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Sample records for adult cortical plasticity

  1. 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

  2. A cortical disinhibitory circuit for enhancing adult plasticity

    PubMed Central

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

    2015-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.05558.001 PMID:25626167

  3. The role of sound in adult and developmental auditory cortical plasticity.

    PubMed

    Eggermont, Jos J

    2008-12-01

    The purpose of the current review is to highlight the role of the acoustic environment in auditory cortical plasticity. In order do this we have reviewed our past studies on auditory cortical plasticity based on long-latency evoked potential recordings in humans following cochlear implantation, and multiple single-unit recordings from cat auditory cortex following noise trauma and exposure to a non-deafening acoustic environment. The results of these studies, and those of other investigators highlighted here, show that the auditory cortex shows plastic changes throughout life. Those that occur during maturation are typically considered the most profound and long lasting. In that case plasticity is beneficial as it allows adaptation to behaviorally important sound and adapts easily to changes induced by deafness and subsequent application of hearing aids or cochlear implants. In children as well as adults, changes in cortical representation of frequency can occur following hearing loss, but may be accompanied by unpleasant side effects such as tinnitus. Long exposure to a spectrally enhanced acoustic environment of moderate sound level that does not cause hearing loss paradoxically also results in pronounced changes in the cortical tonotopic maps. These changes are very similar to those following noise trauma. This review provides evidence that in adults, long-lasting plastic changes in auditory cortex occur even in the absence of behaviorally relevant acoustic stimulation. However, in children, the long lasting absence of auditory stimulation arrests cortical development.

  4. Adult cortical plasticity studied with chronically implanted electrode arrays.

    PubMed

    Abe, Hiroshi; McManus, Justin N J; Ramalingam, Nirmala; Li, Wu; Marik, Sally A; Borgloh, Stephan Meyer Zum Alten; Gilbert, Charles D

    2015-02-11

    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.

  5. 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

  6. 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. PMID:26663520

  7. Cortical plasticity and rehabilitation.

    PubMed

    Moucha, Raluca; Kilgard, Michael P

    2006-01-01

    The brain is constantly adapting to environmental and endogenous changes (including injury) that occur at every stage of life. The mechanisms that regulate neural plasticity have been refined over millions of years. Motivation and sensory experience directly shape the rewiring that makes learning and neurological recovery possible. Guiding neural reorganization in a manner that facilitates recovery of function is a primary goal of neurological rehabilitation. As the rules that govern neural plasticity become better understood, it will be possible to manipulate the sensory and motor experience of patients to induce specific forms of plasticity. This review summarizes our current knowledge regarding factors that regulate cortical plasticity, illustrates specific forms of reorganization induced by control of each factor, and suggests how to exploit these factors for clinical benefit.

  8. Intermanual transfer and bilateral cortical plasticity is maintained in older adults after skilled motor training with simple and complex tasks

    PubMed Central

    Dickins, Daina S. E.; Sale, Martin V.; Kamke, Marc R.

    2015-01-01

    Intermanual transfer refers to the phenomenon whereby unilateral motor training induces performance gains in both the trained limb and in the opposite, untrained limb. Evidence indicates that intermanual transfer is attenuated in older adults following training on a simple ballistic movement task, but not after training on a complex task. This study investigated whether differences in plasticity in bilateral motor cortices underlie these differential intermanual transfer effects in older adults. Twenty young (<35 years-old) and older adults (>65 years) trained on a simple (repeated ballistic thumb abduction) and complex (sequential finger-thumb opposition) task in separate sessions. Behavioral performance was used to quantify intermanual transfer between the dominant (trained) and non-dominant (untrained) hands. The amplitude of motor-evoked potentials induced by single pulse transcranial magnetic stimulation was used to investigate excitability changes in bilateral motor cortices. Contrary to predictions, both age groups exhibited performance improvements in both hands after unilateral skilled motor training with simple and complex tasks. These performance gains were accompanied by bilateral increases in cortical excitability in both groups for the simple but not the complex task. The findings suggest that advancing age does not necessarily influence the capacity for intermanual transfer after training with the dominant hand. PMID:25999856

  9. Behavioral recovery and anatomical plasticity in adult rats after cortical lesion and treatment with monoclonal antibody IN-1.

    PubMed

    Emerick, April J; Kartje, Gwendolyn L

    2004-07-01

    We have previously reported that monoclonal antibody (mAb) IN-1 treatment after ischemic infarct in adult rats results in significant recovery of skilled forelimb use. Such recovery was correlated with axonal outgrowth from the intact, opposite motor cortex into deafferented subcortical motor areas. In the present study, we investigated the effects of mAb IN-1 treatment after adult sensorimotor cortex (SMC) aspiration lesion on behavioral recovery and neuroanatomical plasticity in the corticospinal tract. Adult rats underwent unilateral SMC aspiration lesion and treatment with either mAb IN-1 or a control Ab, or no treatment. Animals were then tested over a 6-week period in the skilled forelimb use task and the skilled ladder rung walking task. We found that animals treated with mAb IN-1 after SMC lesion fully recovered the use of forelimb reaching, but showed no improvement in digit grasping as tested in the skilled forelimb use task. The mAb IN-1 treatment group was also significantly improved as compared to control groups in the skilled ladder rung walking test. Furthermore, neuroanatomical tracing revealed a significant increase in the corticospinal projections into the deafferented motor areas of the spinal cord after mAb IN-1 treatment. These results indicate that treatment with mAb IN-1 after cortical aspiration lesion induces remodeling of motor pathways resulting in recovery in only certain behavioral tasks, suggesting that the cause of brain damage influences behavioral recovery after mAb IN-1 treatment. PMID:15196799

  10. Sleep and olfactory cortical plasticity

    PubMed Central

    Barnes, Dylan C.; Wilson, Donald A.

    2014-01-01

    In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders. PMID:24795585

  11. Cortical Magnification Plus Cortical Plasticity Equals Vision?

    PubMed Central

    Born, Richard T.; Trott, Alexander; Hartmann, Till

    2014-01-01

    Most approaches to visual prostheses have focused on the retina, and for good reasons. The earlier that one introduces signals into the visual system, the more one can take advantage of its prodigious computational abilities. For methods that make use of microelectrodes to introduce electrical signals, however, the limited density and volume occupying nature of the electrodes place severe limits on the image resolution that can be provided to the brain. In this regard, non-retinal areas in general, and the primary visual cortex in particular, possess one large advantage: “magnification factor” (MF)—a value that represents the distance across a sheet of neurons that represents a given angle of the visual field. In the foveal representation of primate primary visual cortex, the MF is enormous—on the order of 15–20 mm/deg in monkeys and humans, whereas on the retina, the MF is limited by the optical design of the eye to around 0.3 mm/deg. This means that, for an electrode array of a given density, a much higher- resolution image can be introduced into V1 than onto the retina (or any other visual structure). In addition to this tremendous advantage in resolution, visual cortex is plastic at many different levels ranging from a very local ability to learn to better detect electrical stimulation to higher levels of learning that permit human observers to adapt to radical changes to their visual inputs. We argue that the combination of the large magnification factor and the impressive ability of the cerebral cortex to learn to recognize arbitrary patterns, might outweigh the disadvantages of bypassing earlier processing stages and makes V1 a viable option for the restoration of vision. PMID:25449335

  12. Motor cortical plasticity in Parkinson's disease.

    PubMed

    Udupa, Kaviraja; Chen, Robert

    2013-09-04

    In Parkinson's disease (PD), there are alterations of the basal ganglia (BG) thalamocortical networks, primarily due to degeneration of nigrostriatal dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1), which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS) have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity protocol used, medication, and stimulation status in patients treated with deep brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g., brain derived neurotropic factor and other neurotransmitters or receptors polymorphism), emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic, and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.

  13. Assortment of GABAergic plasticity in the cortical interneuron melting pot.

    PubMed

    Méndez, Pablo; Bacci, Alberto

    2011-01-01

    Cortical structures of the adult mammalian brain are characterized by a spectacular diversity of inhibitory interneurons, which use GABA as neurotransmitter. GABAergic neurotransmission is fundamental for integrating and filtering incoming information and dictating postsynaptic neuronal spike timing, therefore providing a tight temporal code used by each neuron, or ensemble of neurons, to perform sophisticated computational operations. However, the heterogeneity of cortical GABAergic cells is associated to equally diverse properties governing intrinsic excitability as well as strength, dynamic range, spatial extent, anatomical localization, and molecular components of inhibitory synaptic connections that they form with pyramidal neurons. Recent studies showed that similarly to their excitatory (glutamatergic) counterparts, also inhibitory synapses can undergo activity-dependent changes in their strength. Here, some aspects related to plasticity and modulation of adult cortical and hippocampal GABAergic synaptic transmission will be reviewed, aiming at providing a fresh perspective towards the elucidation of the role played by specific cellular elements of cortical microcircuits during both physiological and pathological operations.

  14. Plasticity of Cortical Excitatory-Inhibitory Balance

    PubMed Central

    Froemke, Robert C.

    2015-01-01

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior. PMID:25897875

  15. Inhibitory interneurons in visual cortical plasticity.

    PubMed

    van Versendaal, Daniëlle; Levelt, Christiaan N

    2016-10-01

    For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a temporary decrease in inhibition is essential for plasticity to take place. Here, we discuss how different interneuron subsets regulate plasticity during different stages of cortical maturation. We propose a theory in which different interneuron subsets select the sources of neuronal input that undergo plasticity.

  16. Cortical Plasticity after Cochlear Implantation

    PubMed Central

    Petersen, B.; Gjedde, A.; Wallentin, M.; Vuust, P.

    2013-01-01

    The most dramatic progress in the restoration of hearing takes place in the first months after cochlear implantation. To map the brain activity underlying this process, we used positron emission tomography at three time points: within 14 days, three months, and six months after switch-on. Fifteen recently implanted adult implant recipients listened to running speech or speech-like noise in four sequential PET sessions at each milestone. CI listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech-like stimuli, unlike CI listeners with prelingual hearing loss. Furthermore, Broca's area was activated as an effect of time, but only in CI listeners with postlingual hearing loss. The study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss. Speech processing in patients whose hearing loss occurred after the acquisition of language involves brain areas associated with speech comprehension, which is not the case for patients whose hearing loss occurred before the acquisition of language. Finally, the findings confirm the key role of Broca's area in restoration of speech perception, but only in individuals in whom Broca's area has been active prior to the loss of hearing. PMID:24377050

  17. Cortical plasticity after cochlear implantation.

    PubMed

    Petersen, B; Gjedde, A; Wallentin, M; Vuust, P

    2013-01-01

    The most dramatic progress in the restoration of hearing takes place in the first months after cochlear implantation. To map the brain activity underlying this process, we used positron emission tomography at three time points: within 14 days, three months, and six months after switch-on. Fifteen recently implanted adult implant recipients listened to running speech or speech-like noise in four sequential PET sessions at each milestone. CI listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech-like stimuli, unlike CI listeners with prelingual hearing loss. Furthermore, Broca's area was activated as an effect of time, but only in CI listeners with postlingual hearing loss. The study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss. Speech processing in patients whose hearing loss occurred after the acquisition of language involves brain areas associated with speech comprehension, which is not the case for patients whose hearing loss occurred before the acquisition of language. Finally, the findings confirm the key role of Broca's area in restoration of speech perception, but only in individuals in whom Broca's area has been active prior to the loss of hearing. PMID:24377050

  18. Cortical plasticity after cochlear implantation.

    PubMed

    Petersen, B; Gjedde, A; Wallentin, M; Vuust, P

    2013-01-01

    The most dramatic progress in the restoration of hearing takes place in the first months after cochlear implantation. To map the brain activity underlying this process, we used positron emission tomography at three time points: within 14 days, three months, and six months after switch-on. Fifteen recently implanted adult implant recipients listened to running speech or speech-like noise in four sequential PET sessions at each milestone. CI listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech-like stimuli, unlike CI listeners with prelingual hearing loss. Furthermore, Broca's area was activated as an effect of time, but only in CI listeners with postlingual hearing loss. The study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss. Speech processing in patients whose hearing loss occurred after the acquisition of language involves brain areas associated with speech comprehension, which is not the case for patients whose hearing loss occurred before the acquisition of language. Finally, the findings confirm the key role of Broca's area in restoration of speech perception, but only in individuals in whom Broca's area has been active prior to the loss of hearing.

  19. Experience dependent plasticity alters cortical synchronization

    PubMed Central

    Kilgard, M.P.; Vazquez, J.L.; Engineer, N.D.; Pandya, P.K.

    2008-01-01

    Theories of temporal coding by cortical neurons are supported by observations that individual neurons can respond to sensory stimulation with millisecond precision and that activity in large populations is often highly correlated. Synchronization is highest between neurons with overlapping receptive fields and modulated by both sensory stimulation and behavioral state. It is not yet clear whether cortical synchronization is an epiphenomenon or a critical component of efficient information transmission. Experimental manipulations that generate receptive field plasticity can be used to test the relationship between synchronization and receptive fields. Here we demonstrate that increasing receptive field size in primary auditory cortex by repeatedly pairing a train of tones with nucleus basalis (NB) stimulation increases synchronization, and decreasing receptive field size by pairing different tone frequencies with NB stimulation decreases synchronization. These observations seem to support the conclusion that neural synchronization is simply an artifact caused by common inputs. However, pairing tone trains of different carrier frequencies with NB stimulation increases receptive field size without increasing synchronization, and environmental enrichment increases synchronization without increasing receptive field size. The observation that receptive fields and synchronization can be manipulated independently suggests that common inputs are only one of many factors shaping the strength and temporal precision of cortical synchronization and supports the hypothesis that precise neural synchronization contributes to sensory information processing. PMID:17317055

  20. Music and learning-induced cortical plasticity.

    PubMed

    Pantev, Christo; Ross, Bernhard; Fujioka, Takkao; Trainor, Laurel J; Schulte, Michael; Schulz, Matthias

    2003-11-01

    Auditory stimuli are encoded by frequency-tuned neurons in the auditory cortex. There are a number of tonotopic maps, indicating that there are multiple representations, as in a mosaic. However, the cortical organization is not fixed due to the brain's capacity to adapt to current requirements of the environment. Several experiments on cerebral cortical organization in musicians demonstrate an astonishing plasticity. We used the MEG technique in a number of studies to investigate the changes that occur in the human auditory cortex when a skill is acquired, such as when learning to play a musical instrument. We found enlarged cortical representation of tones of the musical scale as compared to pure tones in skilled musicians. Enlargement was correlated with the age at which musicians began to practice. We also investigated cortical representations for notes of different timbre (violin and trumpet) and found that they are enhanced in violinists and trumpeters, preferentially for the timbre of the instrument on which the musician was trained. In recent studies we extended these findings in three ways. First, we show that we can use MEG to measure the effects of relatively short-term laboratory training involving learning to perceive virtual instead of spectral pitch and that the switch to perceiving virtual pitch is manifested in the gamma band frequency. Second, we show that there is cross-modal plasticity in that when the lips of trumpet players are stimulated (trumpet players assess their auditory performance by monitoring the position and pressure of their lips touching the mouthpiece of their instrument) at the same time as a trumpet tone, activation in the somatosensory cortex is increased more than it is during the sum of the separate lip and trumpet tone stimulation. Third, we show that musicians' automatic encoding and discrimination of pitch contour and interval information in melodies are specifically enhanced compared to those in nonmusicians in that

  1. Cortical Auditory Deafferentation Induces Long-Term Plasticity in the Inferior Colliculus of Adult Rats: Microarray and qPCR Analysis

    PubMed Central

    Clarkson, Cheryl; Herrero-Turrión, M. Javier; Merchán, Miguel A.

    2012-01-01

    The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration rather than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth, and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation, and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs. PMID:23233834

  2. Cortical plasticity associated with Braille learning.

    PubMed

    Hamilton, R H; Pascual-Leone, A

    1998-05-01

    Blind subjects who learn to read Braille must acquire the ability to extract spatial information from subtle tactile stimuli. In order to accomplish this, neuroplastic changes appear to take place. During Braille learning, the sensorimotor cortical area devoted to the representation of the reading finger enlarges. This enlargement follows a two-step process that can be demonstrated with transcranial magnetic stimulation mapping and suggests initial unmasking of existing connections and eventual establishment of more stable structural changes. In addition, Braille learning appears to be associated with the recruitment of parts of the occipital, formerly `visual', cortex (V1 and V2) for tactile information processing. In blind, proficient Braille readers, the occipital cortex can be shown not only to be associated with tactile Braille reading but also to be critical for reading accuracy. Recent studies suggest the possibility of applying non-invasive neurophysiological techniques to guide and improve functional outcomes of these plastic changes. Such interventions might provide a means of accelerating functional adjustment to blindness.

  3. Structural plasticity of circuits in cortical neuropil

    PubMed Central

    Escobar, Gina; Fares, Tarec; Stepanyants, Armen

    2009-01-01

    Learning and memory formation in the brain depend on the plasticity of neural circuits. In the adult and developing cerebral cortex, this plasticity can result from the formation and elimination of dendritic spines. New synaptic contacts appear in the neuropil where the gaps between axonal and dendritic branches can be bridged by dendritic spines. Such sites are termed potential synapses. Here, we describe a theoretical framework for the analysis of spine remodeling plasticity. We provide a quantitative description of two models of spine remodeling in which the presence of a bouton is either required or not for the formation of a new synapse. We derive expressions for the density of potential synapses in the neuropil, the connectivity fraction, which is the ratio of actual to potential synapses, and the number of structurally different circuits attainable with spine remodeling. We calculate these parameters in mouse occipital cortex, rat CA1, monkey V1, and human temporal cortex. We find that on average a dendritic spine can choose among 4–7 potential targets in rodents and 10–20 potential targets in primates. The neuropil’s potential for structural circuit remodeling is highest in rat CA1 (7.1–8.6 bits/µm3) and lowest in monkey V1 (1.3–1.5 bits/µm3). We also evaluate the lower bound of neuron selectivity in the choice of synaptic partners. Post-synaptic excitatory neurons in rodents make synaptic contacts with more than 21–30% of pre-synaptic axons encountered with new spine growth. Primate neurons appear to be more selective, making synaptic connections with more than 7–15% of encountered axons. PMID:18716206

  4. Subplate Neurons: Crucial Regulators of Cortical Development and Plasticity

    PubMed Central

    Kanold, Patrick O.

