we found that ezrin is expressed by neural stem cells and their progeny (neuroblasts and astrocytes), but not by oligodendrocytic progeny. Collectively our findings demonstrate that adult neural stem cells and neuroblasts express ezrin and that ezrin may be involved in intracellular actin remodeling.

  15. The Effects of Simulated Stuttering and Prolonged Speech on the Neural Activation Patterns of Stuttering and Nonstuttering Adults

    ERIC Educational Resources Information Center

    De Nil, Luc F.; Beal, Deryk S.; Lafaille, Sophie J.; Kroll, Robert M.; Crawley, Adrian P.; Gracco, Vincent L.

    2008-01-01

    Functional magnetic resonance imaging was used to investigate the neural correlates of passive listening, habitual speech and two modified speech patterns (simulated stuttering and prolonged speech) in stuttering and nonstuttering adults. Within-group comparisons revealed increased right hemisphere biased activation of speech-related regions…

  16. Basic neural processing of sound in adults is influenced by bilingual experience.

    PubMed

    Skoe, Erika; Burakiewicz, Emily; Figueiredo, Michael; Hardin, Margaret

    2017-03-01

    The central auditory nervous system (CANS) undergoes language-dependent tuning to enhance linguistically relevant features of sound. However, less is known about how dual-language exposure affects the CANS. Recent reports indicate that Spanish-English bilingual children and adolescents have larger neural responses to the fundamental frequency (F0) of vowels, as measured by the frequency-following response (FFR), a phase-locked response to sound. Given the cross-language significance of F0, this led us to hypothesize that enhanced neural responses to the F0 are not unique to Spanish-English bilingual children and adolescents but are instead a common feature of a CANS with significant early dual language experience. In support of this hypothesis, we found that early bilingual adults, representing 19 languages, had more robust FFRs to the F0 compared to English-language monolinguals suggesting that bilingual experience imprints on the CANS in a similar fashion regardless of the languages of exposure. Taken together, our results suggest that early exposure to two linguistic sound systems primes the brain to respond to the F0, a basic feature of all speech sounds that signals important indexical information for vowel, talker, and language identification.

  17. Transcription levels of sirtuin family in neural stem cells and brain tissues of adult mice.

    PubMed

    Wang, H F; Li, Q; Feng, R L; Wen, T Q

    2012-09-10

    Neural stem cells (NSCs) has been used as a well-known model to investigate apoptosis, differentiation, maintenance of stem cells status, and therapy of neurological disease. The C17.2 NSCs line was produced after v-myc transformation of neural progenitor from mouse cerebellar cortex. Sirtuin family plays important roles involved in neuronal differentiation, genomic stability, lifespan, cell survival. However, little is known about gene expression variation of sirtuin family in C17.2 NSCs, primary NSCs, and different brain tissues in adult mice. Here, we confirmed that the mRNA expression levels of sirt2, 3, 4, 5, and 7 in E14.5 NSCs were significantly higher than in C17.2 NSCs, whereas that sirt 6 displayed an opposing mode. Moreover, a higher mRNA level of sirtuin family was observed in the adult mouse brain compared to C17.2 NSCs. In addition, histone deacetylase (HDAC) inhibitors nicotinamide and Trichostatin A (TSA) were used to explore differential changes at the transcriptional level of sirtuins. Results indicated that the expression of sirt1, sirt5 and sirt6 was significant downregulated by nicotinamide treatment. Whereas, a significant downregulation in sirt1 and sirt3 and a significant upregulation in sirt2, sirt4, sirt6, and sirt7 were observed in the treatment of TSA. Thus our studies indicate different sirtuin mRNA expression profiles between C17.2 NSCs, E14.5 NSCs and brain tissues, suggesting the transcriptional regulation of sirtuin family could be mediated by different histone acetylation.

  18. Social Interaction Affects Neural Outcomes of Sign Language Learning As a Foreign Language in Adults

    PubMed Central

    Yusa, Noriaki; Kim, Jungho; Koizumi, Masatoshi; Sugiura, Motoaki; Kawashima, Ryuta

    2017-01-01

    Children naturally acquire a language in social contexts where they interact with their caregivers. Indeed, research shows that social interaction facilitates lexical and phonological development at the early stages of child language acquisition. It is not clear, however, whether the relationship between social interaction and learning applies to adult second language acquisition of syntactic rules. Does learning second language syntactic rules through social interactions with a native speaker or without such interactions impact behavior and the brain? The current study aims to answer this question. Adult Japanese participants learned a new foreign language, Japanese sign language (JSL), either through a native deaf signer or via DVDs. Neural correlates of acquiring new linguistic knowledge were investigated using functional magnetic resonance imaging (fMRI). The participants in each group were indistinguishable in terms of their behavioral data after the instruction. The fMRI data, however, revealed significant differences in the neural activities between two groups. Significant activations in the left inferior frontal gyrus (IFG) were found for the participants who learned JSL through interactions with the native signer. In contrast, no cortical activation change in the left IFG was found for the group who experienced the same visual input for the same duration via the DVD presentation. Given that the left IFG is involved in the syntactic processing of language, spoken or signed, learning through social interactions resulted in an fMRI signature typical of native speakers: activation of the left IFG. Thus, broadly speaking, availability of communicative interaction is necessary for second language acquisition and this results in observed changes in the brain.

  19. Impact of Sox9 Dosage and Hes1-mediated Notch Signaling in Controlling the Plasticity of Adult Pancreatic Duct Cells in Mice

    PubMed Central

    Hosokawa, Shinichi; Furuyama, Kenichiro; Horiguchi, Masashi; Aoyama, Yoshiki; Tsuboi, Kunihiko; Sakikubo, Morito; Goto, Toshihiko; Hirata, Koji; Tanabe, Wataru; Nakano, Yasuhiro; Akiyama, Haruhiko; Kageyama, Ryoichiro; Uemoto, Shinji; Kawaguchi, Yoshiya

    2015-01-01

    In the adult pancreas, there has been a long-standing dispute as to whether stem/precursor populations that retain plasticity to differentiate into endocrine or acinar cell types exist in ducts. We previously reported that adult Sox9-expressing duct cells are sufficiently plastic to supply new acinar cells in Sox9-IRES-CreERT2 knock-in mice. In the present study, using Sox9-IRES-CreERT2 knock-in mice as a model, we aimed to analyze how plasticity is controlled in adult ducts. Adult duct cells in these mice express less Sox9 than do wild-type mice but Hes1 equally. Acinar cell differentiation was accelerated by Hes1 inactivation, but suppressed by NICD induction in adult Sox9-expressing cells. Quantitative analyses showed that Sox9 expression increased with the induction of NICD but did not change with Hes1 inactivation, suggesting that Notch regulates Hes1 and Sox9 in parallel. Taken together, these findings suggest that Hes1-mediated Notch activity determines the plasticity of adult pancreatic duct cells and that there may exist a dosage requirement of Sox9 for keeping the duct cell identity in the adult pancreas. In contrast to the extended capability of acinar cell differentiation by Hes1 inactivation, we obtained no evidence of islet neogenesis from Hes1-depleted duct cells in physiological or PDL-induced injured conditions. PMID:25687338

  20. Experience-dependent structural synaptic plasticity in the mammalian brain.

    PubMed

    Holtmaat, Anthony; Svoboda, Karel

    2009-09-01

    Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.

  1. Prentice Award Lecture 2011: Removing the Brakes on Plasticity in the Amblyopic Brain

    PubMed Central

    Levi, Dennis M.

    2012-01-01

    Experience-dependent plasticity is closely linked with the development of sensory function. Beyond this sensitive period, developmental plasticity is actively limited; however, new studies provide growing evidence for plasticity in the adult visual system. The amblyopic visual system is an excellent model for examining the “brakes” that limit recovery of function beyond the critical period. While amblyopia can often be reversed when treated early, conventional treatment is generally not undertaken in older children and adults. However new clinical and experimental studies in both animals and humans provide evidence for neural plasticity beyond the critical period. The results suggest that perceptual learning and video game play may be effective in improving a range of visual performance measures and importantly the improvements may transfer to better visual acuity and stereopsis. These findings, along with the results of new clinical trials, suggest that it might be time to re-consider our notions about neural plasticity in amblyopia. PMID:22581119

  2. A Behavioral Treatment for Traumatic Brain Injury-Associated Visual Dysfunction Based on Adult Cortical Plasticity

    DTIC Science & Technology

    2014-12-01

    phase of eye movements , whereas the superimposed red and green sections are the fast saccadic movements in the left and right direction, respectively...in near vision, as well as in general processing speed, overall attention, cognitive processing, and involuntary eye movement suppression during... movement behaviors, thus supporting that improvements are contributed by brain plasticity following perceptual training. The observed improvement in

  3. Comparing plastic ingestion in juvenile and adult stranded short-tailed shearwaters (Puffinus tenuirostris) in eastern Australia.

    PubMed

    Acampora, Heidi; Schuyler, Qamar A; Townsend, Kathy A; Hardesty, Britta Denise

    2014-01-15

    Numerous species of seabirds have been shown to ingest anthropogenic debris, but few studies have compared ingestion rates between adults and juveniles of the same species. We investigated marine debris ingestion by short-tailed shearwaters (Puffinus tenuirostris) obtained through two stranding events on North Stradbroke Island, Australia in 2010 (n=102; adult) and 2012 (n=27; juveniles). Necropsies were conducted and solid contents found in guts were categorized into type and color. Over 67% of birds ingested anthropogenic debris: 399 pieces of debris were identified. We found no significant relationship between body condition of birds which had ingested anthropogenic debris and those that had not. Juvenile birds were more likely to ingest debris than were adult birds and juveniles ingested significantly more pieces of debris than did adults. Male and female birds ingested similar amounts and weights of debris. To determine if P. tenuirostris actively selects for certain types of debris, we compared ingested debris to samples obtained from boat-based tows. Significant differences were found, suggesting that the birds select for hard plastic, rubber and balloons.

  4. CD44 Transmembrane Receptor and Hyaluronan Regulate Adult Hippocampal Neural Stem Cell Quiescence and Differentiation.

    PubMed

    Su, Weiping; Foster, Scott C; Xing, Rubing; Feistel, Kerstin; Olsen, Reid H J; Acevedo, Summer F; Raber, Jacob; Sherman, Larry S

    2017-03-17

    Adult neurogenesis in the hippocampal subgranular zone (SGZ) is involved in learning and memory throughout life but declines with aging. Mice lacking the CD44 transmembrane receptor for the glycosaminoglycan hyaluronan (HA) demonstrate a number of neurological disturbances including hippocampal memory deficits, implicating CD44 in the processes underlying hippocampal memory encoding, storage, or retrieval. Here, we found that HA and CD44 play important roles in regulating adult neurogenesis, and we provide evidence that HA contributes to age-related reductions in neural stem cell (NSC) expansion and differentiation in the hippocampus. CD44-expressing NSCs isolated from the mouse SGZ are self-renewing and capable of differentiating into neurons, astrocytes, and oligodendrocytes. Mice lacking CD44 demonstrate increases in NSC proliferation in the SGZ. This increased proliferation is also observed in NSCs grown in vitro, suggesting that CD44 functions to regulate NSC proliferation in a cell-autonomous manner. HA is synthesized by NSCs and increases in the SGZ with aging. Treating wild type but not CD44-null NSCs with HA inhibits NSC proliferation. HA digestion in wild type NSC cultures or in the SGZ induces increased NSC proliferation, and CD44-null as well as HA-disrupted wild type NSCs demonstrate delayed neuronal differentiation. HA therefore signals through CD44 to regulate NSC quiescence and differentiation, and HA accumulation in the SGZ may contribute to reductions in neurogenesis that are linked to age-related decline in spatial memory.

  5. Frontal Structural Neural Correlates of Working Memory Performance in Older Adults

    PubMed Central

    Nissim, Nicole R.; O’Shea, Andrew M.; Bryant, Vaughn; Porges, Eric C.; Cohen, Ronald; Woods, Adam J.

    2017-01-01

    Working memory is an executive memory process that allows transitional information to be held and manipulated temporarily in memory stores before being forgotten or encoded into long-term memory. Working memory is necessary for everyday decision-making and problem solving, making it a fundamental process in the daily lives of older adults. Working memory relies heavily on frontal lobe structures and is known to decline with age. The current study aimed to determine the neural correlates of decreased working memory performance in the frontal lobes by comparing cortical thickness and cortical surface area from two demographically matched groups of healthy older adults, free from cognitive impairment, with high versus low N-Back working memory performance (N = 56; average age = 70.29 ± 10.64). High-resolution structural T1-weighted images (1 mm isotropic voxels) were obtained on a 3T Philips MRI scanner. When compared to high performers, low performers exhibited significantly decreased cortical surface area in three frontal lobe regions lateralized to the right hemisphere: medial orbital frontal gyrus, inferior frontal gyrus, and superior frontal gyrus (FDR p < 0.05). There were no significant differences in cortical thickness between groups, a proxy for neurodegenerative tissue loss. Our results suggest that decreases in cortical surface area (a proxy for brain structural integrity) in right frontal regions may underlie age-related decline of working memory function. PMID:28101053

  6. Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

    PubMed Central

    Benninghoff, Jens; Gritti, Angela; Rizzi, Matteo; LaMorte, Giuseppe; Schloesser, Robert J; Schmitt, Angelika; Robel, Stefanie; Genius, Just; Moessner, Rainald; Riederer, Peter; Manji, Husseini K; Grunze, Heinz; Rujescu, Dan; Moeller, Hans-Juergen; Lesch, Klaus-Peter; Vescovi, Angelo Luigi

    2010-01-01

    Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors. PMID:20010549

  7. Serotonin depletion hampers survival and proliferation in neurospheres derived from adult neural stem cells.

    PubMed

    Benninghoff, Jens; Gritti, Angela; Rizzi, Matteo; Lamorte, Giuseppe; Schloesser, Robert J; Schmitt, Angelika; Robel, Stefanie; Genius, Just; Moessner, Rainald; Riederer, Peter; Manji, Husseini K; Grunze, Heinz; Rujescu, Dan; Moeller, Hans-Juergen; Lesch, Klaus-Peter; Vescovi, Angelo Luigi

    2010-03-01

    Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.