    2009-01-01

    The developing cerebral cortex contains a distinct class of cells, subplate neurons, which form one of the first functional cortical circuits. Subplate neurons reside in the cortical white matter, receive thalamic inputs and project into the developing cortical plate, mostly to layer 4. Subplate neurons are present at key time points during development. Removal of subplate neurons profoundly affects cortical development. Subplate removal in visual cortex prevents the maturation of thalamocortical synapse, the maturation of inhibition in layer 4, the development of orientation selective responses in individual cortical neurons, and the formation of ocular dominance columns. In addition, monocular deprivation during development reveals that ocular dominance plasticity is paradoxical in the absence of subplate neurons. Because subplate neurons projecting to layer 4 are glutamatergic, these diverse deficits following subplate removal were hypothesized to be due to lack of feed-forward thalamic driven cortical excitation. A computational model of the developing thalamocortical pathway incorporating feed-forward excitatory subplate projections replicates both normal development and plasticity of ocular dominance as well as the effects of subplate removal. Therefore, we postulate that feed-forward excitatory projections from subplate neurons into the developing cortical plate enhance correlated activity between thalamus and layer 4 and, in concert with Hebbian learning rules in layer 4, allow maturational and plastic processes in layer 4 to commence. Thus subplate neurons are a crucial regulator of cortical development and plasticity, and damage to these neurons might play a role in the pathology of many neurodevelopmental disorders. PMID:19738926

  5. 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…

  6. Plasticity of spatial hearing: behavioural effects of cortical inactivation

    PubMed Central

    Nodal, Fernando R; Bajo, Victoria M; King, Andrew J

    2012-01-01

    The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol-Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach-to-target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach-to-target responses to brief sounds (40 ms noise bursts) was reduced by muscimol-Elvax but not by drug-free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience-induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach-to-target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher-level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex. PMID:22547635

  7. Otx2-PNN Interaction to Regulate Cortical Plasticity.

    PubMed

    Bernard, Clémence; Prochiantz, Alain

    2016-01-01

    The ability of the environment to shape cortical function is at its highest during critical periods of postnatal development. In the visual cortex, critical period onset is triggered by the maturation of parvalbumin inhibitory interneurons, which gradually become surrounded by a specialized glycosaminoglycan-rich extracellular matrix: the perineuronal nets. Among the identified factors regulating cortical plasticity in the visual cortex, extracortical homeoprotein Otx2 is transferred specifically into parvalbumin interneurons and this transfer regulates both the onset and the closure of the critical period of plasticity for binocular vision. Here, we review the interaction between the complex sugars of the perineuronal nets and homeoprotein Otx2 and how this interaction regulates cortical plasticity during critical period and in adulthood.

  8. Otx2-PNN Interaction to Regulate Cortical Plasticity

    PubMed Central

    Bernard, Clémence; Prochiantz, Alain

    2016-01-01

    The ability of the environment to shape cortical function is at its highest during critical periods of postnatal development. In the visual cortex, critical period onset is triggered by the maturation of parvalbumin inhibitory interneurons, which gradually become surrounded by a specialized glycosaminoglycan-rich extracellular matrix: the perineuronal nets. Among the identified factors regulating cortical plasticity in the visual cortex, extracortical homeoprotein Otx2 is transferred specifically into parvalbumin interneurons and this transfer regulates both the onset and the closure of the critical period of plasticity for binocular vision. Here, we review the interaction between the complex sugars of the perineuronal nets and homeoprotein Otx2 and how this interaction regulates cortical plasticity during critical period and in adulthood. PMID:26881132

  9. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation.

    PubMed

    Phan, Mimi L; Bieszczad, Kasia M

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded.

  10. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    PubMed Central

    Phan, Mimi L.; Bieszczad, Kasia M.

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID:26881129

  11. Brief dark exposure restored ocular dominance plasticity in aging mice and after a cortical stroke.

    PubMed

    Stodieck, Sophia Katharina; Greifzu, Franziska; Goetze, Bianka; Schmidt, Karl-Friedrich; Löwel, Siegrid

    2014-12-01

    In the primary visual cortex (V1), monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons towards the open eye (Wiesel and Hubel, 1963; Gordon and Stryker, 1996). In V1 of C57Bl/6J mice, this OD-plasticity is maximal in juveniles, declines in adults and is absent beyond postnatal day (PD) 110 (Lehmann and Löwel, 2008) if mice are raised in standard cages. Since it was recently shown that brief dark exposure (DE) restored OD-plasticity in young adult rats (PD70-100) (He et al., 2006), we wondered whether DE would restore OD-plasticity also in adult and old mice and after a cortical stroke. To this end, we raised mice in standard cages until adulthood and transferred them to a darkroom for 10-14 days. Using intrinsic signal optical imaging we demonstrate that short-term DE can restore OD-plasticity after MD in both adult (PD138) and old mice (PD535), and that OD-shifts were mediated by an increase of open eye responses in V1. Interestingly, restored OD-plasticity after DE was accompanied by a reduction of both parvalbumin expressing cells and perineuronal nets and was prevented by increasing intracortical inhibition with diazepam. DE also maintained OD-plasticity in adult mice (PD150) after a stroke in the primary somatosensory cortex. In contrast, short-term DE did not affect basic visual parameters as measured by optomotry. In conclusion, short-term DE was able to restore OD-plasticity in both adult and aging mice and even preserved plasticity after a cortical stroke, most likely mediated by reducing intracortical inhibition.

  12. Metabotropic Glutamate Receptor Dependent Cortical Plasticity in Chronic Pain.

    PubMed

    Koga, Kohei; Li, Shermaine; Zhuo, Min

    2016-01-01

    Many cortical areas play crucial roles in higher order brain functions such as pain and emotion-processing, decision-making, and cognition. Among them, anterior cingulate cortex (ACC) and insular cortex (IC) are two key areas. Glutamate mediates major excitatory transmission during long-term plasticity in both physiological and pathological conditions. Specifically related to nociceptive or pain behaviors, metabotropic glutamate subtype receptors (mGluRs) have been involved in different types of synaptic modulation and plasticity from periphery to the spinal cord. However, less is known about their functional roles in plasticity related to pain and its related behaviors within cortical regions. In this review, we first summarized previous studies of synaptic plasticity in both the ACC and IC, and discussed how mGluRs may be involved in both cortical long-term potentiation (LTP) and long-term depression (LTD)-especially in LTD. The activation of mGluRs contributes to the induction of LTD in both ACC and IC areas. The loss of LTD caused by peripheral amputation or nerve injury can be rescued by priming ACC or IC with activations of mGluR1 receptors. We also discussed the potential functional roles of mGluRs for pain-related behaviors. We propose that targeting mGluRs in the cortical areas including the ACC and IC may provide a new therapeutic strategy for the treatment of chronic pain, phantom pain or anxiety. PMID:27296638

  13. Prolonged period of cortical plasticity upon redox dysregulation in fast-spiking interneurons

    PubMed Central

    Morishita, Hirofumi; Cabungcal, Jan-Harry; Chen, Ying; Do, Kim Q.; Hensch, Takao K.

    2015-01-01

    Background Oxidative stress and the specific impairment of peri-somatic GABA circuits are hallmarks of the schizophrenic brain and its animal models. Proper maturation of these fast-spiking inhibitory interneurons normally defines critical periods of experience-dependent cortical plasticity. Method Here, we link these processes by genetically inducing a redox dysregulation restricted to such parvalbumin-positive cells and examined the impact on critical period plasticity using the visual system as a model (3–6mice/group). Results Oxidative stress was accompanied by a significant loss of perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult plasticity. Accordingly, the neocortex remained plastic even beyond the peak of its natural critical period. These effects were not seen when redox dysregulation was targeted in excitatory principal cells. Conclusion A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mis-timed developmental trajectories of brain plasticity may underlie in part the pathophysiology of mental illness. Such prolonged developmental plasticity may in turn offer a therapeutic opportunity for cognitive interventions targeting brain plasticity in schizophrenia. PMID:25758057

  14. Dynamic Plasticity of Coupled Cortical Maps

    NASA Astrophysics Data System (ADS)

    Atwal, G. S.

    2003-03-01

    Spatiotemporal location of an object may be achieved by inference from a combination of different noisy stimuli such as in the case of barn owls which locate prey using both aural and visual stimuli. The symbolic representation of an event is carried out using the receptive fields of neurons in the cortex, and in a normal barn owl the aural and visual receptive fields are aligned from early experiences. However, misalignment induced by the wearing of prismatic glasses may result in adaptive behavior, manifested by physical modification of the receptive fields. A model of this dynamic plasticity is presented and analyzed by maximising the weighted information of both sensory neural outputs, demonstrating a transition from adaptive to non-adaptive behavior as the rate of misalignment increases.

  15. Mechanisms of sleep-dependent consolidation of cortical plasticity

    PubMed Central

    Aton, Sara J.; Seibt, Julie; Dumoulin, Michelle; Jha, Sushil K.; Steinmetz, Nicholas; Coleman, Tammi; Naidoo, Nirinjini; Frank, Marcos G.

    2009-01-01

    Summary Sleep is thought to consolidate changes in synaptic strength, but the underlying mechanisms are unknown. We investigated the cellular events involved in this process in ocular dominance plasticity (ODP) - a canonical form of in vivo cortical plasticity triggered by monocular deprivation (MD) and consolidated by sleep via undetermined, activity-dependent mechanisms. We find that sleep consolidates ODP primarily by strengthening cortical responses to non-deprived eye stimulation. Consolidation is inhibited by reversible, intracortical antagonism of NMDA receptors (NMDARs) or cAMP-dependent protein kinase (PKA) during post-MD sleep. Consolidation is also associated with sleep-dependent increases in the activity of remodeling neurons, and in the phosphorylation of proteins required for potentiation of glutamatergic synapses. These findings demonstrate that synaptic strengthening via NMDAR and PKA activity is a key step in sleep-dependent consolidation of ODP. PMID:19217381

  16. Bidirectional plasticity of cortical pattern recognition and behavioral sensory acuity

    PubMed Central

    Chapuis, Julie; Wilson, Donald A.

    2011-01-01

    Learning to adapt to a complex and fluctuating environment requires the ability to adjust neural representations of sensory stimuli. Through pattern completion processes, cortical networks can reconstruct familiar patterns from degraded input patterns, while pattern separation processes allow discrimination of even highly overlapping inputs. Here we show that the balance between pattern separation and completion is experience-dependent. Rats given extensive training with overlapping complex odorant mixtures show improved behavioral discrimination ability and enhanced cortical ensemble pattern separation. In contrast, behavioral training to disregard normally detectable differences between overlapping mixtures results in impaired cortical ensemble pattern separation (enhanced pattern completion) and impaired discrimination. This bidirectional effect was not found in the olfactory bulb, and may be due to plasticity within olfactory cortex itself. Thus pattern recognition, and the balance between pattern separation and completion, is highly malleable based on task demands and occurs in concert with changes in perceptual performance. PMID:22101640

  17. Cortical Plasticity, Excitatory–Inhibitory Balance, and Sensory Perception

    PubMed Central

    Carcea, Ioana; Froemke, Robert C.

    2015-01-01

    Experience shapes the central nervous system throughout life. Structural and functional plasticity confers a remarkable ability on the brain, allowing neural circuits to adequately adapt to dynamic environments. This process can require selective adjustment of many excitatory and inhibitory synapses in an organized manner, in such a way as to enhance representations of behaviorally important sensory stimuli while preserving overall network excitability. The rules and mechanisms that orchestrated these changes across different synapses and throughout neuronal ensembles are beginning to be understood. Here, we review the evidence connecting synaptic plasticity to functional plasticity and perceptual learning, focusing on the roles of various neuromodulatory systems in enabling plasticity of adult neural circuits. However, the challenge remains to appropriately leverage these systems and forms of plasticity to persistently improve perceptual abilities and behavioral performance. PMID:24309251

  18. Auditory-somatosensory integration and cortical plasticity in musical training.

    PubMed

    Pantev, Christo; Lappe, Claudia; Herholz, Sibylle C; Trainor, Laurel

    2009-07-01

    Learning to play a musical instrument requires complex multimodal skills involving simultaneous perception of several sensory modalities: auditory, visual, and somatosensory as well as the motor system. Musical training thus provides an adequate neuroscientific model to study multimodal integration and plasticity in musical training. The aim of this study was to investigate the impact of short-term uni- and multimodal musical training on auditory-somatosensory integration and plasticity. Two groups of nonmusicians were musically trained. The first group (sensorimotor-auditory group, SA) learned to play a musical sequence on the piano, whereas the second one (auditory group, A) actively listened to and made judgments about the correctness of the music. The training-induced cortical plasticity effect was assessed by recording musically elicited mismatch negativity (MMN) from magnetoencephalographic (MEG) measurements before and after training. The SA group showed significant enlargement of MMN after training compared to the A group, reflecting greater enhancement of musical representations in auditory cortex after sensorimotor-auditory training compared to mere auditory training. This study demonstrates that the sensorimotor and auditory systems integrate and that this multimodal training causes cortical reorganizational changes in the auditory cortex over and above the changes introduced by auditory training alone.

  19. Brain Plasticity in Blind Subjects Centralizes Beyond the Modal Cortices

    PubMed Central

    Ortiz-Terán, Laura; Ortiz, Tomás; Perez, David L.; Aragón, Jose Ignacio; Diez, Ibai; Pascual-Leone, Alvaro; Sepulcre, Jorge

    2016-01-01

    It is well established that the human brain reorganizes following sensory deprivations. In blind individuals, visual processing regions including the lateral occipital cortex (LOC) are activated by auditory and tactile stimuli as demonstrated by neurophysiological and neuroimaging investigations. The mechanisms for such plasticity remain unclear, but shifts in connectivity across existing neural networks appear to play a critical role. The majority of research efforts to date have focused on neuroplastic changes within visual unimodal regions, however we hypothesized that neuroplastic alterations may also occur in brain networks beyond the visual cortices including involvement of multimodal integration regions and heteromodal cortices. In this study, two recently developed graph-theory based functional connectivity analyses, interconnector analyses and local and distant connectivity, were applied to investigate functional reorganization in regional and distributed neural-systems in late-onset blind (LB) and congenitally blind (CB) cohorts each compared to their own group of sighted controls. While functional network alterations as measured by the degree of differential links (DDL) occurred in sensory cortices, neuroplastic changes were most prominent within multimodal and association cortices. Subjects with LB showed enhanced multimodal integration connections in the parieto-opercular, temporoparietal junction (TPJ) and ventral premotor (vPM) regions, while CB individuals exhibited increased superior parietal cortex (SPC) connections. This study reveals the critical role of recipient multi-sensory integration areas in network reorganization and cross-modal plasticity in blind individuals. These findings suggest that aspects of cross-modal neuroplasticity and adaptive sensory-motor and auditory functions may potentially occur through reorganization in multimodal integration regions. PMID:27458350

  20. Brain Plasticity in Blind Subjects Centralizes Beyond the Modal Cortices.

    PubMed

    Ortiz-Terán, Laura; Ortiz, Tomás; Perez, David L; Aragón, Jose Ignacio; Diez, Ibai; Pascual-Leone, Alvaro; Sepulcre, Jorge

    2016-01-01

    It is well established that the human brain reorganizes following sensory deprivations. In blind individuals, visual processing regions including the lateral occipital cortex (LOC) are activated by auditory and tactile stimuli as demonstrated by neurophysiological and neuroimaging investigations. The mechanisms for such plasticity remain unclear, but shifts in connectivity across existing neural networks appear to play a critical role. The majority of research efforts to date have focused on neuroplastic changes within visual unimodal regions, however we hypothesized that neuroplastic alterations may also occur in brain networks beyond the visual cortices including involvement of multimodal integration regions and heteromodal cortices. In this study, two recently developed graph-theory based functional connectivity analyses, interconnector analyses and local and distant connectivity, were applied to investigate functional reorganization in regional and distributed neural-systems in late-onset blind (LB) and congenitally blind (CB) cohorts each compared to their own group of sighted controls. While functional network alterations as measured by the degree of differential links (DDL) occurred in sensory cortices, neuroplastic changes were most prominent within multimodal and association cortices. Subjects with LB showed enhanced multimodal integration connections in the parieto-opercular, temporoparietal junction (TPJ) and ventral premotor (vPM) regions, while CB individuals exhibited increased superior parietal cortex (SPC) connections. This study reveals the critical role of recipient multi-sensory integration areas in network reorganization and cross-modal plasticity in blind individuals. These findings suggest that aspects of cross-modal neuroplasticity and adaptive sensory-motor and auditory functions may potentially occur through reorganization in multimodal integration regions. PMID:27458350