  8. KCTD11 expression in medulloblastoma is lower than in adult cerebellum and higher than in neural stem cells.

    PubMed

    Zawlik, Izabela; Zakrzewska, Magdalena; Witusik, Monika; Golanska, Ewa; Kulczycka-Wojdala, Dominika; Szybka, Malgorzata; Piaskowski, Sylwester; Wozniak, Krystyna; Zakrzewski, Krzysztof; Papierz, Wielislaw; Liberski, Pawel P; Rieske, Piotr

    2006-10-01

    Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and the most frequent associated genetic alteration is loss of heterozygosity on chromosome region 7p13. Two genes mapping to this region, KCTD11 (alias REN) and HIC1, have been proposed as involved in MB pathogenesis. We used real-time polymerase chain reaction in 20 tissue samples of primary MB to examine the transcriptional level of the two genes, with reference to two types of controls: adult cerebellum and fetal neural stem cells. A significant reduction of KCTD11 expression relative to adult normal cerebellum was detected in 14 of 20 (70%) of MB samples. Neural stem cells had even lower levels of KCTD11 expression than did MB. HIC1 gene expression was low ( approximately 100 times lower than KCTD11 expression) in MB, and low also in both adult cerebellum and neural stem cells. Hypermethylation of the 5'UTR or the central region of HIC1 (or both) was detected in a significant number of MB samples, as well as in cerebellum and neural stem cells. Our data suggest that KCTD11 may play an important role in MB tumorigenesis, but do not support the role of HIC1 in this tumor development. We argue that recognition of the gene or genes important in MB tumorigenesis depends in part on defining an appropriate control.

  9. Resveratrol: A Potential Hippocampal Plasticity Enhancer

    PubMed Central

    Dias, Gisele Pereira; Cocks, Graham; do Nascimento Bevilaqua, Mário Cesar; Nardi, Antonio Egidio

    2016-01-01

    The search for molecules capable of restoring altered hippocampal plasticity in psychiatric and neurological conditions is one of the most important tasks of modern neuroscience. It is well established that neural plasticity, such as the ability of the postnatal hippocampus to continuously generate newly functional neurons throughout life, a process called adult hippocampal neurogenesis (AHN), can be modulated not only by pharmacological agents, physical exercise, and environmental enrichment, but also by “nutraceutical” agents. In this review we focus on resveratrol, a phenol and phytoalexin found in the skin of grapes and red berries, as well as in nuts. Resveratrol has been reported to have antioxidant and antitumor properties, but its effects as a neural plasticity inducer are still debated. The current review examines recent evidence implicating resveratrol in regulating hippocampal neural plasticity and in mitigating the effects of various disorders and diseases on this important brain structure. Overall, findings show that resveratrol can improve cognition and mood and enhance hippocampal plasticity and AHN; however, some studies report opposite effects, with resveratrol inhibiting aspects of AHN. Therefore, further investigation is needed to resolve these controversies before resveratrol can be established as a safe coadjuvant in preventing and treating neuropsychiatric conditions. PMID:27313836

  10. Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors.

    PubMed

    Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H; Law, Ping-Yee

    2016-01-01

    The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine's inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3-28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1.

  11. Neural Substrates of Verbal Memory Impairments in Adults with T2DM

    PubMed Central

    Yau, Po Lai; Kluger, Alan; Borod, Joan C.; Convit, Antonio

    2014-01-01

    Background Verbal memory impairment is well documented in type 2 diabetes mellitus (T2DM) but to date, the neural substrates remain unclear. The present study evaluated verbal memory and ascertained the degree of frontal and temporal lobe involvement in the anticipated verbal memory impairment among adults with T2DM. Methods Forty-six late middle-aged and elderly adults with T2DM and 50 age-, sex-, and education-matched adults without T2DM underwent medical evaluation, verbal memory assessment, and brain MRI evaluations. Results As anticipated, participants with T2DM had clear verbal memory impairments. Consistent with prior reports, we found volume reductions restricted to the hippocampus. Our diffusion tensor imaging analysis revealed that participants with T2DM had extensive cerebral gray and white matter microstructural abnormalities predominantly in the left hemisphere, with a larger concentration present in the temporal lobe. In contrast, we uncovered mostly non-specific microstructural abnormalities in the absence of tissue loss in the frontal lobe. Of great importance, we present the first evidence among participants with T2DM linking verbal memory impairment and compromised microstructural integrity of the left parahippocampal gyrus, a key memory-relevant structure. Conclusions Our results suggest that the hippocampus and parahippocampal gyrus may be particularly vulnerable to the deleterious effects of T2DM. The parahippocampal gyrus in particular may play a crucial role in the verbal memory impairments frequently reported in T2DM. Future studies should employ methods such as resting state functional magnetic resonance imaging and diffusion tensor imaging tractography to better characterize network connectivity, which may help further characterize the verbal memory impairment frequently reported in T2DM. PMID:24417611

  12. Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

    PubMed Central

    Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H.; Law, Ping-Yee

    2016-01-01

    The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine’s inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3–28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1. PMID:27078155

  13. Hearing Aid-Induced Plasticity in the Auditory System of Older Adults: Evidence from Speech Perception

    ERIC Educational Resources Information Center

    Lavie, Limor; Banai, Karen; Karni, Avi; Attias, Joseph

    2015-01-01

    Purpose: We tested whether using hearing aids can improve unaided performance in speech perception tasks in older adults with hearing impairment. Method: Unaided performance was evaluated in dichotic listening and speech-­in-­noise tests in 47 older adults with hearing impairment; 36 participants in 3 study groups were tested before hearing aid…

  14. Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: neural plasticity or anti-apoptosis?

    PubMed

    Yoon, Kyung Jae; Lee, Yong-Taek; Han, Tai Ryoon

    2011-10-01

    Repetitive transcranial magnetic stimulation (rTMS) has been studied increasingly in recent years to determine whether it has a therapeutic benefit on recovery after stroke. However, the underlying mechanisms of rTMS in stroke recovery remain unclear. Here, we evaluated the effect of rTMS on functional recovery and its underlying mechanism by assessing proteins associated with neural plasticity and anti-apoptosis in the peri-lesional area using a subacute cerebral ischemic rat model. Twenty cerebral ischemic rats were randomly assigned to the rTMS or the sham group at post-op day 4. A total of 3,500 impulses with 10 Hz frequency were applied to ipsilesional cortex over a 2-week period. Functional outcome was measured before (post-op day 4) and after rTMS (post-op day 18). The rTMS group showed more functional improvement on the beam balance test and had stronger Bcl-2 and weaker Bax expression on immunohistochemistry compared with the sham group. The expression of NMDA and MAP-2 showed no significant difference between the two groups. These results suggest that rTMS in subacute cerebral ischemia has a therapeutic effect on functional recovery and is associated with an anti-apoptotic mechanism in the peri-ischemic area rather than with neural plasticity.

  15. Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons

    PubMed Central

    Merianda, Tanuja T.; Jin, Ying

    2017-01-01

    Abstract The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons. PMID:28197547

  16. Tenascin-C and its functions in neuronal plasticity.

    PubMed

    Šekeljić, Vera; Andjus, Pavle R

    2012-06-01

    The extracellular matrix glycoprotein tenascin-C (TN-C), a molecule highly conserved in vertebrates, is widely expressed in neural and non-neural tissue during development, repair processes in the adult organism, and tumorigenesis. In the developing central nervous system (CNS), in different brain regions TN-C is expressed in specific spatial and temporal patterns. In the adult CNS, its expression remains in areas of active neurogenesis and areas that exhibit neuronal plasticity. Understanding of the contribution of this extracellular matrix constituent to the major developmental processes such as cell proliferation and migration, axonal guidance, as well as synaptic plasticity, is derived from studies on TN-C deficient mice. Studies on these mice demonstrated that TN-C plays an important role in neuronal plasticity in the cerebral cortex, hippocampus and cerebellum, possibly by modulating the activity of L-type voltage-dependent Ca(2+) channels.

  17. An fMRI comparison of neural activity associated with recognition of familiar melodies in younger and older adults

    PubMed Central

    Sikka, Ritu; Cuddy, Lola L.; Johnsrude, Ingrid S.; Vanstone, Ashley D.

    2015-01-01

    Several studies of semantic memory in non-musical domains involving recognition of items from long-term memory have shown an age-related shift from the medial temporal lobe structures to the frontal lobe. However, the effects of aging on musical semantic memory remain unexamined. We compared activation associated with recognition of familiar melodies in younger and older adults. Recognition follows successful retrieval from the musical lexicon that comprises a lifetime of learned musical phrases. We used the sparse-sampling technique in fMRI to determine the neural correlates of melody recognition by comparing activation when listening to familiar vs. unfamiliar melodies, and to identify age differences. Recognition-related cortical activation was detected in the right superior temporal, bilateral inferior and superior frontal, left middle orbitofrontal, bilateral precentral, and left supramarginal gyri. Region-of-interest analysis showed greater activation for younger adults in the left superior temporal gyrus and for older adults in the left superior frontal, left angular, and bilateral superior parietal regions. Our study provides powerful evidence for these musical memory networks due to a large sample (N = 40) that includes older adults. This study is the first to investigate the neural basis of melody recognition in older adults and to compare the findings to younger adults. PMID:26500480

  18. Accumulated quiescent neural stem cells in adult hippocampus of the mouse model for the MECP2 duplication syndrome

    PubMed Central

    Chen, Zhifang; Li, Xiao; Zhou, Jingjing; Yuan, Bo; Yu, Bin; Tong, Dali; Cheng, Cheng; Shao, Yinqi; Xia, Shengnan; Zhang, Ran; Lyu, Jingwen; Yu, Xiuya; Dong, Chen; Zhou, Wen-Hao; Qiu, Zilong

    2017-01-01

    Duplications of Methyl CpG binding protein 2 (MECP2) -containing segments lead to the MECP2 duplication syndrome, in which severe autistic symptoms were identified. Whether adult neurogenesis may play a role in pathogenesis of autism and the role of MECP2 on state determination of adult neural stem cells (NSCs) remain largely unclear. Using a MECP2 transgenic (TG) mouse model for the MECP2 duplication syndrome, we found that adult hippocampal quiescent NSCs were significantly accumulated in TG mice comparing to wild type (WT) mice, the neural progenitor cells (NPCs) were reduced and the neuroblasts were increased in adult hippocampi of MECP2 TG mice. Interestingly, we found that parvalbumin (PV) positive interneurons were significantly decreased in MECP2 TG mice, which were critical for determining fates of adult hippocampal NSCs between the quiescence and activation. In summary, we found that MeCP2 plays a critical role in regulating fate determination of adult NSCs. These evidences further suggest that abnormal development of NSCs may play a role in the pathogenesis of the MECP2 duplication syndrome. PMID:28139724

  19. Embryonic Nkx2.1-expressing neural precursor cells contribute to the regional heterogeneity of adult V-SVZ neural stem cells.

    PubMed

    Delgado, Ryan N; Lim, Daniel A

    2015-11-15

    The adult ventricular-subventricular zone (V-SVZ) of the lateral ventricle produces several subtypes of olfactory bulb (OB) interneurons throughout life. Neural stem cells (NSCs) within this zone are heterogeneous, with NSCs located in different regions of the lateral ventricle wall generating distinct OB interneuron subtypes. The regional expression of specific transcription factors appears to correspond to such geographical differences in the developmental potential of V-SVZ NSCs. However, the transcriptional definition and developmental origin of V-SVZ NSC regional identity are not well understood. In this study, we found that a population of NSCs in the ventral region of the V-SVZ expresses the transcription factor Nkx2.1 and is derived from Nkx2.1-expressing (Nkx2.1+) embryonic precursors. To follow the fate of Nkx2.1+ cells and their progeny in vivo, we used mice with an Nkx2.1-CreER "knock-in" allele. Nkx2.1+ V-SVZ NSCs labeled in adult mice generated interneurons for the deep granule cell layer of the OB. Embryonic brain Nkx2.1+ precursors labeled at embryonic day 12.5 gave rise to Nkx2.1+ NSCs of the ventral V-SVZ in postnatal and adult mice. Thus, embryonic Nkx2.1+ neural precursors give rise to a population of Nkx2.1+ NSCs in the ventral V-SVZ where they contribute to the regional heterogeneity of V-SVZ NSCs.