  1. Peripheral electrical stimulation to induce cortical plasticity: a systematic review of stimulus parameters.

    PubMed

    Chipchase, L S; Schabrun, S M; Hodges, P W

    2011-03-01

    Peripheral electrical stimulation (ES) is commonly used as an intervention to facilitate movement and relieve pain in a variety of conditions. It is widely accepted that ES induces rapid plastic change in the motor cortex. This leads to the exciting possibility that ES could be used to drive cortical plasticity in movement disorders, such as stroke, and conditions where pain affects motor control. This paper aimed to critically review the literature to determine which parameters induced cortical plasticity in healthy individuals using ES. A literature search located papers that assessed plasticity in the primary motor cortex of adult humans. Studies that evaluated plasticity using change in the amplitude of potentials evoked by transcranial magnetic stimulation of the motor cortex were included. Details from each study including sample size, ES parameters and reported findings were extracted and compared. Where data were available, Cohen's standardised mean differences (SMD) were calculated. Nineteen studies were located. Of the parameters evaluated, variation of the intensity of peripheral ES appeared to have the most consistent effect on modulation of excitability of corticomotor pathway to stimulated muscles. There was a trend for stimulation above motor threshold to increase excitability (SMD 0.79 mV, CI -0.10 to 1.64). Stimulation below motor threshold, but sufficient to induce sensory perception, produced conflicting results. Further studies with consistent methodology and larger subject numbers are needed before definitive conclusions can be drawn. There also appeared to be a time effect. That is, longer periods of ES induced more sustained changes in cortical excitability. There is insufficient evidence to determine the effect of other stimulation parameters such as frequency and waveform. Further research is needed to confirm whether modulation of these parameters affects plastic change. PMID:20739217

  2. Modeling attention-driven plasticity in auditory cortical receptive fields

    PubMed Central

    Carlin, Michael A.; Elhilali, Mounya

    2015-01-01

    To navigate complex acoustic environments, listeners adapt neural processes to focus on behaviorally relevant sounds in the acoustic foreground while minimizing the impact of distractors in the background, an ability referred to as top-down selective attention. Particularly striking examples of attention-driven plasticity have been reported in primary auditory cortex via dynamic reshaping of spectro-temporal receptive fields (STRFs). By enhancing the neural response to features of the foreground while suppressing those to the background, STRFs can act as adaptive contrast matched filters that directly contribute to an improved cognitive segregation between behaviorally relevant and irrelevant sounds. In this study, we propose a novel discriminative framework for modeling attention-driven plasticity of STRFs in primary auditory cortex. The model describes a general strategy for cortical plasticity via an optimization that maximizes discriminability between the foreground and distractors while maintaining a degree of stability in the cortical representation. The first instantiation of the model describes a form of feature-based attention and yields STRF adaptation patterns consistent with a contrast matched filter previously reported in neurophysiological studies. An extension of the model captures a form of object-based attention, where top-down signals act on an abstracted representation of the sensory input characterized in the modulation domain. The object-based model makes explicit predictions in line with limited neurophysiological data currently available but can be readily evaluated experimentally. Finally, we draw parallels between the model and anatomical circuits reported to be engaged during active attention. The proposed model strongly suggests an interpretation of attention-driven plasticity as a discriminative adaptation operating at the level of sensory cortex, in line with similar strategies previously described across different sensory modalities

  3. Experience-dependent plasticity of visual cortical microcircuits.

    PubMed

    Medini, P

    2014-10-10

    The recent decade testified a tremendous increase in our knowledge on how cell-type-specific microcircuits process sensory information in the neocortex and on how such circuitry reacts to manipulations of the sensory environment. Experience-dependent plasticity has now been investigated with techniques endowed with cell resolution during both postnatal development and in adult animals. This review recapitulates the main recent findings in the field using mainly the primary visual cortex as a model system to highlight the more important questions and physiological principles (such as the role of non-competitive mechanisms, the role of inhibition in excitatory cell plasticity, the functional importance of spine and axonal plasticity on a microscale level). I will also discuss on which scientific problems the debate and controversies are more pronounced. New technologies that allow to perturbate cell-type-specific subcircuits will certainly shine new light in the years to come at least on some of the still open questions.

  4. Movement-related cortical stimulation can induce human motor plasticity.

    PubMed

    Thabit, Mohamed Nasreldin; Ueki, Yoshino; Koganemaru, Satoko; Fawi, Gharib; Fukuyama, Hidenao; Mima, Tatsuya

    2010-08-25

    Repeated paired associative stimulation combining peripheral nerve stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can produce human motor plasticity. However, previous studies used paired artificial stimuli, so that it is not known whether repetitive natural M1 activity associated with TMS can induce plasticity or not. To test this hypothesis, we developed a movement-related cortical stimulation (MRCS) protocol, in which the left M1 was stimulated by TMS at specific timing with respect to the mean expected reaction time (RT) of voluntary movement during a simple reaction time task using the right abductor pollicis brevis (APB) muscle. Seventeen normal volunteers were subjected to repeated MRCS intervention (0.2 Hz, 240 pairs). Motor function was assessed before and after MRCS. When TMS was given 50 ms before the RT of movement [MRCS(-50)], motor-evoked potential (MEP) amplitude of the right APB, but not other muscles, increased for up to 15 min post-MRCS. The RT of the right APB was also shortened. However, spinal excitability measured by F-wave did not change. When TMS was given 100 ms after the RT [MRCS(+100)], MEP amplitude was decreased. These findings show that this new MRCS protocol can produce timing-dependent motor associative plasticity, which may be clinically useful.

  5. Inverted-U function relating cortical plasticity and task difficulty.

    PubMed

    Engineer, N D; Engineer, C T; Reed, A C; Pandya, P K; Jakkamsetti, V; Moucha, R; Kilgard, M P

    2012-03-15

    Many psychological and physiological studies with simple stimuli have suggested that perceptual learning specifically enhances the response of primary sensory cortex to task-relevant stimuli. The aim of this study was to determine whether auditory discrimination training on complex tasks enhances primary auditory cortex responses to a target sequence relative to non-target and novel sequences. We collected responses from more than 2000 sites in 31 rats trained on one of six discrimination tasks that differed primarily in the similarity of the target and distractor sequences. Unlike training with simple stimuli, long-term training with complex stimuli did not generate target-specific enhancement in any of the groups. Instead, cortical receptive field size decreased, latency decreased, and paired pulse depression decreased in rats trained on the tasks of intermediate difficulty, whereas tasks that were too easy or too difficult either did not alter or degraded cortical responses. These results suggest an inverted-U function relating neural plasticity and task difficulty.

  6. Inverted-U Function Relating Cortical Plasticity and Task Difficulty

    PubMed Central

    Engineer, Navzer D.; Engineer, Crystal T.; Reed, Amanda C.; Pandya, Pritesh K.; Jakkamsetti, Vikram; Moucha, Raluca; Kilgard, Michael P.

    2012-01-01

    Many psychological and physiological studies with simple stimuli have suggested that perceptual learning specifically enhances the response of primary sensory cortex to task-relevant stimuli. The aim of this study was to determine whether auditory discrimination training on complex tasks enhances primary auditory cortex responses to a target sequence relative to non-target and novel sequences. We collected responses from more than 2,000 sites in 31 rats trained on one of six discrimination tasks that differed primarily in the similarity of the target and distractor sequences. Unlike training with simple stimuli, long-term training with complex stimuli did not generate target specific enhancement in any of the groups. Instead, cortical receptive field size decreased, latency decreased, and paired pulse depression decreased in rats trained on the tasks of intermediate difficulty while tasks that were too easy or too difficult either did not alter or degraded cortical responses. These results suggest an inverted-U function relating neural plasticity and task difficulty. PMID:22249158

  7. Interneuron epigenomes during the critical period of cortical plasticity: Implications for schizophrenia.

    PubMed

    Morishita, Hirofumi; Kundakovic, Marija; Bicks, Lucy; Mitchell, Amanda; Akbarian, Schahram

    2015-10-01

    Schizophrenia, a major psychiatric disorder defined by delusions and hallucinations, among other symptoms, often with onset in early adulthood, is potentially associated with molecular and cellular alterations in parvalbumin-expressing fast spiking interneurons and other constituents of the cortical inhibitory GABAergic circuitry. The underlying mechanisms, including the role of disease-associated risk factors operating in adolescence such as drug abuse and social stressors, remain incompletely understood. Here, we summarize emerging findings from animal models, highlighting the ability of parvalbuminergic interneurons (PVI) to induce, during the juvenile period, long-term plastic changes in prefrontal and visual cortex, thereby altering perception, cognition and behavior in the adult. Of note, molecular alterations in PVI from subjects with schizophrenia, including downregulated expression of a subset of GABAergic genes, have also been found in juvenile stress models of the disorder. Some of the transcriptional alterations observed in schizophrenia postmortem brain could be linked to changes in the epigenetic architecture of GABAergic gene promoters, including dysregulated DNA methylation, histone modification patterns and disruption of promoter-enhancer interactions at site of chromosomal loop formations. Therefore, we predict that, in the not-to-distant future, PVI- and other cell-type specific epigenomic mappings in the animal model and human brain will provide novel insights into the pathophysiology of schizophrenia and related psychotic diseases, including the role of cortical GABAergic circuitry in shaping long-term plasticity and cognitive function of the cerebral cortex.

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

    PubMed Central

    Stryker, Michael P.

    2015-01-01

    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. PMID:25948638

  9. Cortical plasticity in episodic and chronic cluster headache

    PubMed Central

    Naegel, Steffen; Holle, Dagny; Desmarattes, Nathalie; Theysohn, Nina; Diener, Hans-Christoph; Katsarava, Zaza; Obermann, Mark

    2014-01-01

    Cluster headache (CH) is characterized by recurrent episodes of excruciatingly painful, unilateral headache attacks typically accompanied by trigeminal autonomic symptoms. Due to its rhythm with alternating episodes of pain and no-pain, it is an excellent model to investigate whether structural brain changes detected by magnetic resonance based voxel-based-morphometry (VBM) reflect the cause of the disease, may be a consequence of the underlying disease other than pain, or may simply be caused by the sensation of pain itself. We investigated 91 patients with CH in different stages of their disease using VBM and compared them to 78 age- and gender-matched healthy controls. We detected distinct regional gray matter (GM) changes in different brain regions including the temporal lobe, the hippocampus, the insular cortex and the cerebellum. The extent, location and direction of observed GM alterations depended on the state of disease and appeared dynamic in relation to pain state (i.e., pain vs. no-pain). No hypothalamic changes were detected in CH patients compared to healthy controls. The GM changes observed in this study are highly dynamic and thereby reflect the cortical plasticity of the brain in regard to pain. This observed dynamic may provide an explanation of the diverse results of previous VBM studies in pain. Regarding CH the results suggest that the disease is more likely to be caused by a network dysfunction rather than by a single malfunctioning structure. PMID:25379455

  10. 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

  11. Asymmetrical Cortical Processing of Radial Expansioncontraction in Infants and Adults

    ERIC Educational Resources Information Center

    Shirai, Nobu; Birtles, Deirdre; Wattam-Bell, John; Yamaguchi, Masami K.; Kanazawa, So; Atkinson, Janette; Braddick, Oliver

    2009-01-01

    We report asymmetrical cortical responses (steady-state visual evoked potentials) to radial expansion and contraction in human infants and adults. Forty-four infants (22 3-month-olds and 22 4-month-olds) and nine adults viewed dynamic dot patterns which cyclically (2.1 Hz) alternate between radial expansion (or contraction) and random directional…

  12. Adult Astrogenesis and the Etiology of Cortical Neurodegeneration

    PubMed Central

    Mohn, Tal C.; Koob, Andrew O.

    2015-01-01

    As more evidence points to a clear role for astrocytes in synaptic processing, synaptogenesis and cognition, continuing research on astrocytic function could lead to strategies for neurodegenerative disease prevention. Reactive astrogliosis results in astrocyte proliferation early in injury and disease states and is considered neuroprotective, indicating a role for astrocytes in disease etiology. This review describes the different types of human cortical astrocytes and the current evidence regarding adult cortical astrogenesis in injury and degenerative disease. A role for disrupted astrogenesis as a cause of cortical degeneration, with a focus on the tauopathies and synucleinopathies, will also be considered. PMID:26568684

  13. Neural plasticity in adults with amblyopia.

    PubMed Central

    Levi, D M; Polat, U

    1996-01-01

    Amblyopia is a neuronal abnormality of vision that is often considered irreversible in adults. We found strong and significant improvement of Vernier acuity in human adults with naturally occurring amblyopia following practice. Learning was strongest at the trained orientation and did not transfer to an untrained task (detection), but it did transfer partially to the untrained eye (primarily at the trained orientation). We conclude that this perceptual learning reflects alterations in early neural processes that are localized beyond the site of convergence of the two eyes. Our results suggest a significant degree of plasticity in the visual system of adults with amblyopia. PMID:8692904

  14. Thinking outside the brain: structural plasticity in the spinal cord promotes recovery from cortical stroke.

    PubMed

    Tennant, Kelly A

    2014-04-01

    Neuroanatomically connected regions distal to a cortical stroke can exhibit both degenerative and adaptive changes during recovery. As the locus for afferent somatosensory fibres and efferent motor fibres, the spinal cord is ideally situated to play a critical role in functional recovery. In contrast to the wealth of research into cortical plasticity after stroke, much less focus has previously been placed on the role of subcortical or spinal cord plasticity in recovery of function after cortical stroke. Little is known about the extent and spatiotemporal profile of spinal rewiring, its regulation by neurotrophins or inflammatory cytokines, or its potential as a therapeutic target to improve stroke recovery. This commentary examines the recent findings by Sist et al. (2014) that there is a distinct critical period of heightened structural plasticity, growth factor expression, and inflammatory cytokine production in the spinal cord. They suggest that neuroplasticity is highest during the first two weeks after stroke and tapers off dramatically by the fourth week. Spinal cord plasticity correlates with the severity of cortical injury and temporally matches periods of accelerated spontaneous recovery of skilled reaching function. The potential of treatments that extend or re-open this window of spinal cord plasticity, such as anti-Nogo-A antibodies or chondroitinase ABC, to dramatically improve recovery from cortical stroke in clinical populations is discussed.

  15. 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

  16. Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

    PubMed

    Cybulska-Klosowicz, Anita; Mazarakis, Nektarios K; Van Dellen, Anton; Blakemore, Colin; Hannan, Anthony J; Kossut, Malgorzata

    2004-12-01

    Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD. We examined the impact of the HD transgene upon learning-dependent plasticity of cortical representational maps. The effect of associative learning, in which stimulation of a row of vibrissae was paired with appetitive stimulus, upon functional representations of vibrissae in the barrel cortex, was investigated with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type mice, cortical representation of the row of vibrissae involved in the training was expanded, while in HD mice the representation of this row was not expanded. The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in plasticity of primary somatosensory cortex.

  17. Human Adult Cortical Reorganization and Consequent Visual Distortion

    PubMed Central

    Dilks, Daniel D.; Serences, John T.; Rosenau, Benjamin J.; Yantis, Steven; McCloskey, Michael

    2009-01-01

    Neural and behavioral evidence for cortical reorganization in the adult somatosensory system after loss of sensory input (e.g., amputation) has been well documented. In contrast, evidence for reorganization in the adult visual system is far less clear: neural evidence is the subject of controversy, behavioral evidence is sparse, and studies combining neural and behavioral evidence have not previously been reported. Here, we report converging behavioral and neuroimaging evidence from a stroke patient (B.L.) in support of cortical reorganization in the adult human visual system. B.L.’s stroke spared the primary visual cortex (V1), but destroyed fibers that normally provide input to V1 from the upper left visual field (LVF). As a consequence, B.L. is blind in the upper LVF, and exhibits distorted perception in the lower LVF: stimuli appear vertically elongated, toward and into the blind upper LVF. For example, a square presented in the lower LVF is perceived as a rectangle extending upward. We hypothesized that the perceptual distortion was a consequence of cortical reorganization in V1. Extensive behavioral testing supported our hypothesis, and functional magnetic resonance imaging (fMRI) confirmed V1 reorganization. Together, the behavioral and fMRI data show that loss of input to V1 after a stroke leads to cortical reorganization in the adult human visual system, and provide the first evidence that reorganization of the adult visual system affects visual perception. These findings contribute to our understanding of the human adult brain’s capacity to change and has implications for topics ranging from learning to recovery from brain damage. PMID:17804619

  18. Cortical thickness in adults with agenesis of the corpus callosum.

    PubMed

    Beaulé, Vincent; Tremblay, Sara; Lafleur, Louis-Philippe; Tremblay, Sébastien; Lassonde, Maryse; Lepage, Jean-François; Théoret, Hugo

    2015-10-01

    Agenesis of the corpus callosum (AgCC) is a congenital malformation that can occur in isolation or in association with other neurological conditions. Although the behavioral manifestations associated with AgCC have been widely studied, the effects of complete absence of the corpus callosum (CC) on cerebral cortex anatomy are still not completely understood. In this study, cortical thickness in adults with complete AgCC was compared to a group of healthy controls. Results showed highly variable patterns of cortical thickness in AgCC individuals, with few areas showing significant and consistent alterations including primary visual cortex, primary somatosensory cortex and primary motor cortex. These results suggest relatively limited effects of AgCC on cortical morphology, which are mostly restricted to primary sensory and motor areas.

  19. Compressive behaviour of child and adult cortical bone.

    PubMed

    Öhman, Caroline; Baleani, Massimiliano; Pani, Carla; Taddei, Fulvia; Alberghini, Marco; Viceconti, Marco; Manfrini, Marco

    2011-10-01

    In this study, cortical bone tissue from children was investigated. It is extremely difficult to obtain human child tissue. Therefore, the only possibility was to use bone tissue, free from any lesion, collected from young bone cancer patients. The compressive mechanical behaviour of child bone tissue was compared to the behaviour of adult tissue. Moreover, two hypotheses were tested: 1) that the mechanical behaviour of both groups is correlated to ash density; 2) that yield strain is an invariant. Small parts of the diaphysis of femora or tibiae from 12 children (4-15 years) and 12 adults (22-61 years) were collected. Cylindrical specimens were extracted from the cortical wall along the longitudinal axis of the diaphysis. A total of 107 specimens underwent compressive testing (strain rate: 0.1 s(-1)). Only the specimens showing a regular load-displacement curve (94) were considered valid and thereafter reduced to ash. It was found that the child bone tissue had significant lower compressive Young's modulus (-34%), yield stress (-38%), ultimate stress (-33%) and ash density (-17%) than the adult tissue. Conversely, higher compressive ultimate strain was found in the child group (+24%). Despite specimens extracted from both children and adults, ash density largely described the variation in tissue strength and stiffness (R(2)=in the range of 0.86-0.91). Furthermore, yield strain seemed to be roughly an invariant to subject age and tissue density. These results confirm that the mechanical properties of child cortical bone tissue are different from that of adult tissue. However, such differences are correlated to differences in tissue ash density. In fact, ash density was found to be a good predictor of strength and stiffness, also for cortical bone collected from children. Finally, the present findings support the hypothesis that compressive yield strain is an invariant.

  20. Layer-specific cholinergic control of human and mouse cortical synaptic plasticity.

    PubMed

    Verhoog, Matthijs B; Obermayer, Joshua; Kortleven, Christian A; Wilbers, René; Wester, Jordi; Baayen, Johannes C; De Kock, Christiaan P J; Meredith, Rhiannon M; Mansvelder, Huibert D

    2016-01-01

    Individual cortical layers have distinct roles in information processing. All layers receive cholinergic inputs from the basal forebrain (BF), which is crucial for cognition. Acetylcholinergic receptors are differentially distributed across cortical layers, and recent evidence suggests that different populations of BF cholinergic neurons may target specific prefrontal cortical (PFC) layers, raising the question of whether cholinergic control of the PFC is layer dependent. Here we address this issue and reveal dendritic mechanisms by which endogenous cholinergic modulation of synaptic plasticity is opposite in superficial and deep layers of both mouse and human neocortex. Our results show that in different cortical layers, spike timing-dependent plasticity is oppositely regulated by the activation of nicotinic acetylcholine receptors (nAChRs) either located on dendrites of principal neurons or on GABAergic interneurons. Thus, layer-specific nAChR expression allows functional layer-specific control of cortical processing and plasticity by the BF cholinergic system, which is evolutionarily conserved from mice to humans. PMID:27604129

  1. Layer-specific cholinergic control of human and mouse cortical synaptic plasticity

    PubMed Central

    Verhoog, Matthijs B.; Obermayer, Joshua; Kortleven, Christian A.; Wilbers, René; Wester, Jordi; Baayen, Johannes C.; De Kock, Christiaan P. J.; Meredith, Rhiannon M.; Mansvelder, Huibert D.

    2016-01-01

    Individual cortical layers have distinct roles in information processing. All layers receive cholinergic inputs from the basal forebrain (BF), which is crucial for cognition. Acetylcholinergic receptors are differentially distributed across cortical layers, and recent evidence suggests that different populations of BF cholinergic neurons may target specific prefrontal cortical (PFC) layers, raising the question of whether cholinergic control of the PFC is layer dependent. Here we address this issue and reveal dendritic mechanisms by which endogenous cholinergic modulation of synaptic plasticity is opposite in superficial and deep layers of both mouse and human neocortex. Our results show that in different cortical layers, spike timing-dependent plasticity is oppositely regulated by the activation of nicotinic acetylcholine receptors (nAChRs) either located on dendrites of principal neurons or on GABAergic interneurons. Thus, layer-specific nAChR expression allows functional layer-specific control of cortical processing and plasticity by the BF cholinergic system, which is evolutionarily conserved from mice to humans. PMID:27604129

  2. Recovery of cortical binocularity and orientation selectivity after the critical period for ocular dominance plasticity.

    PubMed

    Liao, David S; Krahe, Thomas E; Prusky, Glen T; Medina, Alexandre E; Ramoa, Ary S

    2004-10-01

    Cortical binocularity is abolished by monocular deprivation (MD) during a critical period of development lasting from approximately postnatal day (P) 35 to P70 in ferrets. Although this is one of the best-characterized models of neural plasticity and amblyopia, very few studies have examined the requirements for recovery of cortical binocularity and orientation selectivity of deprived eye responses. Recent studies indicating that different mechanisms regulate loss and recovery of binocularity raise the possibility that different sensitive periods characterize loss and recovery of deprived eye responses. In this report, we have examined whether the potential for recovery of binocularity and orientation selectivity is restricted to the critical period. Quantitative single unit recordings revealed recovery of cortical binocularity and full recovery of orientation selectivity of deprived eye responses following prolonged periods of MD (i.e., >3 wk) starting at P49, near the peak of plasticity. Surprisingly, recovery was present when binocular vision was restored after the end of the critical period for ocular dominance plasticity, as late as P83. In contrast, ferrets that had never received visual experience through the deprived eye failed to recover binocularity even though normal binocular vision was restored at P50, halfway through the critical period. Collectively, these results indicate that there is potential for recovery of cortical binocularity and deprived eye orientation selectivity after the end of the critical period for ocular dominance plasticity.

  3. Cortical Plasticity and Olfactory Function in Early Blindness.

    PubMed

    Araneda, Rodrigo; Renier, Laurent A; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented "visual" cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here. PMID:27625596

  4. Cortical Plasticity and Olfactory Function in Early Blindness

    PubMed Central

    Araneda, Rodrigo; Renier, Laurent A.; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G.

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here. PMID:27625596

  5. Cortical Plasticity and Olfactory Function in Early Blindness

    PubMed Central

    Araneda, Rodrigo; Renier, Laurent A.; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G.

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

  6. Cortical Plasticity and Olfactory Function in Early Blindness.

    PubMed

    Araneda, Rodrigo; Renier, Laurent A; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented "visual" cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

  7. Induction of cortical plasticity for reciprocal muscles by paired associative stimulation

    PubMed Central

    Suzuki, Makoto; Kirimoto, Hikari; Sugawara, Kazuhiro; Watanabe, Makoto; Shimizu, Shinobu; Ishizaka, Ikuyo; Yamada, Sumio; Matsunaga, Atsuhiko; Fukuda, Michinari; Onishi, Hideaki

    2014-01-01

    Background Paired associative stimulation (PAS) is widely used to induce plasticity in the human motor cortex. Although reciprocal inhibition of antagonist muscles plays a fundamental role in human movements, change in cortical circuits for reciprocal muscles by PAS is unknown. Methods We investigated change in cortical plasticity for reciprocal muscles during PAS. PAS consisted of 200 pairs of peripheral electric stimulation of the right median nerve at the wrist at a frequency of 0.25 Hz followed by transcranial magnetic stimulation of the left M1 at the midpoint between the center of gravities of the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Measures of motor cortical excitability included resting motor threshold (RMT), GABAA-mediated short-interval intracortical inhibition (SICI), and GABAB-mediated long-interval intracortical inhibition (LICI). Results Motor evoked potential amplitude-conditioned LICI for the FCR muscle was significantly decreased after PAS (P = 0.020), whereas that for the ECR muscle was significantly increased (P = 0.033). Changes in RMT and SICI for the FCR and ECR muscles were not significantly different before and after PAS. Corticospinal excitability for both reciprocal muscles was increased during PAS, but GABAB-mediated cortical inhibitory functions for the agonist and antagonist muscles were reciprocally altered after PAS. Conclusion These results implied that the cortical excitability for reciprocal muscles including GABAB-ergic inhibitory systems within human M1 could be differently altered by PAS. PMID:25365805

  8. CB1 receptor affects cortical plasticity and response to physiotherapy in multiple sclerosis

    PubMed Central

    Mori, Francesco; Ljoka, Concetta; Nicoletti, Carolina G.; Kusayanagi, Hajime; Buttari, Fabio; Giordani, Laura; Rossi, Silvia; Foti, Calogero

    2014-01-01

    Objectives: Therapeutic effects of physical therapy in neurologic disorders mostly rely on the promotion of use-dependent synaptic plasticity in damaged neuronal circuits. Genetic differences affecting the efficiency of synaptic plasticity mechanisms could explain why some patients do not respond adequately to the treatment. It is known that physical exercise activates the endocannabinoid system and that stimulation of cannabinoid CB1 receptors (CB1Rs) promotes synaptic plasticity in both rodents and humans. We thus tested whether CB1R genetic variants affect responsiveness to exercise therapy. Methods: We evaluated the effect of a genetic variant of the CB1R associated with reduced receptor expression (patients with long AAT trinucleotide short tandem repeats in the CNR1 gene) on long-term potentiation (LTP)–like cortical plasticity induced by transcranial magnetic theta burst stimulation (TBS) of the motor cortex and, in parallel, on clinical response to exercise therapy in patients with multiple sclerosis. Results: We found that patients with long AAT CNR1 repeats do not express TBS-induced LTP-like cortical plasticity and show poor clinical benefit after exercise therapy. Conclusions: Our results provide the first evidence that genetic differences within the CB1R may influence clinical responses to exercise therapy, and they strengthen the hypothesis that CB1Rs are involved in the regulation of synaptic plasticity and in the control of spasticity in humans. This information might be of great relevance for patient stratification and personalized rehabilitation treatment programs. PMID:25520956

  9. Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1

    PubMed Central

    Bukhari, Noreen; Burman, Poromendro N.; Hussein, Ayan; Demars, Michael P.; Sadahiro, Masato; Brady, Daniel M.; Tsirka, Stella E.; Russo, Scott J.

    2015-01-01

    Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA-dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1-tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders. SIGNIFICANCE STATEMENT Experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain in correlation with the decline in cortical plasticity when mice are raised in standard cages. We demonstrated that removal of Lynx1, one of negative regulators of plasticity, unmasks experience-dependent tPA elevation in visual cortex of adult mice reared in standard cages. This proteolytic elevation facilitated dendritic spine reduction

  10. Abnormal cortical synaptic plasticity in minimal hepatic encephalopathy.

    PubMed

    Golaszewski, Stefan; Langthaler, Patrick B; Schwenker, Kerstin; Florea, Cristina; Christova, Monica; Brigo, Francesco; Trinka, Eugen; Nardone, Raffaele

    2016-07-01

    Minimal hepatic encephalopathy (MHE) represents the earliest stage of hepatic encephalopathy (HE). MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, while obvious clinical manifestations are lacking. In the present study, we aimed at assessing whether subjects with MHE showed alterations in synaptic plasticity within the motor cortex. Previous findings suggest that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. We employed therefore the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Fifteen patients with MHE and 15 age- and sex-matched cirrhotic patients without MHE were recruited. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min. In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude. On the contrary, in patients with MHE the MEP amplitude was slightly reduced after PAS. These findings demonstrated that associative sensorimotor plasticity, an indirect probe for motor learning, is impaired in MHE patients. PMID:27475415

  11. Cortical surface area and cortical thickness in the precuneus of adult humans.

    PubMed

    Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

    2015-02-12

    The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

  12. Role of adult neurogenesis in hippocampal-cortical memory consolidation.

    PubMed

    Kitamura, Takashi; Inokuchi, Kaoru

    2014-01-01

    Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

  13. Rapid eye movement sleep promotes cortical plasticity in the developing brain

    PubMed Central

    Dumoulin Bridi, Michelle C.; Aton, Sara J.; Seibt, Julie; Renouard, Leslie; Coleman, Tammi; Frank, Marcos G.

    2015-01-01

    Rapid eye movement sleep is maximal during early life, but its function in the developing brain is unknown. We investigated the role of rapid eye movement sleep in a canonical model of developmental plasticity in vivo (ocular dominance plasticity in the cat) induced by monocular deprivation. Preventing rapid eye movement sleep after monocular deprivation reduced ocular dominance plasticity and inhibited activation of a kinase critical for this plasticity (extracellular signal–regulated kinase). Chronic single-neuron recording in freely behaving cats further revealed that cortical activity during rapid eye movement sleep resembled activity present during monocular deprivation. This corresponded to times of maximal extracellular signal–regulated kinase activation. These findings indicate that rapid eye movement sleep promotes molecular and network adaptations that consolidate waking experience in the developing brain. PMID:26601213

  14. A role for maternal physiological state in preserving auditory cortical plasticity for salient infant calls

    PubMed Central

    Lin, Frank G.; Galindo-Leon, Edgar E.; Ivanova, Tamara N.; Mappus, Rudolph C.; Liu, Robert C.

    2013-01-01

    A growing interest in sensory system plasticity in the natural context of motherhood has created the need to investigate how intrinsic physiological state (e.g., hormonal, motivational, etc.) interacts with sensory experience to drive adaptive cortical plasticity for behaviorally relevant stimuli. Using a maternal mouse model of auditory cortical inhibitory plasticity for ultrasonic pup calls, we examined the role of pup care versus maternal physiological state in the long-term retention of this plasticity. Very recent experience caring for pups by Early Cocarers, which are virgins, produced stronger call-evoked lateral-band inhibition in auditory cortex. However, this plasticity was absent when measured post-weaning in Cocarers, even though it was present at the same time point in Mothers, whose pup experience occurred under a maternal physiological state. A two-alternative choice phonotaxis task revealed that the same animal groups (Early Cocarers and Mothers) demonstrating stronger lateral-band inhibition also preferred pup calls over a neutral sound, a correlation consistent with the hypothesis that this inhibitory mechanism may play a mnemonic role and is engaged to process sounds that are particularly salient. Our electrophysiological data hints at a possible mechanism through which the maternal physiological state may act to preserve the cortical plasticity: selectively suppressing detrimental spontaneous activity in neurons that are responsive to calls, an effect observed only in Mothers. Taken together, the maternal physiological state during the care of pups may help maintain the memory trace of behaviorally salient infant cues within core auditory cortex, potentially ensuring a more rapid induction of future maternal behavior. PMID:23707982

  15. Functional near-infrared spectroscopy maps cortical plasticity underlying altered motor performance induced by transcranial direct current stimulation

    PubMed Central

    Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann M.; Alexandrakis, George

    2013-01-01

    Abstract. Transcranial direct current stimulation (tDCS) of the human sensorimotor cortex during physical rehabilitation induces plasticity in the injured brain that improves motor performance. Bi-hemispheric tDCS is a noninvasive technique that modulates cortical activation by delivering weak current through a pair of anodal–cathodal (excitation–suppression) electrodes, placed on the scalp and centered over the primary motor cortex of each hemisphere. To quantify tDCS-induced plasticity during motor performance, sensorimotor cortical activity was mapped during an event-related, wrist flexion task by functional near-infrared spectroscopy (fNIRS) before, during, and after applying both possible bi-hemispheric tDCS montages in eight healthy adults. Additionally, torque applied to a lever device during isometric wrist flexion and surface electromyography measurements of major muscle group activity in both arms were acquired concurrently with fNIRS. This multiparameter approach found that hemispheric suppression contralateral to wrist flexion changed resting-state connectivity from intra-hemispheric to inter-hemispheric and increased flexion speed (p<0.05). Conversely, exciting this hemisphere increased opposing muscle output resulting in a decrease in speed but an increase in accuracy (p<0.05 for both). The findings of this work suggest that tDCS with fNIRS and concurrent multimotor measurements can provide insights into how neuroplasticity changes muscle output, which could find future use in guiding motor rehabilitation. PMID:24193947

  16. Induction of plasticity in the dominant and non-dominant motor cortices of humans.

    PubMed

    Ridding, M C; Flavel, S C

    2006-06-01

    There are clear hemispheric differences in the human motor system. Studies using magnetic resonance morphometry have shown that representation of hand muscles is larger in the dominant hemisphere than the non-dominant hemisphere. There is some limited evidence of electrophysiological differences between hemispheres. For example, it has been reported recently that there is less intracortical inhibition in the dominant hemisphere than the non-dominant hemisphere, and it has been hypothesised that this reduction in inhibition may facilitate use-dependent plasticity in the dominant motor cortex. In the present study we examined this hypothesis in human subjects by examining plasticity induction in both dominant and non-dominant hemispheres using an experimental paradigm known to induce motor cortical plasticity, namely paired associative stimulation (PAS). Additionally, we investigated changes in dominant and non-dominant hand performance on a simple ballistic training task. Short-interval intracortical inhibition (SICI) was also measured for both dominant and non-dominant hands at a range of conditioning intensities. There was significantly less SICI in the dominant motor cortical hand area than in the non-dominant hand area. PAS induced a significant, and similar, increase in motor cortical excitability in both the dominant and non-dominant hemispheres. Motor training resulted in significant performance improvement in both dominant and non-dominant hands. However, there was significantly more improvement in the non-dominant hand. The results from these studies provide some further evidence of electrophysiological differences between the motor cortices of the two hemispheres. Additionally, these findings offer no support for the hypothesis that the dominant hemisphere is positioned more favourably, due to decreased inhibitory tone, than the non-dominant hemisphere for use-dependent plasticity. PMID:16501966

  17. 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.

  18. Plasticity in the prefrontal cortex of adult rats

    PubMed Central

    Kolb, Bryan; Gibb, Robbin

    2015-01-01

    We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density) in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions. PMID:25691857

  19. Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players.

    PubMed

    Chieffo, Raffaella; Straffi, Laura; Inuggi, Alberto; Gonzalez-Rosa, Javier J; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

    2016-01-01

    Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere. PMID:27336584

  20. Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players.

    PubMed

    Chieffo, Raffaella; Straffi, Laura; Inuggi, Alberto; Gonzalez-Rosa, Javier J; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

    2016-01-01

    Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere.