  20. Measurement of neural respiratory drive via parasternal intercostal electromyography in healthy adult subjects.

    PubMed

    MacBean, V; Hughes, C; Nicol, G; Reilly, C C; Rafferty, G F

    2016-11-01

    Neural respiratory drive, quantified by the parasternal intercostal muscle electromyogram (EMGpara), provides a sensitive measure of respiratory system load-capacity balance. Reference values for EMGpara-based measures are lacking and the influence of individual anthropometric characteristics is not known. EMGpara is conventionally expressed as a percentage of that obtained during a maximal inspiratory effort (EMGpara%max), leading to difficulty in applying the technique in subjects unable to reliably perform such manoeuvres. To measure EMGpara in a large, unselected cohort of healthy adult subjects in order to evaluate relevant technical and anthropometric factors. Surface second intercostal space EMGpara was measured during resting breathing and maximal inspiratory efforts in 63 healthy adult subjects, median (IQR) age 31.0 (25.0-47.0) years, 28 males. Detailed anthropometry, spirometry and respiratory muscle strength were also recorded. Median (IQR EMGpara was 4.95 (3.35-6.93) µV, EMGpara%max 4.95 (3.39-8.65)% and neural respiratory drive index (NRDI, the product of EMGpara%max and respiratory rate) was 73.62 (46.41-143.92) %.breath/min. EMGpara increased significantly to 6.28 (4.26-9.93) µV (p  <  0.001) with a mouthpiece, noseclip and pneumotachograph in situ. Median (IQR) EMGpara was higher in female subjects (5.79 (4.42-7.98) µV versus 3.56 (2.81-5.35) µV, p  =  0.003); after controlling for sex neither EMGpara, EMGpara%max or NRDI were significantly related to anthropometrics, age or respiratory muscle strength. In subjects undergoing repeat measurements within the same testing session (n  =  48) or on a separate occasion (n  =  19) similar repeatability was observed for both EMGpara and EMGpara%max. EMGpara is higher in female subjects than males, without influence of other anthropometric characteristics. Reference values are provided for EMGpara-derived measures. Expressing EMGpara as a percentage of maximum confers no

  1. Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice.

    PubMed

    Blanchard, Julie; Chohan, Muhammad Omar; Li, Bin; Liu, Fei; Iqbal, Khalid; Grundke-Iqbal, Inge

    2010-01-01

    A therapeutic strategy against cognitive disorders like Alzheimer's disease is to take advantage of the regenerative ability of the brain and the properties of neurotrophic factors to shift the balance from neurodegeneration to neurogenesis and neuronal plasticity. Although the ciliary neurotrophic factor (CNTF) has some of the required neuroprotective characteristics, its clinical use, due to its side effects, i.e., anorexia, skeletal muscle loss, hyperalgesia, cramps, and muscle pain, has not materialized. In the present study, we report that Peptide 6c (GDDL) that corresponds to CNTF amino acid residues 147-150, enhances the dentate gyrus neurogenesis and neuronal plasticity, and improves cognition without weight loss or any other apparent side effects in mice. Normal adult C57Bl6 mice received subcutaneous implants of extended release depot pellets containing vehicle or Peptide 6c for 30 days of continuous dosing. Dentate gyrus neurogenesis was assessed by stereological analysis of cells expressing neuronal markers, doublecortin and NeuN, and BrdU uptake. We found that Peptide 6c significantly increased early neuronal commitment, differentiation, and survival of newborn progenitor cells. These newborn neurons were functionally integrated into the hippocampal network, since basal expression of c-fos was enhanced and neuronal plasticity was increased, as reflected by higher expression of MAP2a,b and synaptophysin. Consequently, Peptide 6c treatment improved encoding of hippocampal-dependent information in a spatial reference memory task in mice. Overall, these findings demonstrated the therapeutic potential of Peptide 6c for regeneration of the brain and improvement of cognition.

  2. Neuronal and Cognitive Plasticity: A Neurocognitive Framework for Ameliorating Cognitive Aging

    PubMed Central

    Greenwood, Pamela M.; Parasuraman, Raja

    2010-01-01

    What is the neurocognitive basis for the considerable individual differences observed in functioning of the adult mind and brain late in life? We review the evidence that in healthy old age the brain remains capable of both neuronal and cognitive plasticity, including in response to environmental and experiential factors. Neuronal plasticity (e.g., neurogenesis, synaptogenesis, cortical re-organization) refers to neuron-level changes that can be stimulated by experience. Cognitive plasticity (e.g., increased dependence on executive function) refers to adaptive changes in patterns of cognition related to brain activity. We hypothesize that successful cognitive aging requires interactions between these two forms of plasticity. Mechanisms of neural plasticity underpin cognitive plasticity and in turn, neural plasticity is stimulated by cognitive plasticity. We examine support for this hypothesis by considering evidence that neural plasticity is stimulated by learning and novelty and enhanced by both dietary manipulations (low-fat, dietary restriction) and aerobic exercise. We also examine evidence that cognitive plasticity is affected by education and training. This is a testable hypothesis which could be assessed in humans in randomized trials comparing separate and combined effects of cognitive training, exercise, and diet on measures of cognitive and brain integrity. Greater understanding of the factors influencing the course of cognitive aging and of the mechanisms underlying those factors could provide information on which people could base choices that improve their ability to age successfully. PMID:21151819

  3. Neuronal and cognitive plasticity: a neurocognitive framework for ameliorating cognitive aging.

    PubMed

    Greenwood, Pamela M; Parasuraman, Raja

    2010-01-01

    What is the neurocognitive basis for the considerable individual differences observed in functioning of the adult mind and brain late in life? We review the evidence that in healthy old age the brain remains capable of both neuronal and cognitive plasticity, including in response to environmental and experiential factors. Neuronal plasticity (e.g., neurogenesis, synaptogenesis, cortical re-organization) refers to neuron-level changes that can be stimulated by experience. Cognitive plasticity (e.g., increased dependence on executive function) refers to adaptive changes in patterns of cognition related to brain activity. We hypothesize that successful cognitive aging requires interactions between these two forms of plasticity. Mechanisms of neural plasticity underpin cognitive plasticity and in turn, neural plasticity is stimulated by cognitive plasticity. We examine support for this hypothesis by considering evidence that neural plasticity is stimulated by learning and novelty and enhanced by both dietary manipulations (low-fat, dietary restriction) and aerobic exercise. We also examine evidence that cognitive plasticity is affected by education and training. This is a testable hypothesis which could be assessed in humans in randomized trials comparing separate and combined effects of cognitive training, exercise, and diet on measures of cognitive and brain integrity. Greater understanding of the factors influencing the course of cognitive aging and of the mechanisms underlying those factors could provide information on which people could base choices that improve their ability to age successfully.

  4. The effect of substrate stiffness on adult neural stem cell behavior.

    PubMed

    Leipzig, Nic D; Shoichet, Molly S

    2009-12-01

    Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal and differentiation. In order to better understand the contribution of substrate stiffness to neural stem/progenitor cell (NSPC) differentiation and proliferation, a photopolymerizable methacrylamide chitosan (MAC) biomaterial was developed. Photopolymerizable MAC is particularly compelling for the study of the central nervous system stem cell niche because Young's elastic modulus (E(Y)) can be tuned from less than 1 kPa to greater than 30 kPa. Additionally, the numerous free amine functional groups enable inclusion of biochemical signaling molecules that, together with the mechanical environment, influence cell behavior. Herein, NSPCs proliferated on MAC substrates with Young's elastic moduli below 10 kPa and exhibited maximal proliferation on 3.5 kPa surfaces. Neuronal differentiation was favored on the soft est surfaces with E(Y) < 1 kPa as confirmed by both immunohistochemistry and qRT-PCR. Oligodendrocyte differentiation was favored on stiffer scaffolds (> 7 kPa); however, myelin oligodendrocyte glycoprotein (MOG) gene expression suggested that oligodendrocyte maturation and myelination was best on < 1 kPa scaffolds where more mature neurons were present. Astrocyte differentiation was only observed on < 1 and 3.5 kPa surfaces and represented less than 2% of the total cell population. This work demonstrates the importance of substrate stiffness to the proliferation and differentiation of adult NSPCs and highlights the importance of mechanical properties to the success of scaffolds designed to engineer central nervous system tissue.

  5. The relationship between aerobic fitness and neural oscillations during visuo-spatial attention in young adults.

    PubMed

    Wang, Chun-Hao; Liang, Wei-Kuang; Tseng, Philip; Muggleton, Neil G; Juan, Chi-Hung; Tsai, Chia-Liang

    2015-04-01

    While the cognitive benefits of aerobic fitness have been widely investigated, current findings in young adults remain unclear. Specifically, little is known about how these effects are reflected in the time-frequency domain. This study thus assessed the relationship between aerobic fitness and neural oscillations during visuo-spatial attention. A between-subjects design that included 20 participants with higher aerobic fitness (age = 21.95 ± 2.24 years; VO2max = 58.98 ± 6.94 ml/kg/min) and 20 age- and gender-matched lower aerobic fitness participants (age = 23.25 ± 2.07 years; VO2max = 35.87 ± 3.41 ml/kg/min) was used to examine the fitness-related differences in performance and neuroelectric indexes during a Posner visuo-spatial attention paradigm. The results demonstrated that high-fitness participants, in comparison with their low-fitness counterparts, showed faster reaction times as well as greater modulation of oscillatory theta and beta power during target processing, regardless of cue types. Moreover, the neurocognitive correlation showed that higher theta power was related to better task performance. Collectively, these findings suggest that aerobic fitness is associated with general enhanced attentional control in relation to visuo-spatial processing, as evidenced through greater motor preparation and in particular the up-regulation of attentional processing in healthy young adults. The present study may contribute to current knowledge by revealing the relationship between aerobic fitness and modulation of brain oscillations.

  6. In Vivo Tumorigenesis Was Observed after Injection of In Vitro Expanded Neural Crest Stem Cells Isolated from Adult Bone Marrow

    PubMed Central

    Neirinckx, Virginie; Hennuy, Benoit; Swingland, James T.; Laudet, Emerence; Sommer, Lukas; Shakova, Olga; Bours, Vincent; Rogister, Bernard

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. PMID:23071568

  7. Effects of ECM protein micropatterns on the migration and differentiation of adult neural stem cells.

    PubMed

    Joo, Sunghoon; Kim, Joo Yeon; Lee, Eunsoo; Hong, Nari; Sun, Woong; Nam, Yoonkey

    2015-08-12

    The migration and differentiation of adult neural stem cells (aNSCs) are believed to be strongly influenced by the spatial distribution of extracellular matrix (ECM) proteins in the stem cell niche. In vitro culture platform, which involves the specific spatial distribution of ECM protein, could offer novel tools for better understanding of aNSC behavior in the spatial pattern of ECM proteins. In this work, we applied soft-lithographic technique to design simple and reproducible laminin (LN)-polylysine cell culture substrates and investigated how aNSCs respond to the various spatial distribution of laminin, one of ECM proteins enriched in the aNSC niche. We found that aNSC preferred to migrate and attach to LN stripes, and aNSC-derived neurons and astrocytes showed significant difference in motility towards LN stripes. By changing the spacing of LN stripes, we were able to control the alignment of neurons and astrocytes. To the best of our knowledge, this is the first time to investigate the differential cellular responses of aNSCs on ECM protein (LN) and cell adhesive synthetic polymer (PDL) using surface micropatterns. Our findings would provide a deeper understanding in astrocyte-neuron interactions as well as ECM-stem cell interactions.

  8. MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks.

    PubMed

    Lippi, Giordano; Fernandes, Catarina C; Ewell, Laura A; John, Danielle; Romoli, Benedetto; Curia, Giulia; Taylor, Seth R; Frady, E Paxon; Jensen, Anne B; Liu, Jerry C; Chaabane, Melanie M; Belal, Cherine; Nathanson, Jason L; Zoli, Michele; Leutgeb, Jill K; Biagini, Giuseppe; Yeo, Gene W; Berg, Darwin K

    2016-12-21

    A critical feature of neural networks is that they balance excitation and inhibition to prevent pathological dysfunction. How this is achieved is largely unknown, although deficits in the balance contribute to many neurological disorders. We show here that a microRNA (miR-101) is a key orchestrator of this essential feature, shaping the developing network to constrain excitation in the adult. Transient early blockade of miR-101 induces long-lasting hyper-excitability and persistent memory deficits. Using target site blockers in vivo, we identify multiple developmental programs regulated in parallel by miR-101 to achieve balanced networks. Repression of one target, NKCC1, initiates the switch in γ-aminobutyric acid (GABA) signaling, limits early spontaneous activity, and constrains dendritic growth. Kif1a and Ank2 are targeted to prevent excessive synapse formation. Simultaneous de-repression of these three targets completely phenocopies major dysfunctions produced by miR-101 blockade. Our results provide new mechanistic insight into brain development and suggest novel candidates for therapeutic intervention.