  1. Motor Cortical Plasticity to Training Started in Childhood: The Example of Piano Players

    PubMed Central

    Inuggi, Alberto; Gonzalez-Rosa, Javier J.; Spagnolo, Francesca; Coppi, Elisabetta; Nuara, Arturo; Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

    2016-01-01

    Converging evidence suggest that motor training is associated with early and late changes of the cortical motor system. Transcranial magnetic stimulation (TMS) offers the possibility to study plastic rearrangements of the motor system in physiological and pathological conditions. We used TMS to characterize long-term changes in upper limb motor cortical representation and interhemispheric inhibition associated with bimanual skill training in pianists who started playing in an early age. Ipsilateral silent period (iSP) and cortical TMS mapping of hand muscles were obtained from 30 strictly right-handed subjects (16 pianists, 14 naïve controls), together with electromyographic recording of mirror movements (MMs) to voluntary hand movements. In controls, motor cortical representation of hand muscles was larger on the dominant (DH) than on the non-dominant hemisphere (NDH). On the contrary, pianists showed symmetric cortical output maps, being their DH less represented than in controls. In naïve subjects, the iSP was smaller on the right vs left abductor pollicis brevis (APB) indicating a weaker inhibition from the NDH to the DH. In pianists, interhemispheric inhibition was more symmetric as their DH was better inhibited than in controls. Electromyographic MMs were observed only in naïve subjects (7/14) and only to voluntary movement of the non-dominant hand. Subjects with MM had a lower iSP area on the right APB compared with all the others. Our findings suggest a more symmetrical motor cortex organization in pianists, both in terms of muscle cortical representation and interhemispheric inhibition. Although we cannot disentangle training-related from preexisting conditions, it is possible that long-term bimanual practice may reshape motor cortical representation and rebalance interhemispheric interactions, which in naïve right-handed subjects would both tend to favour the dominant hemisphere. PMID:27336584

  2. Cortical plasticity induced by short-term unimodal and multimodal musical training.

    PubMed

    Lappe, Claudia; Herholz, Sibylle C; Trainor, Laurel J; Pantev, Christo

    2008-09-24

    Learning to play a musical instrument requires complex multimodal skills involving simultaneous perception of several sensory modalities: auditory, visual, somatosensory, as well as the motor system. Therefore, musical training provides a good and adequate neuroscientific model to study multimodal brain plasticity effects in humans. Here, we investigated the impact of short-term unimodal and multimodal musical training on brain plasticity. Two groups of nonmusicians were musically trained over the course of 2 weeks. One group [sensorimotor-auditory (SA)] learned to play a musical sequence on the piano, whereas the other group [auditory (A)] listened to and made judgments about the music that had been played by participants of the sensorimotor-auditory group. Training-induced cortical plasticity was assessed by recording the musically elicited mismatch negativity (MMNm) from magnetoencephalographic measurements before and after training. SA and A groups showed significantly different cortical responses after training. Specifically, the SA group showed significant enlargement of MMNm after training compared with the A group, reflecting greater enhancement of musical representations in auditory cortex after sensorimotor-auditory training compared with after mere auditory training. Thus, we have experimentally demonstrated that not only are sensorimotor and auditory systems connected, but also that sensorimotor-auditory training causes plastic reorganizational changes in the auditory cortex over and above changes introduced by auditory training alone.

  3. Homeostatic plasticity mechanisms are required for juvenile, but not adult, ocular dominance plasticity

    PubMed Central

    Ranson, Adam; Cheetham, Claire E. J.; Fox, Kevin; Sengpiel, Frank

    2012-01-01

    Ocular dominance (OD) plasticity in the visual cortex is a classic model system for understanding developmental plasticity, but the visual cortex also shows plasticity in adulthood. Whether the plasticity mechanisms are similar or different at the two ages is not clear. Several plasticity mechanisms operate during development, including homeostatic plasticity, which acts to maintain the total excitatory drive to a neuron. In agreement with this idea, we found that an often-studied substrain of C57BL/6 mice, C57BL/6JOlaHsd (6JOla), lacks both the homeostatic component of OD plasticity as assessed by intrinsic signal imaging and synaptic scaling of mEPSC amplitudes after a short period of dark exposure during the critical period, whereas another substrain, C57BL/6J (6J), exhibits both plasticity processes. However, in adult mice, OD plasticity was identical in the 6JOla and 6J substrains, suggesting that adult plasticity occurs by a different mechanism. Consistent with this interpretation, adult OD plasticity was normal in TNFα knockout mice, which are known to lack juvenile synaptic scaling and the homeostatic component of OD plasticity, but was absent in adult α-calcium/calmodulin-dependent protein kinase II;T286A (αCaMKIIT286A) mice, which have a point mutation that prevents autophosphorylation of αCaMKII. We conclude that increased responsiveness to open-eye stimulation after monocular deprivation during the critical period is a homeostatic process that depends mechanistically on synaptic scaling during the critical period, whereas in adult mice it is mediated by a different mechanism that requires αCaMKII autophosphorylation. Thus, our study reveals a transition between homeostatic and long-term potentiation–like plasticity mechanisms with increasing age. PMID:22232689

  4. Experience-dependent plasticity of mature adult-born neurons.

    PubMed

    Livneh, Yoav; Mizrahi, Adi

    2012-01-01

    The adult olfactory bulb and hippocampus are continuously supplied with newborn neurons that are thought to possess a capacity for plasticity only at a young neuronal age, mainly during the early stages of integration into the network. We find that the two main types of adult-born neurons in the mouse olfactory bulb undergo experience-dependent plasticity long after maturation and integration, as evidenced by stabilization of synaptic turnover rates. Thus, the potential time window for plasticity of adult-born neurons extends well into maturity. PMID:22081159

  5. Distinct molecular components for thalamic- and cortical-dependent plasticity in the lateral amygdala

    PubMed Central

    Mirante, Osvaldo; Brandalise, Federico; Bohacek, Johannes; Mansuy, Isabelle M.

    2014-01-01

    N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala (LA) is a form of synaptic plasticity thought to be a cellular substrate for the extinction of fear memory. The LA receives converging inputs from the sensory thalamus and neocortex that are weakened following fear extinction. Combining field and patch-clamp electrophysiological recordings in mice, we show that paired-pulse low-frequency stimulation can induce a robust LTD at thalamic and cortical inputs to LA, and we identify different underlying molecular components at these pathways. We show that while LTD depends on NMDARs and activation of the protein phosphatases PP2B and PP1 at both pathways, it requires NR2B-containing NMDARs at the thalamic pathway, but NR2C/D-containing NMDARs at the cortical pathway. LTD appears to be induced post-synaptically at the thalamic input but presynaptically at the cortical input, since post-synaptic calcium chelation and NMDAR blockade prevent thalamic but not cortical LTD. These results highlight distinct molecular features of LTD in LA that may be relevant for traumatic memory and its erasure, and for pathologies such as post-traumatic stress disorder (PTSD). PMID:25071439

  6. 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.

  7. Adult Mouse Cortical Cell Taxonomy by Single Cell Transcriptomics

    PubMed Central

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T.; Sorensen, Staci A.; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M.; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-01-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. Here, we construct a cellular taxonomy of one cortical region, primary visual cortex, in adult mice based on single cell RNA-sequencing. We identify 49 transcriptomic cell types including 23 GABAergic, 19 glutamatergic and seven non-neuronal types. We also analyze cell-type specific mRNA processing and characterize genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we show that some of our transcriptomic cell types display specific and differential electrophysiological and axon projection properties, thereby confirming that the single cell transcriptomic signatures can be associated with specific cellular properties. PMID:26727548

  8. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics.

    PubMed

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T; Sorensen, Staci A; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-02-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell type-specific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties.

  9. The first successful lower extremity transplantation: 6-year follow-up and implications for cortical plasticity.

    PubMed

    Fattah, A; Cypel, T; Donner, E J; Wang, F; Alman, B A; Zuker, R M

    2011-12-01

    Vascularized composite allotransplantation as a viable reconstructive option is gaining recognition and new cases are being reported with increasing frequency including hand, face and laryngeal transplantation. However, only one successful complete lower limb transplantation has been reported to date, in which a functioning limb from one ischiopagus twin with a lethal cardiac anomaly was transplanted to the other. Six years later, the patient is mobilizing well and engaging in sporting activities with her peers in a mainstream school. Clinical evaluation of motor and sensory modalities demonstrated a good functional result. Quality of life was assessed using the short form-36 health survey and lower extremity functional scale disclosing a high level of social and physical capacity. Functional magnetic resonance imaging was performed and showed cortical integration of the limb; the implications of cortical plasticity and vascularized composite allotransplantation for the correction of congenital limb anomalies are presented. PMID:21991888

  10. Chondroitinase enhances cortical map plasticity and increases functionally active sprouting axons after brain injury.

    PubMed

    Harris, Neil G; Nogueira, Marcia S M; Verley, Derek R; Sutton, Richard L

    2013-07-15

    The beneficial effect of interventions with chondroitinase ABC enzyme to reduce axon growth-inhibitory chondroitin sulphate side chains after central nervous system injuries has been mainly attributed to enhanced axonal sprouting. After traumatic brain injury (TBI), it is unknown whether newly sprouting axons that occur as a result of interventional strategies are able to functionally contribute to existing circuitry, and it is uncertain whether maladaptive sprouting occurs to increase the well-known risk for seizure activity after TBI. Here, we show that after a controlled cortical impact injury in rats, chondroitinase infusion into injured cortex at 30 min and 3 days reduced c-Fos⁺ cell staining resulting from the injury alone at 1 week postinjury, indicating that at baseline, abnormal spontaneous activity is likely to be reduced, not increased, with this type of intervention. c-Fos⁺ cell staining elicited by neural activity from stimulation of the affected forelimb 1 week after injury was significantly enhanced by chondroitinase, indicating a widespread effect on cortical map plasticity. Underlying this map plasticity was a larger contribution of neuronal, rather than glial cells and an absence of c-Fos⁺ cells surrounded by perineuronal nets that were normally present in stimulated naïve rats. After injury, chondroitin sulfate proteoglycan digestion produced the expected increase in growth-associated protein 43-positive axons and perikarya, of which a significantly greater number were double labeled for c-Fos after intervention with chondroitinase, compared to vehicle. These data indicate that chondroitinase produces significant gains in cortical map plasticity after TBI, and that either axonal sprouting and/or changes in perineuronal nets may underlie this effect. Chondroitinase dampens, rather than increases nonspecific c-Fos activity after brain injury, and induction of axonal sprouting is not maladaptive because greater numbers are functionally

  11. Cortical and thalamic connectivity of the auditory anterior ectosylvian cortex of early-deaf cats: Implications for neural mechanisms of crossmodal plasticity.

    PubMed

    Meredith, M Alex; Clemo, H Ruth; Corley, Sarah B; Chabot, Nicole; Lomber, Stephen G

    2016-03-01

    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

  12. Emergence of cortical inhibition by coordinated sensory-driven plasticity at distinct synaptic loci.

    PubMed

    Chittajallu, Ramesh; Isaac, John T R

    2010-10-01

    Feedforward GABAergic inhibition sets the dendritic integration window, thereby controlling timing and output in cortical circuits. However, the manner in which feedforward inhibitory circuits emerge is unclear, despite this being a critical step for neocortical development and function. We found that sensory experience drove plasticity of the feedforward inhibitory circuit in mouse layer 4 somatosensory barrel cortex in the second postnatal week via two distinct mechanisms. First, sensory experience selectively strengthened thalamocortical-to-feedforward interneuron inputs via a presynaptic mechanism but did not regulate other inhibitory circuit components. Second, experience drove a postsynaptic mechanism in which a downregulation of a prominent thalamocortical NMDA excitatory postsynaptic potential in stellate cells regulated the final expression of functional feedforward inhibitory input. Thus, experience is required for specific, coordinated changes at thalamocortical synapses onto both inhibitory and excitatory neurons, producing a circuit plasticity that results in maturation of functional feedforward inhibition in layer 4. PMID:20871602

  13. Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram.

    PubMed

    Noh, Nor Azila

    2016-07-01

    Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/depression (LTP-/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses.

  14. Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram.

    PubMed

    Noh, Nor Azila

    2016-07-01

    Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/depression (LTP-/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses. PMID:27660540

  15. Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram

    PubMed Central

    Noh, Nor Azila

    2016-01-01

    Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/depression (LTP−/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses. PMID:27660540

  16. Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram

    PubMed Central

    Noh, Nor Azila

    2016-01-01

    Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/depression (LTP−/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses.

  17. Storing maternal memories: Hypothesizing an interaction of experience and estrogen on sensory cortical plasticity to learn infant cues

    PubMed Central

    Banerjee, Sunayana B.; Liu, Robert C.

    2013-01-01

    Much of the literature on maternal behavior has focused on the role of infant experience and hormones in a canonical subcortical circuit for maternal motivation and maternal memory. Although early studies demonstrated that the cerebral cortex also plays a significant role in maternal behaviors, little has been done to explore what that role may be. Recent work though has provided evidence that the cortex, particularly sensory cortices, contains correlates of sensory memories of infant cues, consistent with classical studies of experience-dependent sensory cortical plasticity in non-maternal paradigms. By reviewing the literature from both the maternal behavior and sensory cortical plasticity fields, focusing on the auditory modality, we hypothesize that maternal hormones (predominantly estrogen) may act to prime auditory cortical neurons for a longer-lasting neural trace of infant vocal cues, thereby facilitating recognition and discrimination. This could then more efficiently activate the subcortical circuit to elicit and sustain maternal behavior. PMID:23916405

  18. Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging.

    PubMed

    Lalo, Ulyana; Rasooli-Nejad, Seyed; Pankratov, Yuriy

    2014-10-01

    Maintaining brain function during aging is very important for mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals, and glial cells, which maintain the well-being and function of neurons. Still, the study of age-related changes in neuron-glia signalling is far from complete. We have shown previously that cortical astrocytes are capable of releasing ATP by a quantal soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complex-dependent mechanism. Release of ATP from cortical astrocytes can be activated via various pathways, including direct UV-uncaging of intracellular Ca²⁺ or G-protein-coupled receptors. Importantly, release of both ATP and glutamate from neocortical astrocytes was not observed in brain slices of dominant-negative SNARE (dnSNARE) mice, expressing dnSNARE domain selectively in astrocytes. We also discovered that astrocyte-driven ATP can cause significant attenuation of synaptic inhibition in the pyramidal neurons via Ca²⁺-interaction between the neuronal ATP and γ-aminobutyric acid (GABA) receptors. Furthermore, we showed that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Our recent data have shown that an age-related decrease in the astroglial Ca²⁺ signalling can cause a substantial decrease in the exocytosis of gliotransmitters, in particular ATP. Age-related impairment of ATP release from cortical astrocytes can cause a decrease in the extent of astroglial modulation of synaptic transmission in the neocortex and can therefore contribute to the age-related impairment of synaptic plasticity and cognitive decline. Combined, our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function. PMID:25233403

  19. Cortical and brainstem plasticity in Tourette syndrome and obsessive-compulsive disorder.

    PubMed

    Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Berardelli, Isabella; Roselli, Valentina; Pasquini, Massimo; Cardona, Francesco; Berardelli, Alfredo

    2014-10-01

    pathophysiology of Gilles de la Tourette syndrome. However, obsessive-compulsive disorder patients have normal cortical and brainstem plasticity.

  20. Caudal Ganglionic Eminence Precursor Transplants Disperse and Integrate as Lineage-Specific Interneurons but Do Not Induce Cortical Plasticity.

    PubMed

    Larimer, Phillip; Spatazza, Julien; Espinosa, Juan Sebastian; Tang, Yunshuo; Kaneko, Megumi; Hasenstaub, Andrea R; Stryker, Michael P; Alvarez-Buylla, Arturo

    2016-08-01

    The maturation of inhibitory GABAergic cortical circuits regulates experience-dependent plasticity. We recently showed that the heterochronic transplantation of parvalbumin (PV) or somatostatin (SST) interneurons from the medial ganglionic eminence (MGE) reactivates ocular dominance plasticity (ODP) in the postnatal mouse visual cortex. Might other types of interneurons similarly induce cortical plasticity? Here, we establish that caudal ganglionic eminence (CGE)-derived interneurons, when transplanted into the visual cortex of neonatal mice, migrate extensively in the host brain and acquire laminar distribution, marker expression, electrophysiological properties, and visual response properties like those of host CGE interneurons. Although transplants from the anatomical CGE do induce ODP, we found that this plasticity reactivation is mediated by a small fraction of MGE-derived cells contained in the transplant. These findings demonstrate that transplanted CGE cells can successfully engraft into the postnatal mouse brain and confirm the unique role of MGE lineage neurons in the induction of ODP. PMID:27425623

  1. Relationships among Cortical Thickness, Reading Skill, and Print Exposure in Adults

    ERIC Educational Resources Information Center

    Goldman, Jason G.; Manis, Frank R.

    2013-01-01

    This study investigated relationships among cortical thickness in the left-hemisphere reading network, and reading skill and experience in adult nonimpaired readers. Given the relationship between print exposure and reading, it is possible that print exposure is related to cortical structure. The pattern of correlations indicated that individuals…

  2. Structural plasticity of axon terminals in the adult.

    PubMed

    Gogolla, Nadine; Galimberti, Ivan; Caroni, Pico

    2007-10-01

    There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity complements that of postsynaptic spines, but axonal plasticity samples larger volumes of neuropil, and has a larger impact on circuit remodeling. Axons from distinct neurons exhibit unique ratios of stable (t1/2>9 months) and dynamic (t1/2 5-20 days) boutons, which persist as spatially intermingled subgroups along terminal arbors. In addition, phases of side-branch dynamics mediate larger scale remodeling guided by synaptogenesis. The plasticity is most pronounced during critical periods; its patterns and outcome are controlled by Hebbian mechanisms and intrinsic neuronal factors. Novel experience, skill learning, life-style, and age can persistently modify local circuit structure through axonal structural plasticity.

  3. Chronic fluoxetine treatment alters the structure, connectivity and plasticity of cortical interneurons.

    PubMed

    Guirado, Ramon; Perez-Rando, Marta; Sanchez-Matarredona, David; Castrén, Eero; Nacher, Juan

    2014-10-01

    Novel hypotheses suggest that antidepressants, such as the selective serotonin reuptake inhibitor fluoxetine, induce neuronal structural plasticity, resembling that of the juvenile brain, although the underlying mechanisms of this reopening of the critical periods still remain unclear. However, recent studies suggest that inhibitory networks play an important role in this structural plasticity induced by fluoxetine. For this reason we have analysed the effects of a chronic fluoxetine treatment in the hippocampus and medial prefrontal cortex (mPFC) of transgenic mice displaying eGFP labelled interneurons. We have found an increase in the expression of molecules related to critical period plasticity, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), GAD67/65 and synaptophysin, as well as a reduction in the number of parvalbumin expressing interneurons surrounded by perineuronal nets. We have also described a trend towards decrease in the perisomatic inhibitory puncta on pyramidal neurons in the mPFC and an increase in the density of inhibitory puncta on eGFP interneurons. Finally, we have found that chronic fluoxetine treatment affects the structure of interneurons in the mPFC, increasing their dendritic spine density. The present study provides evidence indicating that fluoxetine promotes structural changes in the inhibitory neurons of the adult cerebral cortex, probably through alterations in plasticity-related molecules of neurons or the extracellular matrix surrounding them, which are present in interneurons and are known to be crucial for the development of the critical periods of plasticity in the juvenile brain.

  4. Cortical Plasticity Induced by Spike-Triggered Microstimulation in Primate Somatosensory Cortex

    PubMed Central

    Song, Weiguo; Kerr, Cliff C.; Lytton, William W.; Francis, Joseph T.

    2013-01-01

    Electrical stimulation of the nervous system for therapeutic purposes, such as deep brain stimulation in the treatment of Parkinson’s disease, has been used for decades. Recently, increased attention has focused on using microstimulation to restore functions as diverse as somatosensation and memory. However, how microstimulation changes the neural substrate is still not fully understood. Microstimulation may cause cortical changes that could either compete with or complement natural neural processes, and could result in neuroplastic changes rendering the region dysfunctional or even epileptic. As part of our efforts to produce neuroprosthetic devices and to further study the effects of microstimulation on the cortex, we stimulated and recorded from microelectrode arrays in the hand area of the primary somatosensory cortex (area 1) in two awake macaque monkeys. We applied a simple neuroprosthetic microstimulation protocol to a pair of electrodes in the area 1 array, using either random pulses or pulses time-locked to the recorded spiking activity of a reference neuron. This setup was replicated using a computer model of the thalamocortical system, which consisted of 1980 spiking neurons distributed among six cortical layers and two thalamic nuclei. Experimentally, we found that spike-triggered microstimulation induced cortical plasticity, as shown by increased unit-pair mutual information, while random microstimulation did not. In addition, there was an increased response to touch following spike-triggered microstimulation, along with decreased neural variability. The computer model successfully reproduced both qualitative and quantitative aspects of the experimental findings. The physiological findings of this study suggest that even simple microstimulation protocols can be used to increase somatosensory information flow. PMID:23472086

  5. Paired associative transspinal and transcortical stimulation produces plasticity in human cortical and spinal neuronal circuits.

    PubMed

    Dixon, Luke; Ibrahim, Mohamed M; Santora, Danielle; Knikou, Maria

    2016-08-01

    Anatomical, physiological, and functional connectivity exists between the neurons of the primary motor cortex (M1) and spinal cord. Paired associative stimulation (PAS) produces enduring changes in M1, based on the Hebbian principle of associative plasticity. The present study aimed to establish neurophysiological changes in human cortical and spinal neuronal circuits by pairing noninvasive transspinal stimulation with transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40 min at precise interstimulus intervals, with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor threshold, and reduced the soleus Hoffmann's reflex (H-reflex) low frequency-mediated homosynaptic depression. Transcortical-transspinal PAS did not affect intracortical circuits, decreased M1 excitability, and reduced the soleus H-reflex-paired stimulation pulses' mediated postactivation depression. Both protocols affected the excitation threshold of group Ia afferents and motor axons. These findings clearly indicate that the pairing of transspinal with transcortical stimulation produces cortical and spinal excitability changes based on the timing interval and functional network interactions between the two associated inputs. This new PAS paradigm may constitute a significant neuromodulation method with physiological impact, because it can be used to alter concomitantly excitability of intracortical circuits, corticospinal neurons, and spinal inhibition in humans. PMID:27281748

  6. Development and Maturation of Embryonic Cortical Neurons Grafted into the Damaged Adult Motor Cortex

    PubMed Central

    Ballout, Nissrine; Frappé, Isabelle; Péron, Sophie; Jaber, Mohamed; Zibara, Kazem; Gaillard, Afsaneh

    2016-01-01

    Injury to the human central nervous system can lead to devastating consequences due to its poor ability to self-repair. Neural transplantation aimed at replacing lost neurons and restore functional circuitry has proven to be a promising therapeutical avenue. We previously reported in adult rodent animal models with cortical lesions that grafted fetal cortical neurons could effectively re-establish specific patterns of projections and synapses. The current study was designed to provide a detailed characterization of the spatio-temporal in vivo development of fetal cortical transplanted cells within the lesioned adult motor cortex and their corresponding axonal projections. We show here that as early as 2 weeks after grafting, cortical neuroblasts transplanted into damaged adult motor cortex developed appropriate projections to cortical and subcortical targets. Grafted cells initially exhibited characteristics of immature neurons, which then differentiated into mature neurons with appropriate cortical phenotypes where most were glutamatergic and few were GABAergic. All cortical subtypes identified with the specific markers CTIP2, Cux1, FOXP2, and Tbr1 were generated after grafting as evidenced with BrdU co-labeling. The set of data provided here is of interest as it sets biological standards for future studies aimed at replacing fetal cells with embryonic stem cells as a source of cortical neurons. PMID:27536221

  7. Cerebellar cortical degeneration in adult American Staffordshire Terriers.

    PubMed

    Olby, Natasha; Blot, Stephane; Thibaud, Jean-Laurent; Phillips, Jeff; O'Brien, Dennis P; Burr, Jeanne; Berg, Jason; Brown, Talmage; Breen, Matthew

    2004-01-01

    Adult-onset cerebellar cortical degeneration recently has been reported in American Staffordshire Terriers. We describe the clinical and histopathologic features of this disease and examine its mode of inheritance in 63 affected dogs. The age at which neurologic deficits 1st were recognized varied from 18 months to 9 years, with the majority of dogs presented to veterinarians between 4 and 6 years of age. Time from onset of clinical signs to euthanasia varied from 6 months to 6.5 years, with the majority of affected dogs surviving from 2 to 4 years. Initial neurologic findings included stumbling, truncal sway, and ataxia exacerbated by lifting the head up and negotiating stairs. Signs progressed to obvious ataxia characterized by dysmetria, nystagmus, coarse intention tremor, variable loss of menace reaction, marked truncal sway, and falling with transient opisthotonus. With continued progression, dogs became unable to walk without falling repeatedly. Cerebellar atrophy was visible on magnetic resonance images and on gross pathology. Histopathologic findings included marked loss of Purkinje neurons with thinning of the molecular and granular layers and increased cellularity of the cerebellar nuclei. The closest common ancestor of the dogs was born in the 1950s and inheritance was most consistent with an autosomal recessive mode of transmission with a prevalence estimated at 1 in 400 dogs. This inherited disease is comparable to the group of diseases known as spinocerebellar ataxias in humans. Many spinocerebellar ataxias in humans are caused by nucleotide repeats, and this genetic aberration merits investigation as a potential cause of the disease in American Staffordshire Terriers. PMID:15058771

  8. Regenerative capacity of adult cortical thymic epithelial cells.

    PubMed

    Rode, Immanuel; Boehm, Thomas

    2012-02-28

    Involution of the thymus is accompanied by a decline in the number of thymic epithelial cells (TECs) and a severely restricted peripheral repertoire of T-cell specificities. TECs are essential for T-cell differentiation; they originate from a bipotent progenitor that gives rise to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors. Upon acute selective near-total ablation during embryogenesis, regeneration of TECs fails, suggesting that losses from the pool of TEC progenitors are not compensated. However, it is unclear whether this is also true for the compartment-specific progenitors. The decline of cTECs is a prominent feature of thymic involution. Because cTECs support early stages of T-cell development and hence determine the overall lymphopoietic capacity of the thymus, it is possible that the lack of sustained regenerative capacity of cTEC progenitor cells underlies the process of thymic involution. Here, we examine this hypothesis by cell-type-specific conditional ablation of cTECs. Expression of the human diphtheria toxin receptor (hDTR) gene under the regulatory influence of the chemokine receptor Ccx-ckr1 gene renders cTECs sensitive to the cytotoxic effects of diphtheria toxin (DT). As expected, DT treatment of preadolescent and adult mice led to a dramatic loss of cTECs, accompanied by a rapid demise of immature thymocytes. Unexpectedly, however, the cTEC compartment regenerated after cessation of treatment, accompanied by the restoration of T-cell development. These findings provide the basis for the development of targeted interventions unlocking the latent regenerative potential of cTECs to counter thymic involution.

  9. Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring

    PubMed Central

    Miner, Daniel; Triesch, Jochen

    2016-01-01

    Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non-random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring. PMID:26866369

  10. The plasticity of the mirror system: How reward learning modulates cortical motor simulation of others

    PubMed Central

    Trilla Gros, Irene; Panasiti, Maria Serena; Chakrabarti, Bhismadev

    2015-01-01

    Cortical motor simulation supports the understanding of others' actions and intentions. This mechanism is thought to rely on the mirror neuron system (MNS), a brain network that is active both during action execution and observation. Indirect evidence suggests that (alpha/beta) mu suppression, an electroencephalographic (EEG) index of MNS activity, is modulated by reward. In this study we aimed to test the plasticity of the MNS by directly investigating the link between (alpha/beta) mu suppression and reward. 40 individuals from a general population sample took part in an evaluative conditioning experiment, where different neutral faces were associated with high or low reward values. In the test phase, EEG was recorded while participants viewed videoclips of happy expressions made by the conditioned faces. Alpha/beta mu suppression (identified using event-related desynchronisation of specific independent components) in response to rewarding faces was found to be greater than for non-rewarding faces. This result provides a mechanistic insight into the plasticity of the MNS and, more generally, into the role of reward in modulating physiological responses linked to empathy. PMID:25744871

  11. Methylphenidate and the juvenile brain: enhancement of attention at the expense of cortical plasticity?

    PubMed

    Urban, Kimberly R; Gao, Wen-Jun

    2013-12-01

    Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded as a relatively safe medication for the past several decades. However, a thorough review of the literature reveals that the age-dependent activities of the drug, as well as potential developmental effects, are largely ignored. In addition, the diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and excessive prescription of the drug. Recent studies have suggested that early life exposure of healthy rodent models to methylphenidate resulted in altered sleep/wake cycle, heightened stress reactivity, and, in fact, a dosage previously thought of as therapeutic depressed neuronal function in juvenile rats. Furthermore, juvenile rats exposed to low-dose methylphenidate displayed alterations in neural markers of plasticity, indicating that the drug might alter the basic properties of prefrontal cortical circuits. In this review of the current literature, we propose that juvenile exposure to methylphenidate may cause abnormal prefrontal function and impaired plasticity in the healthy brain, strengthening the case for developing a more thorough understanding of methylphenidate's actions on the developing, juvenile brain, as well as better diagnostic measures for ADHD.

  12. Cortical plasticity induced by short-term multimodal musical rhythm training.

    PubMed

    Lappe, Claudia; Trainor, Laurel J; Herholz, Sibylle C; Pantev, Christo

    2011-01-01

    Performing music is a multimodal experience involving the visual, auditory, and somatosensory modalities as well as the motor system. Therefore, musical training is an excellent model to study multimodal brain plasticity. Indeed, we have previously shown that short-term piano practice increase the magnetoencephalographic (MEG) response to melodic material in novice players. Here we investigate the impact of piano training using a rhythmic-focused exercise on responses to rhythmic musical material. Musical training with non musicians was conducted over a period of two weeks. One group (sensorimotor-auditory, SA) learned to play a piano sequence with a distinct musical rhythm, another group (auditory, A) listened to, and evaluated the rhythmic accuracy of the performances of the SA-group. Training-induced cortical plasticity was evaluated using MEG, comparing the mismatch negativity (MMN) in response to occasional rhythmic deviants in a repeating rhythm pattern before and after training. The SA-group showed a significantly greater enlargement of MMN and P2 to deviants after training compared to the A- group. The training-induced increase of the rhythm MMN was bilaterally expressed in contrast to our previous finding where the MMN for deviants in the pitch domain showed a larger right than left increase. The results indicate that when auditory experience is strictly controlled during training, involvement of the sensorimotor system and perhaps increased attentional recources that are needed in producing rhythms lead to more robust plastic changes in the auditory cortex compared to when rhythms are simply attended to in the auditory domain in the absence of motor production.

  13. Cortical oscillatory activity and the induction of plasticity in the human motor cortex.

    PubMed

    McAllister, Suzanne M; Rothwell, John C; Ridding, Michael C

    2011-05-01

    Repetitive transcranial magnetic stimulation paradigms such as continuous theta burst stimulation (cTBS) induce long-term potentiation- and long-term depression-like plasticity in the human motor cortex. However, responses to cTBS are highly variable and may depend on the activity of the cortex at the time of stimulation. We investigated whether power in different electroencephalogram (EEG) frequency bands predicted the response to subsequent cTBS, and conversely whether cTBS had after-effects on the EEG. cTBS may utilize similar mechanisms of plasticity to motor learning; thus, we conducted a parallel set of experiments to test whether ongoing electroencephalography could predict performance of a visuomotor training task, and whether training itself had effects on the EEG. Motor evoked potentials (MEPs) provided an index of cortical excitability pre- and post-intervention. The EEG was recorded over the motor cortex pre- and post-intervention, and power spectra were computed. cTBS reduced MEP amplitudes; however, baseline power in the delta, theta, alpha or beta frequencies did not predict responses to cTBS or learning of the visuomotor training task. cTBS had no effect on delta, theta, alpha or beta power. In contrast, there was an increase in alpha power following visuomotor training that was positively correlated with changes in MEP amplitude post-training. The results suggest that the EEG is not a useful state-marker for predicting responses to plasticity-inducing paradigms. The correlation between alpha power and changes in corticospinal excitability following visuomotor training requires further investigation, but may be related to disengagement of the somatosensory system important for motor memory consolidation. PMID:21488985

  14. Chronic fluoxetine treatment alters the structure, connectivity and plasticity of cortical interneurons.

    PubMed

    Guirado, Ramon; Perez-Rando, Marta; Sanchez-Matarredona, David; Castrén, Eero; Nacher, Juan

    2014-10-01

    Novel hypotheses suggest that antidepressants, such as the selective serotonin reuptake inhibitor fluoxetine, induce neuronal structural plasticity, resembling that of the juvenile brain, although the underlying mechanisms of this reopening of the critical periods still remain unclear. However, recent studies suggest that inhibitory networks play an important role in this structural plasticity induced by fluoxetine. For this reason we have analysed the effects of a chronic fluoxetine treatment in the hippocampus and medial prefrontal cortex (mPFC) of transgenic mice displaying eGFP labelled interneurons. We have found an increase in the expression of molecules related to critical period plasticity, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), GAD67/65 and synaptophysin, as well as a reduction in the number of parvalbumin expressing interneurons surrounded by perineuronal nets. We have also described a trend towards decrease in the perisomatic inhibitory puncta on pyramidal neurons in the mPFC and an increase in the density of inhibitory puncta on eGFP interneurons. Finally, we have found that chronic fluoxetine treatment affects the structure of interneurons in the mPFC, increasing their dendritic spine density. The present study provides evidence indicating that fluoxetine promotes structural changes in the inhibitory neurons of the adult cerebral cortex, probably through alterations in plasticity-related molecules of neurons or the extracellular matrix surrounding them, which are present in interneurons and are known to be crucial for the development of the critical periods of plasticity in the juvenile brain. PMID:24786752

  15. Playing and listening to tailor-made notched music: cortical plasticity induced by unimodal and multimodal training in tinnitus patients.

    PubMed

    Pape, Janna; Paraskevopoulos, Evangelos; Bruchmann, Maximilian; Wollbrink, Andreas; Rudack, Claudia; Pantev, Christo

    2014-01-01

    BACKGROUND. The generation and maintenance of tinnitus are assumed to be based on maladaptive functional cortical reorganization. Listening to modified music, which contains no energy in the range of the individual tinnitus frequency, can inhibit the corresponding neuronal activity in the auditory cortex. Music making has been shown to be a powerful stimulator for brain plasticity, inducing changes in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral measurements we evaluated the cortical plasticity effects of two months of (a) active listening to (unisensory) versus (b) learning to play (multisensory) tailor-made notched music in nonmusician tinnitus patients. Taking into account the fact that uni- and multisensory trainings induce different patterns of cortical plasticity we hypothesized that these two protocols will have different affects. RESULTS. Only the active listening (unisensory) group showed significant reduction of tinnitus related activity of the middle temporal cortex and an increase in the activity of a tinnitus-coping related posterior parietal area. CONCLUSIONS. These findings indicate that active listening to tailor-made notched music induces greater neuroplastic changes in the maladaptively reorganized cortical network of tinnitus patients while additional integration of other sensory modalities during training reduces these neuroplastic effects.

  16. Playing and Listening to Tailor-Made Notched Music: Cortical Plasticity Induced by Unimodal and Multimodal Training in Tinnitus Patients

    PubMed Central

    Rudack, Claudia

    2014-01-01

    Background. The generation and maintenance of tinnitus are assumed to be based on maladaptive functional cortical reorganization. Listening to modified music, which contains no energy in the range of the individual tinnitus frequency, can inhibit the corresponding neuronal activity in the auditory cortex. Music making has been shown to be a powerful stimulator for brain plasticity, inducing changes in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral measurements we evaluated the cortical plasticity effects of two months of (a) active listening to (unisensory) versus (b) learning to play (multisensory) tailor-made notched music in nonmusician tinnitus patients. Taking into account the fact that uni- and multisensory trainings induce different patterns of cortical plasticity we hypothesized that these two protocols will have different affects. Results. Only the active listening (unisensory) group showed significant reduction of tinnitus related activity of the middle temporal cortex and an increase in the activity of a tinnitus-coping related posterior parietal area. Conclusions. These findings indicate that active listening to tailor-made notched music induces greater neuroplastic changes in the maladaptively reorganized cortical network of tinnitus patients while additional integration of other sensory modalities during training reduces these neuroplastic effects. PMID:24895541

  17. Supratentorial ependymoma presenting as a cortical cyst with a mural nodule in an adult

    PubMed Central

    Tailor, Jignesh; Jaunmuktane, Zane; Brandner, Sebastian; Sethi, Huma

    2015-01-01

    Supratentorial ependymoma is a rare tumour in the adult central nervous system. We present an unusual case of supratentorial ependymoma in a young adult that presented as a pure cortical cyst with a mural nodule and discuss the differential diagnosis of such lesions in the brain. PMID:25589537

  18. Functional plasticity in the interposito-thalamo-cortical pathway during conditioning. Role of the interstimulus interval.