  9. Adult neural stem cells from the subventricular zone: a review of the neurosphere assay.

    PubMed

    Gil-Perotín, Sara; Duran-Moreno, María; Cebrián-Silla, Arantxa; Ramírez, Mónica; García-Belda, Paula; García-Verdugo, José Manuel

    2013-09-01

    The possibility of obtaining large numbers of cells with potential to become functional neurons implies a great advance in regenerative medicine. A source of cells for therapy is the subventricular zone (SVZ) where adult neural stem cells (NSCs) retain the ability to proliferate, self-renew, and differentiate into several mature cell types. The neurosphere assay, a method to isolate, maintain, and expand these cells has been extensively utilized by research groups to analyze the biological properties of aNSCs and to graft into injured brains from animal models. In this review we briefly describe the neurosphere assay and its limitations, the methods to optimize culture conditions, the identity and the morphology of aNSC-derived neurospheres (including new ultrastructural data). The controversy regarding the identity and "stemness" of cells within the neurosphere is revised. The fine morphology of neurospheres, described thoroughly, allows for phenotypical characterization of cells in the neurospheres and may reveal slight changes that indirectly inform about cell integrity, cell damage, or oncogenic transformation. Along this review we largely highlight the critical points that researchers have to keep in mind before extrapolating results or translating experimental transplantation of neurosphere-derived cells to the clinical setting.

  10. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

    SciTech Connect

    Capkovic, Katie L.; Stevenson, Severin; Johnson, Marc C.; Thelen, Jay J.; Cornelison, D.D.W.

    2008-04-15

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression.

  11. Neural and behavioral responses to attractiveness in adult and infant faces.

    PubMed

    Hahn, Amanda C; Perrett, David I

    2014-10-01

    Facial attractiveness provides a very powerful motivation for sexual and parental behavior. We therefore review the importance of faces to the study of neurobiological control of human reproductive motivations. For heterosexual individuals there is a common brain circuit involving the nucleus accumbens, the medial prefrontal, dorsal anterior cingulate and the orbitofrontal cortices that is activated more by attractive than unattractive faces, particularly for faces of the opposite sex. Behavioral studies indicate parallel effects of attractiveness on incentive salience or willingness to work to see faces. There is some evidence that the reward value of opposite sex attractiveness is more pronounced in men than women, perhaps reflecting the greater importance assigned to physical attractiveness by men when evaluating a potential mate. Sex differences and similarities in response to facial attractiveness are reviewed. Studies comparing heterosexual and homosexual observers indicate the orbitofrontal cortex and mediodorsal thalamus are more activated by faces of the desired sex than faces of the less-preferred sex, independent of observer gender or sexual orientation. Infant faces activate brain regions that partially overlap with those responsive to adult faces. Infant faces provide a powerful stimulus, which also elicits sex differences in behavior and brain responses that appear dependent on sex hormones. There are many facial dimensions affecting perceptions of attractiveness that remain unexplored in neuroimaging, and we conclude by suggesting that future studies combining parametric manipulation of face images, brain imaging, hormone assays and genetic polymorphisms in receptor sensitivity are needed to understand the neural and hormonal mechanisms underlying reproductive drives.

  12. Gene-environment interaction in programming hippocampal plasticity: focus on adult neurogenesis

    PubMed Central

    Koehl, Muriel

    2015-01-01

    Interactions between genes and environment are a critical feature of development and both contribute to shape individuality. They are at the core of vulnerability resiliency for mental illnesses. During the early postnatal period, several brain structures involved in cognitive and emotional processing, such as the hippocampus, still develop and it is likely that interferences with this neuronal development, which is genetically determined, might lead to long-lasting structural and functional consequences and increase the risk of developing psychopathology. One particular target is adult neurogenesis, which is involved in the regulation of cognitive and emotional processes. Insights into the dynamic interplay between genes and environmental factors in setting up individual rates of neurogenesis have come from laboratory studies exploring experience-dependent changes in adult neurogenesis as a function of individual’s genetic makeup. These studies have implications for our understanding of the mechanisms regulating adult neurogenesis, which could constitute a link between environmental challenges and psychopathology. PMID:26300723

  13. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone.

    PubMed

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis.

  14. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone

    PubMed Central

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  15. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    PubMed

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results.

  16. Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells.

    PubMed

    Oh, Hidemasa; Chi, Xuan; Bradfute, Steven B; Mishina, Yuji; Pocius, Jennifer; Michael, Lloyd H; Behringer, Richard R; Schwartz, Robert J; Entman, Mark L; Schneider, Michael D

    2004-05-01

    The evidence of cardiomyocyte proliferation in damaged heart implied cardiac regeneration might occur by resident or extra cardiac stem cells. However, the specification and origin of these cells remain unknown. Here, we report using fluorescence-activated cell sorting that cardiac progenitor cells resided in adult heart and colocalized with small capillary vessels, within the stem cell antigen (Sca-1) population expressing high telomerase activity. Notably, hematopoietic stem cells capable of efflux Hoechst 33342, termed side population cells, also were identified within the heart-derived cells. The cardiac progenitor cells (CD45(-)/CD34(-)) express neither cardiac muscle nor endothelial cell markers at an undifferentiated stage. The exposure of 5-azacytidine induced cardiac differentiation, which depends, in part, on Bmpr1a, a type IA receptor for bone morphogenetic protein (BMP). The capability of adult Sca1(+) cells to adopt a cardiac muscle in embryogenesis was substantiated by blastocyst injection, using progenitors from the adult hearts of transgenic mice that harbor a bacterial artificial chromosome expressing GFP via the Nkx-2.5 locus. Intravenously injected progenitors, shortly after ischemic/reperfusion, homed and functionally differentiated 3.5% of total left ventricle in the host myocardium. Differentiation included both fusion-independent and fusion-associated components, proved by the Cre/loxP donor/recipient system. Our studies suggest that endogenous cardiac progenitors reside in the adult heart, regenerate cardiomyocytes functionally, and integrate into the existing heart circuitry.

  17. On the plasticity of semantic generalizations: Children and adults modify their verb lexicalization biases in response to changing input

    PubMed Central

    Shafto, Carissa L.; Havasi, Catherine; Snedeker, Jesse

    2014-01-01

    Languages differ in how they package the components of an event into words to form sentences. For example, while some languages typically encode the manner of motion in the verb (e.g., running), others more often use verbs that encode the path (e.g., ascending). Prior research has demonstrated that children and adults have lexicalization biases; i.e. they assume that novel motion verbs will reflect the dominant pattern of their own language. These experiments explored the plasticity of these biases. In Experiments 1 and 2 we taught English-speaking adults motion verbs, varying the proportion of manner and path verbs in the training set; their interpretation of subsequent verbs closely reflected the probabilistic variation in the input. In Experiments 3 and 4, five-year-old children also systematically shifted their lexicalization biases to reflect the verbs that they were taught. We conclude that lexicalization biases are adaptive inferences about verb meaning that are updated on the basis of experience. PMID:24001149

  18. Determination of constitutive properties fromspherical indentation data using neural networks. Part i:the case of pure kinematic hardening in plasticity laws

    NASA Astrophysics Data System (ADS)

    Huber, N.; Tsakmakis, Ch.

    1999-06-01

    In this paper the power of neural networks in identifying material parameters fromdata obtained by spherical indentation is demonstrated for an academic problem (pure kinematichardening, given Youngs modulus) . To obtain a data basis for the training and validation of theneural network, numerous finite element simulations were carried out for various sets of materialparameters. The constitutive model describing finite deformation plasticity is formulated withnonlinear kinematic hardening of Armstrong-Frederick type. It was shown by Huber and Tsakmakis, 1998a that the depth-load response of a cyclic indentation process, consisting ofloading, unloading and reloading of the indenter displays a typical hysteresis loop for givenmaterial parameters. The inverse problem of leading the depth-load response back to the relatedparameters in the constitutive equations is solved using a neutral network.

  19. Mature neural responses to Infant-Directed Speech but not Adult-Directed Speech in Pre-Verbal Infants

    PubMed Central

    Peter, Varghese; Kalashnikova, Marina; Santos, Aimee; Burnham, Denis

    2016-01-01

    Infant directed speech (IDS), the speech register adults use when talking to infants, has been shown to have positive effects on attracting infants’ attention, language learning, and emotional communication. Here event related potentials (ERPs) are used to investigate the neural coding of IDS and ADS (adult directed speech) as well as their discrimination by both infants and adults. Two instances of the vowel /i/, one extracted from ADS and one from IDS, were presented to 9-month-old infants and adults in two oddball conditions: ADS standard/IDS deviant and IDS standard/ADS deviant. In Experiment 1 with adults, the obligatory ERPs that code acoustic information were different for ADS and IDS; and discrimination, indexed by mismatch negativity (MMN) responses, showed that IDS and ADS deviants were discriminated equally well; although, the P3a response was larger for IDS suggesting it captured adults’ attention more than did ADS. In infants the obligatory responses did not differ for IDS and ADS, but for discrimination, while IDS deviants generated both a slow-positive mismatch response (MMR) as well as an adult-like MMN, the ADS deviants generated only an MMR. The presence of a mature adult-like MMN suggests that the IDS stimulus is easier to discriminate for infants. PMID:27677352

  20. Regulating critical period plasticity: insight from the visual system to fear circuitry for therapeutic interventions.

    PubMed

    Nabel, Elisa M; Morishita, Hirofumi

    2013-01-01

    Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development - the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins - endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  1. Food restriction enhances visual cortex plasticity in adulthood.

    PubMed

    Spolidoro, Maria; Baroncelli, Laura; Putignano, Elena; Maya-Vetencourt, José Fernando; Viegi, Alessandro; Maffei, Lamberto

    2011-01-01

    Neural circuits display a heightened sensitivity to external stimuli during well-established windows in early postnatal life. After the end of these critical periods, brain plasticity dramatically wanes. The visual system is one of the paradigmatic models for studying experience-dependent plasticity. Here we show that food restriction can be used as a strategy to restore plasticity in the adult visual cortex of rats. A short period of food restriction in adulthood is able both to reinstate ocular dominance plasticity and promote recovery from amblyopia. These effects are accompanied by a reduction of intracortical inhibition without modulation of brain-derived neurotrophic factor expression or extracellular matrix structure. Our results suggest that food restriction could be investigated as a potential way of modulating plasticity.

  2. The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults.

    PubMed

    Habeck, C; Gazes, Y; Razlighi, Q; Steffener, J; Brickman, A; Barulli, D; Salthouse, T; Stern, Y

    2016-01-15

    Analyses of large test batteries administered to individuals ranging from young to old have consistently yielded a set of latent variables representing reference abilities (RAs) that capture the majority of the variance in age-related cognitive change: Episodic Memory, Fluid Reasoning, Perceptual Processing Speed, and Vocabulary. In a previous paper (Stern et al., 2014), we introduced the Reference Ability Neural Network Study, which administers 12 cognitive neuroimaging tasks (3 for each RA) to healthy adults age 20-80 in order to derive unique neural networks underlying these 4 RAs and investigate how these networks may be affected by aging. We used a multivariate approach, linear indicator regression, to derive a unique covariance pattern or Reference Ability Neural Network (RANN) for each of the 4 RAs. The RANNs were derived from the neural task data of 64 younger adults of age 30 and below. We then prospectively applied the RANNs to fMRI data from the remaining sample of 227 adults of age 31 and above in order to classify each subject-task map into one of the 4 possible reference domains. Overall classification accuracy across subjects in the sample age 31 and above was 0.80±0.18. Classification accuracy by RA domain was also good, but variable; memory: 0.72±0.32; reasoning: 0.75±0.35; speed: 0.79±0.31; vocabulary: 0.94±0.16. Classification accuracy was not associated with cross-sectional age, suggesting that these networks, and their specificity to the respective reference domain, might remain intact throughout the age range. Higher mean brain volume was correlated with increased overall classification accuracy; better overall performance on the tasks in the scanner was also associated with classification accuracy. For the RANN network scores, we observed for each RANN that a higher score was associated with a higher corresponding classification accuracy for that reference ability. Despite the absence of behavioral performance information in the

  3. Comparisons of the effects of a foam pad, mung bean bag, and plastic bead bag on postural stability disturbance in healthy young adults.

    PubMed

    Siriphorn, Akkradate; Chamonchant, Dannaovarat; Boonyong, Sujitra

    2016-01-01

    [Purpose] The aim of the present study was to compare the effects of unstable support surfaces, i.e. foam pad, mung bean bag, and plastic bead bag, on postural stability disturbance. [Subjects and Methods] Twenty-two healthy young adults (11 male and 11 female; aged 21.09 ± 1.44 years; BMI 20.40 ± 1.40 kg/m(2)) participated in the study. The Balance Master™ was used to evaluate the limit of stability and the unilateral stance performance. Each participant was assessed while standing on the following surfaces: 1) a firm surface, 2) a foam pad, 3) a mung bean bag, and 4) a plastic bead bag. The order of surfaces was randomly assigned. [Results] The mung bean bag and plastic bead bag showed greater disturbances in limit of stability and unilateral stance than the foam pad. There was no significant difference in postural stability disturbance between the mung bean bag and plastic bead bag. [Conclusion] These results suggested that both the mung bean bag and plastic bead bag could be used as a low-cost tool for balance assessment instead of a foam pad in healthy young adults.