    PubMed

    Pananceau, M; Rispal-Padel, L

    2000-06-01

    In classic conditioning, the interstimulus interval (ISI) between the conditioned (CS) and unconditioned (US) stimulus is a critical parameter. The aim of the present experiment was to assess whether, during conditioning, modification of the CS-US interval could reliably produce changes in the functional properties of the interposito-thalamo-cortical pathways (INTCps). Five cats were prepared for chronic stimulation and recording from several brain regions along this pathway in awake animals. The CS was a weak electric shock applied on the interposed nucleus of the cerebellum in sites that initially elicited forelimb flexion (i.e., alpha motor responses) in three cats, and equal proportions of flexor and extensor responses in two cats. The US was an electric shock applied on the skin that elicited forelimb flexions. The motor and neurobiological effects of synchronous CS-US were compared with pairings in which the CS was applied 100 ms before US. Simultaneous and sequential application of CS and US produced different behavioral outcomes and resulted in different neural processes in the interposito-thalamo-cortical pathways (INTCps). The simultaneous presentation of stimuli only produced a small increase in excitability spreading to all the body representational zones of the primary motor cortex and a weak increase in the amplitude of the alpha motor response. In contrast, the sequential application led to a profound modification of the interposed output to neurons in the forelimb representation of the motor cortex. These robust neuronal correlates of conditioning were accompanied by a large facilitation of the alpha motor response (alpha-MR). There were also changes in the direction of misdirected alpha responses and an emergence of functionally appropriate, long-latency withdrawal forelimb flexion. These data revealed that, during conditioning, plastic changes within the thalamocortical connections are selectively induced by sequential information from central and

  19. Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice

    PubMed Central

    Ardiles, Alvaro O.; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M.; Palacios, Adrian G.; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C.; Martínez, Agustín D.

    2014-01-01

    The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory. PMID:25360084

  20. Adaptations of young adult rat cortical bone to 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

    1992-01-01

    To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

  1. Cortical stimulation consolidates and reactivates visual experience: neural plasticity from magnetic entrainment of visual activity.

    PubMed

    Liao, Hsin-I; Wu, Daw-An; Halelamien, Neil; Shimojo, Shinsuke

    2013-01-01

    Delivering transcranial magnetic stimulation (TMS) shortly after the end of a visual stimulus can cause a TMS-induced 'replay' or 'visual echo' of the visual percept. In the current study, we find an entrainment effect that after repeated elicitations of TMS-induced replay with the same visual stimulus, the replay can be induced by TMS alone, without the need for the physical visual stimulus. In Experiment 1, we used a subjective rating task to examine the phenomenal aspects of TMS-entrained replays. In Experiment 2, we used an objective masking paradigm to quantitatively validate the phenomenon and to examine the involvement of low-level mechanisms. Results showed that the TMS-entrained replay was not only phenomenally experienced (Exp.1), but also able to hamper letter identification (Exp.2). The findings have implications in several directions: (1) the visual cortical representation and iconic memory, (2) experience-based plasticity in the visual cortex, and (3) their relationship to visual awareness. PMID:23863977

  2. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation.

    PubMed

    Bieszczad, Kasia M; Bechay, Kiro; Rusche, James R; Jacques, Vincent; Kudugunti, Shashi; Miao, Wenyan; Weinberger, Norman M; McGaugh, James L; Wood, Marcelo A

    2015-09-23

    Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. Significance statement: Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by

  3. Condylar subchondral formation of cortical bone in adolescents and young adults.

    PubMed

    Lei, Jie; Liu, Mu-Qing; Yap, Adrian U Jin; Fu, Kai-Yuan

    2013-01-01

    We investigated subchondral formation of cortical bone in the condyles of adolescents and young adults, and looked for age-related and sex-related differences in bony formation with the aid of cone-beam computed tomography data in 1438 subjects aged between 10 and 30 years. The scans were part of the hospital's clinical protocol for patients seeking orthodontic or orthognathic treatment. No patient had signs or symptoms of temporomandibular disorders. Central images of the coronal and sagittal planes of the condyle were acquired and scored. Subchondral formation of cortical bone was seen as a high-density compact linear image, and subjects were classified into complete, partial, and no formation. Subchondral formation of cortical bone was first seen at the ages of 13-14 in boys and 12-13 in girls. Complete cortical bony formation was seen after the age of 22 years for men and 21 for women. We conclude that cortical bone begins to form around the periphery of the condyles during adolescence (12-14 years). A continuous, homogeneous, and compact cortical bony layer is established in young adults by the age of 21-22, indicating full development of the mandibular condyle. The condylar bone developed gradually and was generally fully developed a year earlier in women than men.

  4. Self-Organized Near-Zero-Lag Synchronization Induced by Spike-Timing Dependent Plasticity in Cortical Populations

    PubMed Central

    Matias, Fernanda S.; Carelli, Pedro V.; Mirasso, Claudio R.; Copelli, Mauro

    2015-01-01

    Several cognitive tasks related to learning and memory exhibit synchronization of macroscopic cortical areas together with synaptic plasticity at neuronal level. Therefore, there is a growing effort among computational neuroscientists to understand the underlying mechanisms relating synchrony and plasticity in the brain. Here we numerically study the interplay between spike-timing dependent plasticity (STDP) and anticipated synchronization (AS). AS emerges when a dominant flux of information from one area to another is accompanied by a negative time lag (or phase). This means that the receiver region pulses before the sender does. In this paper we study the interplay between different synchronization regimes and STDP at the level of three-neuron microcircuits as well as cortical populations. We show that STDP can promote auto-organized zero-lag synchronization in unidirectionally coupled neuronal populations. We also find synchronization regimes with negative phase difference (AS) that are stable against plasticity. Finally, we show that the interplay between negative phase difference and STDP provides limited synaptic weight distribution without the need of imposing artificial boundaries. PMID:26474165

  5. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  6. From perceptual to lexico-semantic analysis--cortical plasticity enabling new levels of processing.

    PubMed

    Schlaffke, Lara; Rüther, Naima N; Heba, Stefanie; Haag, Lauren M; Schultz, Thomas; Rosengarth, Katharina; Tegenthoff, Martin; Bellebaum, Christian; Schmidt-Wilcke, Tobias

    2015-11-01

    Certain kinds of stimuli can be processed on multiple levels. While the neural correlates of different levels of processing (LOPs) have been investigated to some extent, most of the studies involve skills and/or knowledge already present when performing the task. In this study we specifically sought to identify neural correlates of an evolving skill that allows the transition from perceptual to a lexico-semantic stimulus analysis. Eighteen participants were trained to decode 12 letters of Morse code that were presented acoustically inside and outside of the scanner environment. Morse code was presented in trains of three letters while brain activity was assessed with fMRI. Participants either attended to the stimulus length (perceptual analysis), or evaluated its meaning distinguishing words from nonwords (lexico-semantic analysis). Perceptual and lexico-semantic analyses shared a mutual network comprising the left premotor cortex, the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual analysis was associated with a strong brain activation in the SMA and the superior temporal gyrus bilaterally (STG), which remained unaltered from pre and post training. In the lexico-semantic analysis post learning, study participants showed additional activation in the left inferior frontal cortex (IFC) and in the left occipitotemporal cortex (OTC), regions known to be critically involved in lexical processing. Our data provide evidence for cortical plasticity evolving with a learning process enabling the transition from perceptual to lexico-semantic stimulus analysis. Importantly, the activation pattern remains task-related LOP and is thus the result of a decision process as to which LOP to engage in.

  7. From perceptual to lexico‐semantic analysis—cortical plasticity enabling new levels of processing

    PubMed Central

    Schlaffke, Lara; Rüther, Naima N.; Heba, Stefanie; Haag, Lauren M.; Schultz, Thomas; Rosengarth, Katharina; Tegenthoff, Martin; Bellebaum, Christian

    2015-01-01

    Abstract Certain kinds of stimuli can be processed on multiple levels. While the neural correlates of different levels of processing (LOPs) have been investigated to some extent, most of the studies involve skills and/or knowledge already present when performing the task. In this study we specifically sought to identify neural correlates of an evolving skill that allows the transition from perceptual to a lexico‐semantic stimulus analysis. Eighteen participants were trained to decode 12 letters of Morse code that were presented acoustically inside and outside of the scanner environment. Morse code was presented in trains of three letters while brain activity was assessed with fMRI. Participants either attended to the stimulus length (perceptual analysis), or evaluated its meaning distinguishing words from nonwords (lexico‐semantic analysis). Perceptual and lexico‐semantic analyses shared a mutual network comprising the left premotor cortex, the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual analysis was associated with a strong brain activation in the SMA and the superior temporal gyrus bilaterally (STG), which remained unaltered from pre and post training. In the lexico‐semantic analysis post learning, study participants showed additional activation in the left inferior frontal cortex (IFC) and in the left occipitotemporal cortex (OTC), regions known to be critically involved in lexical processing. Our data provide evidence for cortical plasticity evolving with a learning process enabling the transition from perceptual to lexico‐semantic stimulus analysis. Importantly, the activation pattern remains task‐related LOP and is thus the result of a decision process as to which LOP to engage in. Hum Brain Mapp 36:4512–4528, 2015. © 2015 The Authors. Human Brain Mapping Published byWiley Periodicals, Inc. PMID:26304153

  8. Magnetoencephalographic Analysis of Cortical Activity in Adults with and without Down Syndrome

    ERIC Educational Resources Information Center

    Virji-Babul, N.; Cheung, T.; Weeks, D.; Herdman, A. T.; Cheyne, D.

    2007-01-01

    Background: This preliminary study served as a pilot for an ongoing analysis of spectral power in adults with Down syndrome (DS) using a 151 channel whole head magnetoencephalography (MEG). The present study is the first step for examining and comparing cortical responses during spontaneous and task related activity in DS. Method: Cortical…

  9. Neuromagnetic imaging of movement-related cortical oscillations in children and adults: age predicts post-movement beta rebound.

    PubMed

    Gaetz, W; Macdonald, M; Cheyne, D; Snead, O C

    2010-06-01

    We measured visually-cued motor responses in two developmentally separate groups of children and compared these responses to a group of adults. We hypothesized that if post-movement beta rebound (PMBR) depends on developmentally sensitive processes, PMBR will be greatest in adults and progressively decrease in children performing a basic motor task as a function of age. Twenty children (10 young children 4-6 years; 10 adolescent children 11-13 years) and 10 adults all had MEG recorded during separate recordings of right and left index finger movements. Beta band (15-30 Hz) event-related desynchronization (ERD) of bi-lateral sensorimotor areas was observed to increase significantly from both contralateral and ipsilateral MI with age. Movement-related gamma synchrony (60-90 Hz) was also observed from contralateral MI for each age group. However, PMBR was significantly reduced in the 4-6 year group and, while more prominent, remained significantly diminished in the adolescent (11-13 year) age group as compared to adults. PMBR measures were weak or absent in the youngest children tested and appear maximally from bilateral MI in adults. Thus PMBR may reflect an age-dependent inhibitory process of the primary motor cortex which comes on-line with normal development. Previous studies have shown PMBR may be observed from MI following a variety of movement-related tasks in adult participants - however, the origin and purpose of the PMBR is unclear. The current study shows that the expected PMBR from MI observed from adults is increasingly diminished in adolescent and young children respectively. A reduction in PMBR from children may reflect reduced motor cortical inhibition. Relatively less motor inhibition may facilitate neuronal plasticity and promote motor learning in children. PMID:20116434

  10. Ultrastructural characteristics of human adult and infant cerebral cortical neurons.

    PubMed Central

    Ong, W Y; Garey, L J

    1991-01-01

    Biopsy specimens of human cerebral cortex from three adults and two infants were studied by correlating their light microscopic features in semithin sections with their ultrastructural characteristics. There was good tissue preservation, due to a minimum delay between obtaining the specimens and fixation. Pyramidal cells had a prominent apical dendrite, fine heterochromatin clumps in the nucleus and generally small numbers of cytoplasmic organelles, except for numerous free ribosomes in some of the large pyramids of Layers III to VI. Non-pyramidal cells lacked an apical dendrite and were further classified, on size and ultrastructure, into small, medium and large types. Large numbers of asymmetrical and symmetrical synapses were present in the neuropil but very few axosomatic synapses were found in the human cerebral cortex compared with subhuman primates and other mammals. Some symmetrical synapses were characterised by the presence of wide pre- and postsynaptic densities. The same general features of the adult cortex were also encountered in the infant, with certain exceptions. Many of the infant neurons had less densely packed heterochromatin, but greater numbers of free ribosomes, compared with the adult, and lipofuscin was absent. There was a total absence of myelinated fibres from the infant cortex; more large diameter dendrites were present than in the adult and axosomatic synapses were commoner. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:2050578

  11. Cortical responses from adults and infants to complex visual stimuli.

    PubMed

    Schulman-Galambos, C; Galambos, R

    1978-10-01

    Event-related potentials (ERPs) time-locked to the onset of visual stimuli were extracted from the EEG of normal adult (N = 16) and infant (N = 23) subjects. Subjects were not required to make any response. Stimuli delivered to the adults were 150 msec exposures of 2 sets of colored slides projected in 4 blocks, 2 in focus and 2 out of focus. Infants received 2-sec exposures of slides showing people, colored drawings or scenes from Disneyland, as well as 2-sec illuminations of the experimenter as she played a game or of a TV screen the baby was watching. The adult ERPs showed 6 waves (N1 through P4) in the 140--600-msec range; this included a positive wave at around 350 msec that was large when the stimuli were focused and smaller when they were not. The waves in the 150--200-msec range, by contrast, steadily dropped in amplitude as the experiment progressed. The infant ERPs differed greatly from the adult ones in morphology, usually showing a positive (latency about 200 msec)--negative(5--600msec)--positive(1000msec) sequence. This ERP appeared in all the stimulus conditions; its presence or absence, furthermore, was correlated with whether or not the baby seemed interested in the stimuli. Four infants failed to produce these ERPs; an independent measure of attention to the stimuli, heart rate deceleration, was demonstrated in two of them. An electrode placed beneath the eye to monitor eye movements yielded ERPs closely resembling those derived from the scalp in most subjects; reasons are given for assigning this response to activity in the brain, probably at the frontal pole. This study appears to be one of the first to search for cognitive 'late waves' in a no-task situation. The results suggest that further work with such task-free paradigms may yield additional useful techniques for studying the ERP.

  12. Brain metabolite concentrations across cortical regions in healthy adults

    PubMed Central

    Bracken, Bethany K.; Jensen, J. Eric; Prescot, Andrew P.; Cohen, Bruce M.; Renshaw, Perry F.; Öngür, Dost

    2010-01-01

    Magnetic resonance spectroscopy (MRS) can provide in vivo information about metabolite levels across multiple brain regions. This study used MRS to examine concentrations of N-acetylaspartate (NAA), a marker of neuronal integrity and function, and choline (Cho) which is related to the amount of cell membrane per unit volume, in anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) in healthy individuals. Data were drawn from two experiments which examined glutamatergic and GABAergic signaling in schizophrenia and bipolar disorder. After controlling for gray matter percentages, NAA/Creatine (Cr) was 18% higher in POC than in ACC (p<0.001); Cho/Cr was 46% lower in POC than in ACC (p<0.001). There was an effect of study (p<0.001 for both metabolites), but no region by study interaction (NAA p=0.101, Cho p=0.850). Since NAA is localized to the intracellular space, these data suggest that ACC neuronal compartment is reduced as compared with POC, or that there is a lower concentration of NAA per cell in the ACC than POC, or both. Since elevated Cho suggests more cell membrane per unit volume, reduced NAA in ACC appears to be coupled with increases in overall cell membrane compartment. These findings are consistent with a number of previous studies using proton MRS which found increasing NAA and decreasing Cho moving caudally, and with post mortem anatomical studies which found neurons in more widely spaced bundles in ACC when compared to parietal and occipital cortices. MRS may be a useful tool for studying physical properties of the living human brain. PMID:21081116

  13. Correlations between Brain Cortical Thickness and Cutaneous Pain Thresholds Are Atypical in Adults with Migraine

    PubMed Central

    Schwedt, Todd J.; Chong, Catherine D.

    2014-01-01

    Background/Objective Migraineurs have atypical pain processing, increased expectations for pain, and hypervigilance for pain. Recent studies identified correlations between brain structure and pain sensation in healthy adults. The objective of this study was to compare cortical thickness-to-pain threshold correlations in migraineurs to healthy controls. We hypothesized that migraineurs would have aberrant relationships between the anatomical neurocorrelates of pain processing and pain thresholds. Methods Pain thresholds to cutaneously applied heat were determined for 31 adult migraineurs and 32 healthy controls. Cortical thickness was determined from magnetic resonance imaging T1-weighted sequences. Regional cortical thickness-to-pain threshold correlations were determined for migraineurs and controls separately using a general linear model whole brain vertex-wise analysis. A pain threshold-by-group interaction analysis was then conducted to estimate regions where migraineurs show alterations in the pain threshold-to-cortical thickness correlations relative to healthy controls. Results Controls had negative correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left posterior cingulate/precuneus, right superior temporal, right inferior parietal, and left inferior temporal regions, and a negative correlation (p<0.01 Monte Carlo corrected) with a left superior temporal/inferior parietal region. Migraineurs had positive correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left superior temporal/inferior parietal, right precuneus, right superior temporal/inferior parietal, and left inferior parietal regions. Cortical thickness-to-pain threshold correlations differed between migraine and control groups (p<0.01 uncorrected) for right superior temporal/inferior parietal, right precentral, left posterior cingulate/precuneus, and right inferior parietal regions and (p<0.01 Monte Carlo corrected) for a left superior

  14. Functional Connectivity in Multiple Cortical Networks Is Associated with Performance Across Cognitive Domains in Older Adults

    PubMed Central

    Shaw, Emily E.; Schultz, Aaron P.; Sperling, Reisa A.