  4. Comparisons of the effects of a foam pad, mung bean bag, and plastic bead bag on postural stability disturbance in healthy young adults

    PubMed Central

    Siriphorn, Akkradate; Chamonchant, Dannaovarat; Boonyong, Sujitra

    2016-01-01

    [Purpose] The aim of the present study was to compare the effects of unstable support surfaces, i.e. foam pad, mung bean bag, and plastic bead bag, on postural stability disturbance. [Subjects and Methods] Twenty-two healthy young adults (11 male and 11 female; aged 21.09 ± 1.44 years; BMI 20.40 ± 1.40 kg/m2) participated in the study. The Balance Master™ was used to evaluate the limit of stability and the unilateral stance performance. Each participant was assessed while standing on the following surfaces: 1) a firm surface, 2) a foam pad, 3) a mung bean bag, and 4) a plastic bead bag. The order of surfaces was randomly assigned. [Results] The mung bean bag and plastic bead bag showed greater disturbances in limit of stability and unilateral stance than the foam pad. There was no significant difference in postural stability disturbance between the mung bean bag and plastic bead bag. [Conclusion] These results suggested that both the mung bean bag and plastic bead bag could be used as a low-cost tool for balance assessment instead of a foam pad in healthy young adults. PMID:27065085

  5. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu

    PubMed Central

    Mansouri, Shiva; Lietzau, Grazyna; Lundberg, Mathias; Nathanson, David; Nyström, Thomas; Patrone, Cesare

    2016-01-01

    Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia. PMID:27305000

  6. Neural Cell Adhesion Molecule-Associated Polysialic Acid Regulates Synaptic Plasticity and Learning by Restraining the Signaling through GluN2B-Containing NMDA Receptors

    PubMed Central

    Kochlamazashvili, Gaga; Senkov, Oleg; Grebenyuk, Sergei; Robinson, Catrina; Xiao, Mei-Fang; Stummeyer, Katharina; Gerardy-Schahn, Rita; Engel, Andreas K.; Feig, Larry; Semyanov, Alexey; Suppiramaniam, Vishnu; Schachner, Melitta; Dityatev, Alexander

    2017-01-01

    The neural cell adhesion molecule (NCAM) is the predominant carrier of α2,8 polysialic acid (PSA) in the mammalian brain. Abnormalities in PSA and NCAM expression are associated with schizophrenia in humans and cause deficits in hippocampal synaptic plasticity and contextual fear conditioning in mice. Here, we show that PSA inhibits opening of recombinant NMDA receptors composed of GluN1/2B (NR1/NR2B) or GluN1/2A/2B (NR1/NR2A/NR2B) but not of GluN1/2A (NR1/NR2A) subunits. Deficits in NCAM/PSA increase GluN2B-mediated transmission and Ca2+ transients in the CA1 region of the hippocampus. In line with elevation of GluN2B-mediated transmission, defects in long-term potentiation in the CA1 region and contextual fear memory in NCAM/PSA-deficient mice are abrogated by application of a GluN2B-selective antagonist. Furthermore, treatment with the glutamate scavenger glutamic-pyruvic transaminase, ablation of Ras-GRF1 (a mediator of GluN2B signaling to p38 MAPK), or direct inhibition of hyperactive p38 MAPK can restore impaired synaptic plasticity in brain slices lacking PSA/NCAM. Thus, PSA carried by NCAM regulates plasticity and learning by inhibition of the GluN2B-Ras-GRF1-p38 MAPK signaling pathway. These findings implicate carbohydrates carried by adhesion molecules in modulating NMDA receptor signaling in the brain and demonstrate reversibility of cognitive deficits associated with ablation of a schizophrenia-related adhesion molecule. PMID:20237287

  7. EphrinB-EphB receptor signaling contributes to neuropathic pain by regulating neural excitability and spinal synaptic plasticity in rats.

    PubMed

    Song, Xue-Jun; Zheng, Ji-Hong; Cao, Jun-Li; Liu, Wen-Tao; Song, Xue-Song; Huang, Zhi-Jiang

    2008-09-30

    Bidirectional signaling between ephrins and Eph receptor tyrosine kinases was first found to play important roles during development, but recently has been implicated in synaptic plasticity and pain processing in the matured nervous system. We show that ephrinB-EphB receptor signaling plays a critical role is induction and maintenance of neuropathic pain by regulating neural excitability and synaptic plasticity in the dorsal root ganglion (DRG) and the spinal dorsal horn (DH). Intrathecal application of blocking reagents for EphB-receptors, EphB1-Fc and EphB2-Fc chimeras inhibits the induction and maintenance of nerve injury-induced thermal hyperalgesia and mechanical allodynia. These blockers also prevent and suppress the nerve injury-induced hyperexcitability of nociceptive small DRG neurons, sensitization of DH neurons and long-term potentiation (LTP) of synapses between C fibers and DH neurons. In naïve, uninjured animals intrathecal administration of EphB-receptor activators ephrinB1-Fc and ephrinB2-Fc, respectively, induces thermal hypersensitivity and lowers the threshold for LTP, while EphB1-Fc prevents induction of the LTP. Western Blot analysis shows that nerve injury triggers an upregulation of the ephrinB1 and EphB1 receptor proteins in DRG and the spinal cord. These results indicate that, by regulating excitability of nociceptive-related neurons in DRG and DH and the synaptic plasticity at the spinal level, ephrinB-EphB receptor signaling contributes to neuropathic pain. This novel role for ephrinB-EphB receptor signaling suggests that these molecules may be useful therapeutic targets for treating pain after nerve injury.

  8. Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats

    PubMed Central

    Choi, Ga-Young; Kim, Hyun-Bum; Hwang, Eun-Sang; Lee, Seok; Kim, Min-Ji; Choi, Ji-Young; Lee, Sung-Ok

    2017-01-01

    Curcumin is a major diarylheptanoid component of Curcuma longa with traditional usage for anxiety and depression. It has been known for the anti-inflammatory, antistress, and neurotropic effects. Here we examined curcumin effect in neural plasticity and cell viability. 60-channel multielectrode array was applied on organotypic hippocampal slice cultures (OHSCs) to monitor the effect of 10 μM curcumin in long-term depression (LTD) through low-frequency stimulation (LFS) to the Schaffer collaterals and commissural pathways. Cell viability was assayed by propidium iodide uptake test in OHSCs. In addition, the influence of oral curcumin administration on rat behavior was assessed with the forced swim test (FST). Finally, protein expression levels of brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2) were measured by Western blot in chronically stressed rats. Our results demonstrated that 10 μM curcumin attenuated LTD and reduced cell death. It also recovered the behavior immobility of FST, rescued the attenuated BDNF expression, and inhibited the enhancement of COX-2 expression in stressed animals. These findings indicate that curcumin can enhance postsynaptic electrical reactivity and cell viability in intact neural circuits with antidepressant-like effects, possibly through the upregulation of BDNF and reduction of inflammatory factors in the brain. PMID:28167853

  9. Plasticity of the histamine H3 receptors after acute vestibular lesion in the adult cat

    PubMed Central

    Tighilet, Brahim; Mourre, Christiane; Lacour, Michel

    2014-01-01

    After unilateral vestibular neurectomy (UVN) many molecular and neurochemical mechanisms underlie the neurophysiological reorganizations occurring in the vestibular nuclei (VN) complex, as well as the behavioral recovery process. As a key regulator, the histaminergic system appears to be a likely candidate because drugs interfering with histamine (HA) neurotransmission facilitate behavioral recovery after vestibular lesion. This study aimed at analyzing the post-lesion changes of the histaminergic system by quantifying binding to histamine H3 receptors (H3R; mediating namely histamine autoinhibition) using a histamine H3 receptor agonist ([3H]N-α-methylhistamine). Experiments were done in brain sections of control cats (N = 6) and cats submitted to UVN and killed 1 (N = 6) or 3 (N = 6) weeks after the lesion. UVN induced a bilateral decrease in binding density of the agonist [3H]N-α-methylhistamine to H3R in the tuberomammillary nuclei (TMN) at 1 week post-lesion, with a predominant down-regulation in the ipsilateral TMN. The bilateral decrease remained at the 3 weeks survival time and became symmetric. Concerning brainstem structures, binding density in the VN, the prepositus hypoglossi, the subdivisions of the inferior olive decreased unilaterally on the ipsilateral side at 1 week and bilaterally 3 weeks after UVN. Similar changes were observed in the subdivisions of the solitary nucleus only 1 week after the lesion. These findings indicate vestibular lesion induces plasticity of the histamine H3R, which could contribute to vestibular function recovery. PMID:24427120

  10. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone

    PubMed Central

    Shende, Vishvesh H.; McArthur, Simon; Gillies, Glenda E.; Opacka-Juffry, Jolanta

    2015-01-01

    The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally. PMID:26345609

  11. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone.

    PubMed

    Shende, Vishvesh H; McArthur, Simon; Gillies, Glenda E; Opacka-Juffry, Jolanta

    2015-01-01

    The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  12. A Behavioral Treatment for Traumatic Brain Injury-Associated Visual Dysfunction Based on Adult Cortical Plasticity

    DTIC Science & Technology

    2013-10-01

    balance between neuronal excitation or inhibition (He, Hodos & Quinlan, 2006,  Maya  Vetencourt, Sale, Viegi, Baroncelli, De Pasquale, O’Leary, Castren...adult visual cortex. J Neurosci, 26 (11), 2951‐2955.  Maya  Vetencourt, J.F., Sale, A., Viegi, A., Baroncelli, L., De Pasquale, R., O’Leary, O.F

  13. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation

    PubMed Central

    Barazzuol, Lara; Jeggo, Penny A.

    2016-01-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5–14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4Y288C), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4Y288C embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4Y288C mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  14. Plasticity of Adult Sensorimotor System in Severe Brain Infarcts: Challenges and Opportunities

    PubMed Central

    Sterr, Annette; Conforto, Adriana Bastos

    2012-01-01

    Functional reorganization forms the critical mechanism for the recovery of function after brain damage. These processes are driven by inherent changes within the central nervous system (CNS) triggered by the insult and further depend on the neural input the recovering system is processing. Therefore these processes interact with not only the interventions a patient receives, but also the activities and behaviors a patient engages in. In recent years, a wide range of research programs has addressed the association between functional reorganization and the spontaneous and treatment-induced recovery. The bulk of this work has focused on upper-limb and hand function, and today there are new treatments available that capitalize on the neuroplasticity of the brain. However, this is only true for patients with mild to moderated impairments; for those with very limited hand function, the basic understanding is much poorer and directly translates into limited treatment opportunities for these patients. The present paper aims to highlight the knowledge gap on severe stroke with a brief summary of the literature followed by a discussion of the challenges involved in the study and treatment of severe stroke and poor long-term outcome. PMID:22548196

  15. Early olfactory experience modifies neural activity in the antennal lobe of a social insect at the adult stage.

    PubMed

    Arenas, A; Giurfa, M; Farina, W M; Sandoz, J C

    2009-10-01

    In the antennal lobe (AL), the first olfactory centre of the insect brain, odorants are represented as spatiotemporal patterns of glomerular activity. Whether and how such patterns are modified in the long term after precocious olfactory experiences (i.e. in the first days of adulthood) remains unknown. To address this question, we used in vivo optical imaging of calcium activity in the antennal lobe of 17-day-old honeybees which either experienced an odorant associated with sucrose solution 5-8 days after emergence or were left untreated. In both cases, we imaged neural responses to the learned odor and to three novel odors varying in functional group and carbon-chain length. Two different odor concentrations were used. We also measured behavioral responses of 17-day-old honeybees, treated and untreated, to these stimuli. We show that precocious olfactory experience increased general odor-induced activity and the number of activated glomeruli in the adult AL, but also affected qualitative odor representations, which appeared shifted in the neural space of treated animals relative to control animals. Such effects were not limited to the experienced odor, but were generalized to other perceptually similar odors. A similar trend was found in behavioral experiments, in which increased responses to the learned odor extended to perceptually similar odors in treated bees. Our results show that early olfactory experiences have long-lasting effects, reflected in behavioral responses to odorants and concomitant neural activity in the adult olfactory system.

  16. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

    PubMed

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

    2014-08-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.

  17. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium

    PubMed Central

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J.; Klein, Ophir D.; Barlow, Linda A.

    2014-01-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. PMID:24993944

  18. Plasticity in the adult language system: a longitudinal electrophysiological study on second language learning.

    PubMed

    Stein, M; Dierks, T; Brandeis, D; Wirth, M; Strik, W; Koenig, T

    2006-11-01

    Event-related potentials (ERPs) were used to trace changes in brain activity related to progress in second language learning. Twelve English-speaking exchange students learning German in Switzerland were recruited. ERPs to visually presented single words from the subjects' native language (English), second language (German) and an unknown language (Romansh) were measured before (day 1) and after (day 2) 5 months of intense German language learning. When comparing ERPs to German words from day 1 and day 2, we found topographic differences between 396 and 540 ms. These differences could be interpreted as a latency shift indicating faster processing of German words on day 2. Source analysis indicated that the topographic differences were accounted for by shorter activation of left inferior frontal gyrus (IFG) on day 2. In ERPs to English words, we found Global Field Power differences between 472 and 644 ms. This may due to memory traces related to English words being less easily activated on day 2. Alternatively, it might reflect the fact that--with German words becoming familiar on day 2--English words loose their oddball character and thus produce a weaker P300-like effect on day 2. In ERPs to Romansh words, no differences were observed. Our results reflect plasticity in the neuronal networks underlying second language acquisition. They indicate that with a higher level of second language proficiency, second language word processing is faster and requires shorter frontal activation. Thus, our results suggest that the reduced IFG activation found in previous fMRI studies might not reflect a generally lower activation but rather a shorter duration of activity.

  19. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells.

    PubMed

    Pfenninger, Cosima V; Roschupkina, Teona; Hertwig, Falk; Kottwitz, Denise; Englund, Elisabet; Bengzon, Johan; Jacobsen, Sten Eirik; Nuber, Ulrike A

    2007-06-15

    Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.

  20. An Event Related Field Study of Rapid Grammatical Plasticity in Adult Second-Language Learners.

    PubMed

    Bastarrika, Ainhoa; Davidson, Douglas J

    2017-01-01

    The present study used magnetoencephalography (MEG) to investigate how Spanish adult learners of Basque respond to morphosyntactic violations after a short period of training on a small fragment of Basque grammar. Participants (n = 17) were exposed to violation and control phrases in three phases (pretest, training, generalization-test). In each phase participants listened to short Basque phrases and they judged whether they were correct or incorrect. During the pre-test and generalization-test, participants did not receive any feedback. During the training blocks feedback was provided after each response. We also ran two Spanish control blocks before and after training. We analyzed the event-related magnetic- field (ERF) recorded in response to a critical word during all three phases. In the pretest, classification was below chance and we found no electrophysiological differences between violation and control stimuli. Then participants were explicitly taught a Basque grammar rule. From the first training block participants were able to correctly classify control and violation stimuli and an evoked violation response was present. Although the timing of the electrophysiological responses matched participants' L1 effect, the effect size was smaller for L2 and the topographical distribution differed from the L1. While the L1 effect was bilaterally distributed on the auditory sensors, the L2 effect was present at right frontal sensors. During training blocks two and three, the violation-control effect size increased and the topography evolved to a more L1-like pattern. Moreover, this pattern was maintained in the generalization test. We conclude that rapid changes in neuronal responses can be observed in adult learners of a simple morphosyntactic rule, and that native-like responses can be achieved at least in small fragments of second language.

  1. An Event Related Field Study of Rapid Grammatical Plasticity in Adult Second-Language Learners

    PubMed Central

    Bastarrika, Ainhoa; Davidson, Douglas J.

    2017-01-01

    The present study used magnetoencephalography (MEG) to investigate how Spanish adult learners of Basque respond to morphosyntactic violations after a short period of training on a small fragment of Basque grammar. Participants (n = 17) were exposed to violation and control phrases in three phases (pretest, training, generalization-test). In each phase participants listened to short Basque phrases and they judged whether they were correct or incorrect. During the pre-test and generalization-test, participants did not receive any feedback. During the training blocks feedback was provided after each response. We also ran two Spanish control blocks before and after training. We analyzed the event-related magnetic- field (ERF) recorded in response to a critical word during all three phases. In the pretest, classification was below chance and we found no electrophysiological differences between violation and control stimuli. Then participants were explicitly taught a Basque grammar rule. From the first training block participants were able to correctly classify control and violation stimuli and an evoked violation response was present. Although the timing of the electrophysiological responses matched participants' L1 effect, the effect size was smaller for L2 and the topographical distribution differed from the L1. While the L1 effect was bilaterally distributed on the auditory sensors, the L2 effect was present at right frontal sensors. During training blocks two and three, the violation-control effect size increased and the topography evolved to a more L1-like pattern. Moreover, this pattern was maintained in the generalization test. We conclude that rapid changes in neuronal responses can be observed in adult learners of a simple morphosyntactic rule, and that native-like responses can be achieved at least in small fragments of second language. PMID:28174530

  2. Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity.

    PubMed

    Jorquera, Gonzalo; Altamirano, Francisco; Contreras-Ferrat, Ariel; Almarza, Gonzalo; Buvinic, Sonja; Jacquemond, Vincent; Jaimovich, Enrique; Casas, Mariana

    2013-03-01

    An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers. We have previously shown that voltage-gated L-type calcium channel (Cav1.1) acts as a voltage sensor for activation of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P₃]-dependent Ca(2+) signals that regulates gene expression. ATP released by muscle cells after electrical stimulation through pannexin-1 channels plays a key role in this process. We show now that stimulation frequency determines both ATP release and Ins(1,4,5)P₃ production in adult skeletal muscle and that Cav1.1 and pannexin-1 colocalize in the transverse tubules. Both ATP release and increased Ins(1,4,5)P₃ was seen in flexor digitorum brevis fibers stimulated with 270 pulses at 20 Hz, but not at 90 Hz. 20 Hz stimulation induced transcriptional changes related to fast-to-slow muscle fiber phenotype transition that required ATP release. Addition of 30 µM ATP to fibers induced the same transcriptional changes observed after 20 Hz stimulation. Myotubes lacking the Cav1.1-α1 subunit released almost no ATP after electrical stimulation, showing that Cav1.1 has a central role in this process. In adult muscle fibers, ATP release and the transcriptional changes produced by 20 Hz stimulation were blocked by both the Cav1.1 antagonist nifedipine (25 µM) and by the Cav1.1 agonist (-)S-BayK 8644 (10 µM). We propose a new role for Cav1.1, independent of its calcium channel activity, in the activation of signaling pathways allowing muscle fibers to decipher the frequency of electrical stimulation and to activate specific transcriptional programs that define their phenotype.

  3. Neural Stem Cells in the Adult Subventricular Zone Oxidize Fatty Acids to Produce Energy and Support Neurogenic Activity.

    PubMed

    Stoll, Elizabeth A; Makin, Rebecca; Sweet, Ian R; Trevelyan, Andrew J; Miwa, Satomi; Horner, Philip J; Turnbull, Douglass M

    2015-07-01

    Neural activity is tightly coupled to energy consumption, particularly sugars such as glucose. However, we find that, unlike mature neurons and astrocytes, neural stem/progenitor cells (NSPCs) do not require glucose to sustain aerobic respiration. NSPCs within the adult subventricular zone (SVZ) express enzymes required for fatty acid oxidation and show sustained increases in oxygen consumption upon treatment with a polyunsaturated fatty acid. NSPCs also demonstrate sustained decreases in oxygen consumption upon treatment with etomoxir, an inhibitor of fatty acid oxidation. In addition, etomoxir decreases the proliferation of SVZ NSPCs without affecting cellular survival. Finally, higher levels of neurogenesis can be achieved in aged mice by ectopically expressing proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), a factor that increases cellular aerobic capacity by promoting mitochondrial biogenesis and metabolic gene transcription. Regulation of metabolic fuel availability could prove a powerful tool in promoting or limiting cellular proliferation in the central nervous system. Stem Cells 2015;33:2306-2319.

  4. Cyclin E marks quiescent neural stem cells and caspase-3-positive newborn cells during adult hippocampal neurogenesis in mice.

    PubMed

    Ikeda, Yayoi; Ikeda, Masa-Aki

    2015-10-21

    Cyclin E is a key regulator of progression through the G1-phase of the cell cycle. Recently, a cell cycle-independent role for cyclin E in the adult mouse central nervous system has been suggested. In the present study, we examined expression of cyclin E in the mouse hippocampal dentate gyrus (DG), a region of neurogenesis in adulthood, using immunofluorescence. In the adult DG, cyclin E-immunoreactive (cyclin E+) cells was limited to postmitotic cells. In the subgranular zone, cyclin E was detected in the vertical process of radial glia-like cells, which were marked by the neural stem cell markers nestin and GFAP. Cyclin E was also detected in the nucleus of cells, which were labeled with stage-specific neuronal cell markers, including Pax6, Sox2, NeuroD, doublecortin, and NeuN. The densities of cyclin E+ cells in the DG reduced and increased with age and running, respectively. Furthermore, the majority of cyclin E+ cells co-expressed active caspase-3, a marker of apoptosis. Together, the results indicate that cyclin E is expressed in the process of quiescent neural stem cells and in the nucleus of active caspase-3+ cells during neuronal cell differentiation, suggesting that cyclin E has a Cdk-independent function, which might be important for the mechanisms regulating adult hippocampal neurogenesis.

  5. The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.

    PubMed

    Ninkovic, Jovica; Steiner-Mezzadri, Andrea; Jawerka, Melanie; Akinci, Umut; Masserdotti, Giacomo; Petricca, Stefania; Fischer, Judith; von Holst, Alexander; Beckers, Johanes; Lie, Chichung D; Petrik, David; Miller, Erik; Tang, Jiong; Wu, Jiang; Lefebvre, Veronique; Demmers, Jeroen; Eisch, Amelia; Metzger, Daniel; Crabtree, Gerald; Irmler, Martin; Poot, Raymond; Götz, Magdalena

    2013-10-03

    Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.

  6. Gene Expression Profile of Adult Human Olfactory Bulb and Embryonic Neural Stem Cell Suggests Distinct Signaling Pathways and Epigenetic Control

    PubMed Central

    Marei, Hany E. S.; Ahmed, Abd-Elmaksoud; Michetti, Fabrizio; Pescatori, Mario; Pallini, Roberto; Casalbore, Patricia; Cenciarelli, Carlo; Elhadidy, Mohamed

    2012-01-01

    Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults. PMID:22485144

  7. The pregnane xenobiotic receptor, a prominent liver factor, has actions in the midbrain for neurosteroid synthesis and behavioral/neural plasticity of female rats

    PubMed Central

    Frye, Cheryl A.; Koonce, Carolyn J.; Walf, Alicia A.

    2014-01-01

    A novel factor of interest for growth/plasticity in the brain is pregnane xenobiotic receptor (PXR). PXR is a liver factor known for its role in xenobiotic clearance and cholesterol metabolism. It is expressed in the brain, suggesting a potential role for plasticity, particularly involving cholesterol-based steroids and neurosteroids. Mating induces synthesis of neurosteroids in the midbrain Ventral Tegmental Area (VTA) of female rodents, as well as other “plastic” regions of the brain, including the hippocampus, that may be involved in the consolidation of the mating experience. Reducing PXR in the VTA attenuates mating-induced biosynthesis of the neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP). The 18 kDA translocator protein (TSPO) is one rate-limiting factor for 3α,5α-THP neurosteroidogenesis. The hypothesis tested was that PXR is an upstream factor of TSPO for neurosteroidogenesis of 3α,5α-THP in the VTA for lordosis, independent of peripheral glands. First, proestrous rats were administered a TSPO blocker (PK11195) and/or 3α,5α-THP following infusions of PXR antisense oligonucleotides (AS-ODNs) or vehicle to the VTA. Inhibiting TSPO with PK11195 reduced 3α,5α-THP levels in the midbrain and lordosis, an effect that could be reversed with 3α,5α-THP administration, but not AS-ODN+3α,5α-THP. Second, proestrous, ovariectomized (OVX), or ovariectomized/adrenalectomized (OVX/ADX) rats were infused with a TSPO enhancer (FGIN 1-27) subsequent to AS-ODNs or vehicle to the VTA. PXR AS-ODNs blocked actions of FGIN 1–27 for lordosis and 3α,5α-THP levels among proestrous > OVX > OVX/ADX rats. Thus, PXR may be upstream of TSPO, involved in neurosteroidogenesis of 3α,5α-THP in the brain for plasticity. This novel finding of a liver factor involved in behavioral/neural plasticity substantiates future studies investigating factors known for their prominent actions in the peripheral organs, such as the liver, for modulating brain function and its

  8. Impaired neural transmission and synaptic plasticity in superior cervical ganglia from β-amyloid rat model of Alzheimer's disease.

    PubMed

    Alzoubi, K H; Alhaider, I A; Tran, T T; Mosely, A; Alkadhi, K K

    2011-06-01

    Basal synaptic transmission and activity-dependent synaptic plasticity were evaluated in superior cervical sympathetic ganglia (SCG) of amyloid-β rat model of Alzheimer's disease (Aβ rat) using electrophysiological and molecular techniques. Rats were administered Aβ peptides (a mixture of 1:1 Aβ1-40 and Aβ1-42) by chronic intracerebroventricular infusion via 14-day mini-osmotic pumps (300 pmol/day). Control rats received Aβ40-1 (inactive reverse peptide: 300 pmol/day). Ganglionic compound action potentials were recorded before (basal) and after repetitive stimulation. In isolated SCG, ganglionic long-term potentiation (gLTP) was generated by a brief train of stimuli (20Hz for 20s) and ganglionic long-term depression (gLTD) was produced with trains of paired pulses. The input/output (I/O) curves of ganglia from Aβ rats showed a marked downward shift along all stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission. In addition, repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals, but, the same protocols failed to induce gLTP or gLTD in ganglia from Aβ rats indicating impairment of activity-dependent synaptic plasticity in these animals. Western blotting of SCG homogenate from Aβ rats revealed reduction in the ratio of phosphorylated-/total-CaMKII and in calcineurin protein levels. Although other mechanisms could be involved, these changes in signaling molecules could represent an important molecular mechanism linked to the failure to express synaptic plasticity in Aβ rat ganglia. Results of the current study could explain some of the peripheral nervous system manifestations of Alzheimer's disease.

  9. Environmental exposure to the plasticizer 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) in US adults (2000—2012)

    PubMed Central

    Silva, Manori J.; Jia, Tao; Samandar, Ella; Preau, James L.; Calafat, Antonia M.

    2015-01-01

    1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a complex mixture of nine carbon branched-chain isomers. It has been used in Europe since 2002 as a plasticizer to replace phthalates such as di(2-ethylhexyl)phthalate (DEHP) and diisononyl phthalate (DINP). Urinary concentrations of the oxidative metabolites of DINCH, namely cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (MCOCH); cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester (MONCH); and cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (MHNCH), can potentially be used as DINCH exposure biomarkers. The concentrations of MCOCH, MONCH and MHNCH were measured by online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry in urine collected in 2000 (n=114), 2001 (n=57), 2007 (n=23), 2009 (n=118), 2011 (n=94) and 2012 (n=121) from convenience groups of anonymous U.S. adult volunteers with no known DINCH exposure. None of the DINCH metabolites were detected in samples collected in 2000 and 2001. Only one sample collected in 2007 had measureable concentrations of DINCH metabolites. The detection rate for all three metabolites increased from 2007 to 2012. The presence of oxidative metabolites of DINCH in urine suggests that these oxidative metabolites can be used as DINCH biomarkers for exposure assessment even at environmental exposure levels. PMID:23777640

  10. Doublecortin-positive cells in the adult primate cerebral cortex and possible role in brain plasticity and development.

    PubMed

    Bloch, Jocelyne; Kaeser, Mélanie; Sadeghi, Yalda; Rouiller, Eric M; Redmond, D Eugene; Brunet, Jean-François

    2011-03-01

    We have demonstrated that cortical cell autografts might be a useful therapy in two monkey models of neurological disease: motor cortex lesion and Parkinson's disease. However, the origin of the useful transplanted cells obtained from cortical biopsies is not clear. In this report we describe the expression of doublecortin (DCX) in these cells based on reverse-transcription polymerase chain reaction (RT-PCR) and immunodetection in the adult primate cortex and cell cultures. The results showed that DCX-positive cells were present in the whole primate cerebral cortex and also expressed glial and/or neuronal markers such as glial fibrillary protein (GFAP) or neuronal nuclei (NeuN). We also demonstrated that only DCX/GFAP positive cells were able to proliferate and originate progenitor cells in vitro. We hypothesize that these DCX-positive cells in vivo have a role in cortical plasticity and brain reaction to injury. Moreover, in vitro these DCX-positive cells have the potential to reacquire progenitor characteristics that confirm their potential for brain repair.

  11. Hippocampal synaptic plasticity: effects of neonatal stress in freely moving adult male rats.

    PubMed

    Petrosino, M; Bronzino, J D; Pizzuti, G P

    1999-01-01

    The present study examines the effects of neonatal isolation on hippocampal LTP in adult male rats. Changes in dentate granule cell population measures, i.e., EPSP slope and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway were used to assess the effects of neonatal isolation on LTP over a period of 96 h. Following tetanization significant group differences were obtained for input/output (I/O) response measures of EPSP slope and PSA, with isolated males showing consistently higher values than in the other two groups. Comparisons made at 1 h post-tetanization (establishment of LTP) indicated that isolated males showed significantly greater enhancement than any other group. At 96 h (maintenance of LTP), however, neonatally isolated males showed significantly greater enhancement than either non-isolated siblings or unhandled controls. Additionally, isolation resulted in prolonging the duration of enhancement obtained from males. Thus, males show different enhancement profiles with respect to both the magnitude and duration of LTP and neonatal isolation alters these profiles in profound manner.

  12. Plasticity of Astrocytic Coverage and Glutamate Transporter Expression in Adult Mouse Cortex

    PubMed Central

    Steiner, Pascal; Hirling, Harald; Welker, Egbert; Knott, Graham W

    2006-01-01

    Astrocytes play a major role in the removal of glutamate from the extracellular compartment. This clearance limits the glutamate receptor activation and affects the synaptic response. This function of the astrocyte is dependent on its positioning around the synapse, as well as on the level of expression of its high-affinity glutamate transporters, GLT1 and GLAST. Using Western blot analysis and serial section electron microscopy, we studied how a change in sensory activity affected these parameters in the adult cortex. Using mice, we found that 24 h of whisker stimulation elicited a 2-fold increase in the expression of GLT1 and GLAST in the corresponding cortical column of the barrel cortex. This returns to basal levels 4 d after the stimulation was stopped, whereas the expression of the neuronal glutamate transporter EAAC1 remained unaltered throughout. Ultrastructural analysis from the same region showed that sensory stimulation also causes a significant increase in the astrocytic envelopment of excitatory synapses on dendritic spines. We conclude that a period of modified neuronal activity and synaptic release of glutamate leads to an increased astrocytic coverage of the bouton–spine interface and an increase in glutamate transporter expression in astrocytic processes. PMID:17048987

  13. Neurobiological markers of exercise-related brain plasticity in older adults.

    PubMed

    Voss, Michelle W; Erickson, Kirk I; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; Phillips, Siobhan M; Wójcicki, Thomas R; Mailey, Emily L; Olson, Erin A; Gothe, Neha; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Cook, Marc D; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2013-02-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

  14. Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification.

    PubMed

    Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K

    2014-01-01

    Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs), differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  15. P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone.

    PubMed

    Messemer, Nanette; Kunert, Christin; Grohmann, Marcus; Sobottka, Helga; Nieber, Karen; Zimmermann, Herbert; Franke, Heike; Nörenberg, Wolfgang; Straub, Isabelle; Schaefer, Michael; Riedel, Thomas; Illes, Peter; Rubini, Patrizia

    2013-10-01

    Neurogenesis requires the balance between the proliferation of newly formed progenitor cells and subsequent death of surplus cells. RT-PCR and immunocytochemistry demonstrated the presence of P2X7 receptor mRNA and immunoreactivity in cultured neural progenitor cells (NPCs) prepared from the adult mouse subventricular zone (SVZ). Whole-cell patch-clamp recordings showed a marked potentiation of the inward current responses both to ATP and the prototypic P2X7 receptor agonist dibenzoyl-ATP (Bz-ATP) at low Ca(2+) and zero Mg(2+) concentrations in the bath medium. The Bz-ATP-induced currents reversed their polarity near 0 mV; in NPCs prepared from P2X7(-/-) mice, Bz-ATP failed to elicit membrane currents. The general P2X/P2Y receptor antagonist PPADS and the P2X7 selective antagonists Brilliant Blue G and A-438079 strongly depressed the effect of Bz-ATP. Long-lasting application of Bz-ATP induced an initial current, which slowly increased to a steady-state response. In combination with the determination of YO-PRO uptake, these experiments suggest the dilation of a receptor-channel and/or the recruitment of a dye-uptake pathway. Ca(2+)-imaging by means of Fura-2 revealed that in a Mg(2+)-deficient bath medium Bz-ATP causes [Ca(2+)](i) transients fully depending on the presence of external Ca(2+). The MTT test indicated a concentration-dependent decrease in cell viability by Bz-ATP treatment. Correspondingly, Bz-ATP led to an increase in active caspase 3 immunoreactivity, indicating a P2X7-controlled apoptosis. In acute SVZ brain slices of transgenic Tg(nestin/EGFP) mice, patch-clamp recordings identified P2X7 receptors at NPCs with pharmacological properties identical to those of their cultured counterparts. We suggest that the apoptotic/necrotic P2X7 receptors at NPCs may be of particular relevance during pathological conditions which lead to increased ATP release and thus could counterbalance the ensuing excessive cell proliferation.

  16. Can older adults resist the positivity effect in neural responding? The impact of verbal framing on event-related brain potentials elicited by emotional images.

    PubMed

    Rehmert, Andrea E; Kisley, Michael A

    2013-10-01

    Older adults have demonstrated an avoidance of negative information, presumably with a goal of greater emotional satisfaction. Understanding whether avoidance of negative information is a voluntary, motivated choice or an involuntary, automatic response will be important to differentiate, as decision making often involves emotional factors. With the use of an emotional framing event-related potential (ERP) paradigm, the present study investigated whether older adults could alter neural responses to negative stimuli through verbal reframing of evaluative response options. The late positive potential (LPP) response of 50 older adults and 50 younger adults was recorded while participants categorized emotional images in one of two framing conditions: positive ("more or less positive") or negative ("more or less negative"). It was hypothesized that older adults would be able to overcome a presumed tendency to down-regulate neural responding to negative stimuli in the negative framing condition, thus leading to larger LPP wave amplitudes to negative images. A similar effect was predicted for younger adults, but for positively valenced images, such that LPP responses would be increased in the positive framing condition compared with the negative framing condition. Overall, younger adults' LPP wave amplitudes were modulated by framing condition, including a reduction in the negativity bias in the positive frame. Older adults' neural responses were not significantly modulated, even though task-related behavior supported the notion that older adults were able to successfully adopt the negative framing condition.

  17. Functional plasticity of regenerated and intact taste receptors in adult rats unmasked by dietary sodium restriction.

    PubMed

    Hill, D L; Phillips, L M

    1994-05-01

    Unilateral chorda tympani nerve sectioning was combined with institution of a sodium-restricted diet in adult rats to determine the role that environment has on the functional properties of regenerating taste receptor cells. Rats receiving chorda tympani sectioning but no dietary manipulation (cut controls) and rats receiving only the dietary manipulation (diet controls) had normal responses to a concentration series of NaCl, sodium acetate (NaAc), and NH4Cl. However, responses from the regenerated nerve in NaCl-restricted rats (40-120 d postsectioning) to NaCl and NaAc were reduced by as much as 30% compared to controls, indicating that regenerating taste receptors are influenced by environmental (dietary) factors. Responses to NH4Cl were normal; therefore, the effect appears specific to sodium salts. Surprisingly, in the same rats, NaCl responses from the contralateral, intact chorda tympani were up to 40% greater than controls. Thus, in the same rat, there was over a twofold difference in sodium responses between the right and left chorda tympani nerves. A study of the time course of the functional alterations in the intact nerve revealed that responses to NaCl were extremely low immediately following sectioning (about 20% of the normal response), and then increased monotonically during the following 50 d until relative response magnitudes became supersensitive. This function occurred even when the cut chorda tympani was prevented from reinnervating lingual epithelia, demonstrating that events related to regeneration do not play a role in the functional properties of the contralateral side of the tongue.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Plasticity in adult cat visual cortex (area 17) following circumscribed monocular lesions of all retinal layers

    PubMed Central

    Calford, M B; Wang, C; Taglianetti, V; Waleszczyk, W J; Burke, W; Dreher, B

    2000-01-01

    In eight adult cats intense, sharply circumscribed, monocular laser lesions were used to remove all cellular layers of the retina. The extents of the retinal lesions were subsequently confirmed with counts of α-ganglion cells in retinal whole mounts; in some cases these revealed radial segmental degeneration of ganglion cells distal to the lesion.Two to 24 weeks later, area 17 (striate cortex; V1) was studied electrophysiologically in a standard anaesthetized, paralysed (artificially respired) preparation. Recording single- or multineurone activity revealed extensive topographical reorganization within the lesion projection zone (LPZ).Thus, with stimulation of the lesioned eye, about 75 % of single neurones in the LPZ had ‘ectopic’ visual discharge fields which were displaced to normal retina in the immediate vicinity of the lesion.The sizes of the ectopic discharge fields were not significantly different from the sizes of the normal discharge fields. Furthermore, binocular cells recorded from the LPZ, when stimulated via their ectopic receptive fields, exhibited orientation tuning and preferred stimulus velocities which were indistinguishable from those found when the cells were stimulated via the normal eye.However, the responses to stimuli presented via ectopic discharge fields were generally weaker (lower peak discharge rates) than those to presentations via normal discharge fields, and were characterized by a lower-than-normal upper velocity limit.Overall, the properties of the ectopic receptive fields indicate that cortical mechanisms rather than a retinal ‘periphery’ effect underlie the topographic reorganization of area 17 following monocular retinal lesions. PMID:10767137

  19. Reading in the dark: neural correlates and cross-modal plasticity for learning to read entire words without visual experience.

    PubMed

    Sigalov, Nadine; Maidenbaum, Shachar; Amedi, Amir

    2016-03-01

    Cognitive neuroscience has long attempted to determine the ways in which cortical selectivity develops, and the impact of nature vs. nurture on it. Congenital blindness (CB) offers a unique opportunity to test this question as the brains of blind individuals develop without visual experience. Here we approach this question through the reading network. Several areas in the visual cortex have been implicated as part of the reading network, and one of the main ones among them is the VWFA, which is selective to the form of letters and words. But what happens in the CB brain? On the one hand, it has been shown that cross-modal plasticity leads to the recruitment of occipital areas, including the VWFA, for linguistic tasks. On the other hand, we have recently demonstrated VWFA activity for letters in contrast to other visual categories when the information is provided via other senses such as touch or audition. Which of these tasks is more dominant? By which mechanism does the CB brain process reading? Using fMRI and visual-to-auditory sensory substitution which transfers the topographical features of the letters we compare reading with semantic and scrambled conditions in a group of CB. We found activation in early auditory and visual cortices during the early processing phase (letter), while the later phase (word) showed VWFA and bilateral dorsal-intraparietal activations for words. This further supports the notion that many visual regions in general, even early visual areas, also maintain a predilection for task processing even when the modality is variable and in spite of putative lifelong linguistic cross-modal plasticity. Furthermore, we find that the VWFA is recruited preferentially for letter and word form, while it was not recruited, and even exhibited deactivation, for an immediately subsequent semantic task suggesting that despite only short sensory substitution experience orthographic task processing can dominate semantic processing in the VWFA. On a wider

  20. Natural and Drug Rewards Act on Common Neural Plasticity Mechanisms with ΔFosB as a Key Mediator

    PubMed Central

    Pitchers, Kyle K.; Vialou, Vincent; Nestler, Eric J.; Laviolette, Steven R.; Lehman, Michael N.

    2013-01-01

    Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. Recent evidence suggests that natural rewards may cause similar changes in the NAc, suggesting that drugs may activate mechanisms of plasticity shared with natural rewards, and allowing for unique interplay between natural and drug rewards. In this study, we demonstrate that sexual experience in male rats when followed by short or prolonged periods of loss of sex reward causes enhanced amphetamine reward, indicated by sensitized conditioned place preference for low-dose (0.5 mg/kg) amphetamine. Moreover, the onset, but not the longer-term expression, of enhanced amphetamine reward was correlated with a transient increase in dendritic spines in the NAc. Next, a critical role for the transcription factor ΔFosB in sex experience-induced enhanced amphetamine reward and associated increases in dendritic spines on NAc neurons was established using viral vector gene transfer of the dominant-negative binding partner ΔJunD. Moreover, it was demonstrated that sexual experience-induced enhanced drug reward, ΔFosB, and spinogenesis are dependent on mating-induced dopamine D1 receptor activation in the NAc. Pharmacological blockade of D1 receptor, but not D2 receptor, in the NAc during sexual behavior attenuated ΔFosB induction and prevented increased spinogenesis and sensitized amphetamine reward. Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. PMID:23426671

  1. Brain self-protection: the role of endogenous neural progenitor cells in adult brain after cerebral cortical ischemia.

    PubMed

    Li, Bin; Piao, Chun-Shu; Liu, Xiao-Yun; Guo, Wen-Ping; Xue, Yue-Qiang; Duan, Wei-Ming; Gonzalez-Toledo, Maria E; Zhao, Li-Ru

    2010-04-23

    Convincing evidence has shown that brain ischemia causes the proliferation of neural stem cells/neural progenitor cells (NSCs/NPCs) in both the subventricular zone (SVZ) and the subgranular zone (SGZ) of adult brain. The role of brain ischemia-induced NSC/NPC proliferation, however, has remained unclear. Here we have determined whether brain ischemia-induced amplification of the NSCs/NPCs in adult brain is required for brain self-protection. The approach of intracerebroventricular (ICV) infusion of cytosine arabinoside (Ara-C), an inhibitor for cell proliferation, for the first 7days after brain ischemia was used to block ischemia-induced NSC/NPC proliferation. We observed that ICV infusion of Ara-C caused a complete blockade of NSC/NPC proliferation in the SVZ and a dramatic reduction of NSC/NPC proliferation in the SGZ. Additionally, as a result of the inhibition of ischemia-induced NSC/NPC pool amplification, the number of neurons in the hippocampal CA1 and CA3 was significantly reduced, the infarction size was significantly enlarged, and neurological deficits were significantly worsened after focal brain ischemia. We also found that an NSC/NPC-conditioned medium showed neuroprotective effects in vitro and that adult NSC/NPC-released brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are required for NSC/NPC-conditioned medium-induced neuroprotection. These data suggest that NSC/NPC-generated trophic factors are neuroprotective and that brain ischemia-triggered NSC/NPC proliferation is crucial for brain protection. This study provides insights into the contribution of endogenous NSCs/NPCs to brain self-protection in adult brain after ischemia injury.

  2. Microenvironmental determinants of adult neural stem cell proliferation and lineage commitment in the healthy and injured central nervous system.

    PubMed

    Moyse, Emmanuel; Segura, Stéphanie; Liard, Oliver; Mahaut, Stéphanie; Mechawar, Naguib

    2008-09-01

    The discovery of neural stem cells (NSC) which ensure continuous neurogenesis in the adult mammalian brain, has led to a conceptual revolution in basic neuroscience and to high hopes for clinical nervous tissue repair. However, several research issues remain to address before neural stem cells can be harnessed for regenerative therapies. The presence of NSC in a nervous structure is demonstrated in vitro by primary culture of dissociated adult nervous tissue in the presence of the specific mitogens EGF and bFGF. This leads to spherical masses of proliferating cells endowed with capacities for self-renewal and, after growth factor removal, differentiation into the three characteristic cell types of nervous tissue (neurons, astrocytes, oligodendrocytes). In vivo, neurogenesis per se, i.e. production of new neurons, occurs only in a small subset of NSC-endowed structures. The production of oligodendrocytes, i.e. myelinating glial cells, is similarly restricted. Such in vivo restrictions were formally demonstrated to arise from the tissular microenvironnement, which led to the emerging concept of "neurogenic niche". In this context, major challenges now consist in identifying the nature of tissue-specific extracellular signals that determine lineage commitment of NSC progeny, understanding why NSCs display weak in vivo reactivity to lesions compared to other stem cell types in adults, and identifying the factors behind the very high resistance to tumorigenesis displayed by NSCs. Altogether, the current data offer hope for the future use of adult NSCs in regenerative therapies, provided that tissue-specific signals are identified in view of counteracting the intrinsic repression of new cell genesis and/or stimulating endogenous NSC recruitment to lesion sites.

  3. Cortical and thalamic connectivity of the auditory anterior ectosylvian cortex of early-deaf cats: Implications for neural mechanisms of crossmodal plasticity

    PubMed Central

    Meredith, M. Alex; Clemo, H. Ruth; Corley, Sarah B.; Chabot, Nicole; Lomber, Stephen G.

    2016-01-01

    Early hearing loss leads to crossmodal plasticity in regions of the cerebrum that are dominated by acoustical processing in hearing subjects. Until recently, little has been known of the connectional basis of this phenomenon. One region whose crossmodal properties are well-established is the auditory field of the anterior ectosylvian sulcus (FAES) in the cat, where neurons are normally responsive to acoustic stimulation and its deactivation leads to the behavioral loss of accurate orienting toward auditory stimuli. However, in early-deaf cats, visual responsiveness predominates in the FAES and its deactivation blocks accurate orienting behavior toward visual stimuli. For such crossmodal reorganization to occur, it has been presumed that novel inputs or increased projections from non-auditory cortical areas must be generated, or that existing non-auditory connections were ‘unmasked.’ These possibilities were tested using tracer injections into the FAES of adult cats deafened early in life (and hearing controls), followed by light microscopy to localize retrogradely labeled neurons. Surprisingly, the distribution of cortical and thalamic afferents to the FAES was very similar among early-deaf and hearing animals. No new visual projection sources were identified and visual cortical connections to the FAES were comparable in projection proportions. These results support an alternate theory for the connectional basis for cross-modal plasticity that involves enhanced local branching of existing projection terminals that originate in non-auditory as well as auditory cortices. PMID:26724756

  4. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    PubMed

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  5. Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells

    PubMed Central

    Chung, Kyung Min; Jeong, Eun-Ji; Park, Hyunhee; An, Hyun-Kyu; Yu, Seong-Woon

    2016-01-01

    Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs) and inositol 1,4,5-triphosphate receptors (IP3Rs), the main Ca2+ release channels located in endoplasmic reticulum (ER) membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN) cells utilizing an insulin withdrawal model of autophagic cell death (ACD). Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs—especially RyR3—were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished ACD of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology. PMID:27199668

  6. As Working Memory Grows: A Developmental Account of Neural Bases of Working Memory Capacity in 5- to 8-Year Old Children and Adults.

    PubMed

    Kharitonova, Maria; Winter, Warren; Sheridan, Margaret A

    2015-09-01

    Working memory develops slowly: Even by age 8, children are able to maintain only half the number of items that adults can remember. Neural substrates that support performance on working memory tasks also have a slow developmental trajectory and typically activate to a lesser extent in children, relative to adults. Little is known about why younger participants elicit less neural activation. This may be due to maturational differences, differences in behavioral performance, or both. Here we investigate the neural correlates of working memory capacity in children (ages 5-8) and adults using a visual working memory task with parametrically increasing loads (from one to four items) using fMRI. This task allowed us to estimate working memory capacity limit for each group. We found that both age groups increased the activation of frontoparietal networks with increasing working memory loads, until working memory capacity was reached. Because children's working memory capacity limit was half of that for adults, the plateau occurred at lower loads for children. Had a parametric increase in load not been used, this would have given an impression of less activation overall and less load-dependent activation for children relative to adults. Our findings suggest that young children and adults recruit similar frontoparietal networks at working memory loads that do not exceed capacity and highlight the need to consider behavioral performance differences when interpreting developmental differences in neural activation.

  7. Chemokines influence the migration and fate of neural precursor cells from the young adult and middle-aged rat subventricular zone.

    PubMed

    Gordon, R J; Mehrabi, N F; Maucksch, C; Connor, B

    2012-01-01

    We have previously demonstrated a role for the chemokines MCP-1, MIP-1α and GRO-α in directing subventricular zone (SVZ)-derived neural precursor cell migration towards the site of cell death in the adult rodent brain. However the influence of chemokines such as MCP-1, MIP-1α and GRO-α on the differentiation of adult neural precursor cells has not previously been investigated. Further, as the majority of neurological disorders and injuries occur during ageing, it is important to investigate the effect of chemokines on adult neural precursor cell cultures obtained from the ageing brain. This study therefore examined the effect of MCP-1, MIP-1α and GRO-α on SVZ-derived neural precursor cell differentiation in vitro, and assessed whether precursor cells from the middle-aged rat brain (13 months old) follow the same migratory and differential profile as neural precursor cells obtained from the young adult rat brain (2 months old). We observed that each of the chemokines examined generated differing effects in regards to neuronal or glial differentiation. Further, both MIP-1α and GRO-α increased total cell number, suggesting an effect on precursor cell proliferation and/or survival. In agreement with cultures obtained from young adult brains, SVZ-derived neural precursor cells cultured from the middle-aged brain exhibited chemotactic migration in response to a concentration gradient. These results indicate that the chemokines MCP-1, MIP-1α and GRO-α can influence both the migration and fate choice of SVZ-derived neural precursor cells, as well as promoting cell viability. While a response to each of these chemokines is maintained in the middle-aged brain, a distinct age-related alteration in differential fate can be identified.

  8. Toward Defining the Neural Substrates of ADHD: A Controlled Structural MRI Study in Medication-Naïve Adults

    PubMed Central

    Makris, Nikos; Liang, Lichen; Biederman, Joseph; Valera, Eve M.; Brown, Ariel B.; Petty, Carter; Spencer, Thomas J.; Faraone, Stephen V.; Seidman, Larry J.

    2014-01-01

    Objective We assessed the neural correlates of adult ADHD in treatment-naïve participants, an approach necessary for identifying neural substrates unconfounded by medication effects. Method The sample consisted of 24 medication-naïve adults with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnosed ADHD and 24 healthy controls, comparable on age, sex, handedness, reading achievement, IQ, and psychiatric comorbidity. All participants were assessed with structured diagnostic interviews. Magnetic resonance imaging (MRI)-based regional voxel-based morphometry (r-VBM) was used to assess volumetric differences in a priori defined brain regions of interest. Results VBM analysis revealed group differences in the hypothesized cortical and subcortical areas; however, only cerebellar volume reductions in ADHD retained significance (p < .05) after corrections for multiple comparisons. Conclusion These results support the notion that medication-naïve ADHD as expressed in adulthood, manifests subtle brain volume reductions from normal in the cerebellum, and possibly in other syndrome-congruent gray-matter structures. Larger samples are required to confirm these findings. PMID:24189200

  9. A virtual water maze revisited: Two-year changes in navigation performance and their neural correlates in healthy adults.

    PubMed

    Daugherty, Ana M; Raz, Naftali

    2017-02-01

    Age-related declines in spatial navigation are associated with deficits in procedural and episodic memory and deterioration of their neural substrates. For the lack of longitudinal evidence, the pace and magnitude of these declines and their neural mediators remain unclear. Here we examined virtual navigation in healthy adults (N=213, age 18-77 years) tested twice, two years apart, with complementary indices of navigation performance (path length and complexity) measured over six learning trials at each occasion. Slopes of skill acquisition curves and longitudinal change therein were estimated in structural equation modeling, together with change in regional brain volumes and iron content (R2* relaxometry). Although performance on the first trial did not differ between occasions separated by two years, the slope of path length improvement over trials was shallower and end-of-session performance worse at follow-up. Advanced age, higher pulse pressur