    2015-01-01

    Abstract Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65–90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging. PMID:25827242

  15. Underarousal in Adult ADHD: How Are Peripheral and Cortical Arousal Related?

    PubMed

    Mayer, Kerstin; Wyckoff, Sarah Nicole; Strehl, Ute

    2016-07-01

    In children and adults with attention deficit/hyperactivity disorder (ADHD), a general slowing of spontaneous electroencephalographic (EEG) brain activity and a decrease of event-related potential amplitudes such as the contingent negative variation (CNV) are observed. Additionally, some studies have reported decreased skin conductance level (SCL) in this clinical population leading to the hypothesis of a peripheral hypoarousal, which may be a target of biofeedback treatment in addition to or instead of neurofeedback. To our knowledge, the relationship between SCL and CNV has not been simultaneously investigated in one experiment. Using the theoretical background of the hypoarousal model, this article aims to gain more insight into the differences and correlations of cortical (CNV) and peripheral (SCL) arousal in adults with ADHD. A sample of 23 adults with ADHD and 22 healthy controls underwent an auditory Go-NoGo task with simultaneous 22-channel EEG and SCL recordings. Reaction time (RT) and reaction time variability (RTV) were also measured to assess task performance. Significantly decreased CNV amplitude and significantly higher RTV were observed in the ADHD group, reflecting cortical underarousal and problems with sustained attention. No significant correlation between peripheral underarousal and cortical underarousal was observed in the ADHD group or the control group. The observed cortical underarousal reflected in the decreased CNV supports the notion of a reduced CNV amplitude as a possible biomarker for ADHD. However, the connection between cortical and peripheral arousal is not as clear as is suggested in previous research investigating both separately. Implications of these results for new treatment options for ADHD such as biofeedback are discussed.

  16. Switching roles: the functional plasticity of adult tissue stem cells

    PubMed Central

    Wabik, Agnieszka; Jones, Philip H

    2015-01-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  17. Adult stem cell plasticity: will engineered tissues be rejected?

    PubMed Central

    Fang, Te-Chao; Alison, Malcolm R; Wright, Nicholas A; Poulsom, Richard

    2004-01-01

    The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype. PMID:15255965

  18. Greater cortical thinning in normal older adults predicts later cognitive impairment

    PubMed Central

    Pacheco, Jennifer; Goh, Joshua O.; Kraut, Michael A.; Ferrucci, Luigi; Resnick, Susan M.

    2014-01-01

    Cross-sectional studies have shown regional differences in cortical thickness between healthy older adults and patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI). We now demonstrate that participants who subsequently develop cognitive impairment leading to a diagnosis of MCI or AD (n=25) experience greater cortical thinning in specific neuroanatomical regions compared to control participants who remained cognitively normal (n=96). Based on 8 years of annual MRI scans beginning an average of 11 years prior to onset of cognitive impairment, participants who developed cognitive impairment subsequent to the scanning period had greater longitudinal cortical thinning in the temporal poles and left medial temporal lobe compared to controls. No significant regional cortical thickness differences were found at baseline between the two study groups indicating that we are capturing a critical time when brain changes occur before behavioral manifestations of impairment are detectable. Our findings suggest that early events of the pathway that leads to cognitive impairment may involve the temporal lobe, and that this increased atrophy could be considered an early biomarker of neurodegeneration predictive of cognitive impairment years later. PMID:25311277

  19. Phonetically Irregular Word Pronunciation and Cortical Thickness in the Adult Brain

    PubMed Central

    Blackmon, Karen; Barr, William B.; Kuzniecky, Ruben; DuBois, Jonathan; Carlson, Chad; Quinn, Brian T.; Blumberg, Mark; Halgren, Eric; Hagler, Donald J.; Mikhly, Mark; Devinsky, Orrin; McDonald, Carrie R.; Dale, Anders M.; Thesen, Thomas

    2010-01-01

    Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to–phonemic conversion. PMID:20302944

  20. Effects of Consonant-Vowel Transitions in Speech Stimuli on Cortical Auditory Evoked Potentials in Adults

    PubMed Central

    Doellinger, Michael; Burger, Martin; Hoppe, Ulrich; Bosco, Enrico; Eysholdt, Ulrich

    2011-01-01

    We examined the neural activation to consonant-vowel transitions by cortical auditory evoked potentials (AEPs). The aim was to show whether cortical response patterns to speech stimuli contain components due to one of the temporal features, the voice-onset time (VOT). In seven normal-hearing adults, the cortical responses to four different monosyllabic words were opposed to the cortical responses to noise stimuli with the same temporal envelope as the speech stimuli. Significant hemispheric asymmetries were found for speech but not in noise evoked potentials. The difference signals between the AEPs to speech and corresponding noise stimuli revealed a significant negative component, which correlated with the VOT. The hemispheric asymmetries can be referred to rapid spectral changes. The correlation with the VOT indicates that the significant component in the difference signal reflects the perception of the acoustic change within the consonant-vowel transition. Thus, at the level of automatic processing, the characteristics of speech evoked potentials appear to be determined primarily by temporal aspects of the eliciting stimuli. PMID:21643536

  1. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    PubMed Central

    Cardin, Velia

    2016-01-01

    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  2. Differential effects of motor cortical excitability and plasticity in young and old individuals: a Transcranial Magnetic Stimulation (TMS) study.

    PubMed

    Bashir, Shahid; Perez, Jennifer M; Horvath, Jared C; Pena-Gomez, Cleofe; Vernet, Marine; Capia, Anuhya; Alonso-Alonso, Miguel; Pascual-Leone, Alvaro

    2014-01-01

    Aging is associated with changes in the motor system that, over time, can lead to functional impairments and contribute negatively to the ability to recover after brain damage. Unfortunately, there are still many questions surrounding the physiological mechanisms underlying these impairments. We examined cortico-spinal excitability and plasticity in a young cohort (age range: 19-31) and an elderly cohort (age range: 47-73) of healthy right-handed individuals using navigated transcranial magnetic stimulation (nTMS). Subjects were evaluated with a combination of physiological [motor evoked potentials (MEPs), motor threshold (MT), intracortical inhibition (ICI), intracortical facilitation (ICF), and silent period (SP)] and behavioral [reaction time (RT), pinch force, 9 hole peg task (HPT)] measures at baseline and following one session of low-frequency (1 Hz) navigated repetitive TMS (rTMS) to the right (non-dominant) hemisphere. In the young cohort, the inhibitory effect of 1 Hz rTMS was significantly in the right hemisphere and a significant facilitatory effect was noted in the unstimulated hemisphere. Conversely, in the elderly cohort, we report only a trend toward a facilitatory effect in the unstimulated hemisphere, suggesting reduced cortical plasticity and interhemispheric communication. To this effect, we show that significant differences in hemispheric cortico-spinal excitability were present in the elderly cohort at baseline, with significantly reduced cortico-spinal excitability in the right hemisphere as compared to the left hemisphere. A correlation analysis revealed no significant relationship between cortical thickness of the selected region of interest (ROI) and MEPs in either young or old subjects prior to and following rTMS. When combined with our preliminary results, further research into this topic could lead to the development of neurophysiological markers pertinent to the diagnosis, prognosis, and treatment of neurological diseases characterized

  3. 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.

  4. Emergent Spatial Patterns of Excitatory and Inhibitory Synaptic Strengths Drive Somatotopic Representational Discontinuities and their Plasticity in a Computational Model of Primary Sensory Cortical Area 3b.

    PubMed

    Grajski, Kamil A

    2016-01-01

    Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers), boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties. PMID:27504086

  5. Emergent Spatial Patterns of Excitatory and Inhibitory Synaptic Strengths Drive Somatotopic Representational Discontinuities and their Plasticity in a Computational Model of Primary Sensory Cortical Area 3b

    PubMed Central

    Grajski, Kamil A.

    2016-01-01

    Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers), boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties. PMID:27504086

  6. Cortical hypoplasia and ventriculomegaly of p73-deficient mice: Developmental and adult analysis.

    PubMed

    Medina-Bolívar, Carolina; González-Arnay, Emilio; Talos, Flaminia; González-Gómez, Miriam; Moll, Ute M; Meyer, Gundela

    2014-08-01

    Trp73, a member of the p53 gene family, plays a crucial role in neural development. We describe two main phenotypic variants of p73 deficiency in the brain, a severe one characterized by massive apoptosis in the cortex leading to early postnatal death and a milder, non-/low-apoptosis one in which 50% of pups may reach adulthood using an intensive-care breeding protocol. Both variants display the core triad of p73 deficiency: cortical hypoplasia, hippocampal malformations, and ventriculomegaly. We studied the development of the neocortex in p73 KO mice from early embryonic life into advanced age (25 months). Already at E14.5, the incipient cortical plate of the p73 KO brains showed a reduced width. Examination of adult neocortex revealed a generalized, nonprogressive reduction by 10-20%. Area-specific architectonic landmarks and lamination were preserved in all cortical areas. The surviving adult animals had moderate ventricular distension, whereas pups of the early lethal phenotypic variant showed severe ventriculomegaly. Ependymal cells of wild-type ventricles strongly express p73 and are particularly vulnerable to p73 deficiency. Ependymal denudation by apoptosis and reduction of ependymal cilia were already evident in young mice, with complete absence of cilia in older animals. Loss of p73 function in the ependyma may thus be one determining factor for chronic hydrocephalus, which leads to atrophy of subcortical structures (striatum, septum, amygdala). p73 Is thus involved in a variety of CNS activities ranging from embryonic regulation of brain size to the control of cerebrospinal fluid homeostasis in the adult brain via maintenance of the ependyma.

  7. Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

    PubMed Central

    Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

    2014-01-01

    Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

  8. Cortical plasticity within and across lifetimes: how can development inform us about phenotypic transformations?

    PubMed Central

    Krubitzer, Leah; Dooley, James C.

    2013-01-01

    The neocortex is the part of the mammalian brain that is involved in perception, cognition, and volitional motor control. It is a highly dynamic structure that is dramatically altered within the lifetime of an animal and in different lineages throughout the course of evolution. These alterations account for the remarkable variations in behavior that species exhibit. Of particular interest is how these cortical phenotypes change within the lifetime of the individual and eventually evolve in species over time. Because we cannot study the evolution of the neocortex directly we use comparative analysis to appreciate the types of changes that have been made to the neocortex and the similarities that exist across taxa. Developmental studies inform us about how these phenotypic transitions may arise by alterations in developmental cascades or changes in the physical environment in which the brain develops. Both genes and the sensory environment contribute to aspects of the phenotype and similar features, such as the size of a cortical field, can be altered in a variety of ways. Although both genes and the laws of physics place constraints on the evolution of the neocortex, mammals have evolved a number of mechanisms that allow them to loosen these constraints and often alter the course of their own evolution. PMID:24130524

  9. Observation of implied motion in a work of art modulates cortical connectivity and plasticity

    PubMed Central

    Concerto, Carmen; Infortuna, Carmenrita; Mineo, Ludovico; Pereira, Manuel; Freedberg, David; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

    2016-01-01

    Following the discovery of mirror neurons, much attention has been de-voted to understanding the neural responses evoked by observation of implied motion in works of art. Neuroimaging studies have demonstrated that dorsal premotor cortex (PMd) is commonly involved during observation of movements but the role of the inhibitory and excitatory connections between PMd and primary motor cortex (M1) during observation of implied motion remains uncertain. In this study, using high and low frequency repetitive transcranial magnetic stimulation (rTMS), we examined PMd–M1 connectivity and plasticity during observation of Michelangelo’s frescos with and without implied motion (Sistine Chapel, 1508–1512). We found that observation of implied motion in a painting specifically reduces the activity of inhibitory PMd–M1 connections. On the contrary PMd–M1 facilitatory connections, as examined by means of 5-Hz rTMS, were not modulated during observation of the painting. Our data suggest that observation of implied motion in a painting modulates PMd–M1 connectivity and plasticity. These results are consistent with the hypothesis that art with implied motion might be used as a plasticity-based intervention in rehabilitation. PMID:27807519

  10. Effect of a Gluten-Free Diet on Cortical Excitability in Adults with Celiac Disease

    PubMed Central

    Bella, Rita; Lanza, Giuseppe; Cantone, Mariagiovanna; Giuffrida, Salvatore; Puglisi, Valentina; Vinciguerra, Luisa; Pennisi, Manuela; Ricceri, Riccardo; D’Agate, Carmela Cinzia; Malaguarnera, Giulia; Ferri, Raffaele; Pennisi, Giovanni

    2015-01-01

    Introduction An imbalance between excitatory and inhibitory synaptic excitability was observed in de novo patients with celiac disease (CD) in a previous study with Transcranial Magnetic Stimulation (TMS), suggesting a subclinical involvement of GABAergic and glutamatergic neurotransmission in asymptomatic patients. The aim of this investigation was to monitor the eventual changes in the same cohort of patients, evaluated after a period of gluten-free diet. Methods Patients were re-evaluated after a median period of 16 months during which an adequate gluten-free diet was maintained. Clinical, cognitive and neuropsychiatric assessment was repeated, as well as cortical excitability by means of single- and paired-pulse TMS from the first dorsal interosseous muscle of the dominant hand. Results Compared to baseline, patients showed a significant decrease of the median resting motor threshold (from 35% to 33%, p<0.01). The other single-pulse (cortical silent period, motor evoked potentials latency and amplitude, central motor conduction time) and paired-pulse TMS measures (intracortical inhibition and intracortical facilitation) did not change significantly after the follow-up period. Antibodies were still present in 7 subjects. Discussion In patients under a gluten-free diet, a global increase of cortical excitability was observed, suggesting a glutamate-mediated functional reorganization compensating for disease progression. We hypothesize that glutamate receptor activation, probably triggered by CD-related immune system dysregulation, might result in a long-lasting motor cortex hyperexcitability with increased excitatory post-synaptic potentials, probably related to phenomena of long-term plasticity. The impact of the gluten-free diet on subclinical neurological abnormalities needs to be further explored. PMID:26053324

  11. Rapid functional reorganization of the forelimb cortical representation after thoracic spinal cord injury in adult rats.

    PubMed

    Sydekum, Esther; Ghosh, Arko; Gullo, Miriam; Baltes, Christof; Schwab, Martin; Rudin, Markus

    2014-02-15

    Thoracic spinal cord injured rats rely largely on forelimbs to walk, as their hindlimbs are dysfunctional. This increased limb use is accompanied by expansion of the cortical forelimb sensory representation. It is unclear how quickly the representational changes occur and whether they are at all related to the behavioral adaptation. Using blood oxygenation level dependent functional mangetic resonance imaging (BOLD-fMRI) we show that major plastic changes of the somato-sensory map can occur as early as one day after injury. The extent of map increase was variable between animals, and some animals showed a reduction in map size. However, at three or seven days after injury a significant enhancement of the forelimb representation was evident in all the animals. In a behavioral test for precise limb control, crossing of a horizontal ladder, the injured rats relied almost entirely on their forelimbs; they initially made more mistakes than at 7 days post injury. Remarkably, in the individual animals the behavioral performance seen at seven days was proportional to the physiological change present at one day after injury. The rapid increase in cortical representation of the injury-spared body part may provide the additional neural substrate necessary for high level behavioral adaptation. PMID:24185021

  12. A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor

    PubMed Central

    Bertini, Eva; Ribot, Jérôme; Di Nardo, Ariel A.; Volovitch, Michel; Prochiantz, Alain

    2016-01-01

    During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these “transfer” sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system. PMID:27171438

  13. Cortical plasticity for visuospatial processing and object recognition in deaf and hearing signers.

    PubMed

    Weisberg, Jill; Koo, Daniel S; Crain, Kelly L; Eden, Guinevere F

    2012-03-01

    Experience-dependent plasticity in deaf participants has been shown in a variety of studies focused on either the dorsal or ventral aspects of the visual system, but both systems have never been investigated in concert. Using functional magnetic resonance imaging (fMRI), we investigated functional plasticity for spatial processing (a dorsal visual pathway function) and for object processing (a ventral visual pathway function) concurrently, in the context of differing sensory (auditory deprivation) and language (use of a signed language) experience. During scanning, deaf native users of American Sign Language (ASL), hearing native ASL users, and hearing participants without ASL experience attended to either the spatial arrangement of frames containing objects or the identity of the objects themselves. These two tasks revealed the expected dorsal/ventral dichotomy for spatial versus object processing in all groups. In addition, the object identity matching task contained both face and house stimuli, allowing us to examine category-selectivity in the ventral pathway in all three participant groups. When contrasting the groups we found that deaf signers differed from the two hearing groups in dorsal pathway parietal regions involved in spatial cognition, suggesting sensory experience-driven plasticity. Group differences in the object processing system indicated that responses in the face-selective right lateral fusiform gyrus and anterior superior temporal cortex were sensitive to a combination of altered sensory and language experience, whereas responses in the amygdala were more closely tied to sensory experience. By selectively engaging the dorsal and ventral visual pathways within participants in groups with different sensory and language experiences, we have demonstrated that these experiences affect the function of both of these systems, and that certain changes are more closely tied to sensory experience, while others are driven by the combination of sensory and

  14. Video-Game Play Induces Plasticity in the Visual System of Adults with Amblyopia

    PubMed Central

    Li, Roger W.; Ngo, Charlie; Nguyen, Jennie; Levi, Dennis M.

    2011-01-01

    Abnormal visual experience during a sensitive period of development disrupts neuronal circuitry in the visual cortex and results in abnormal spatial vision or amblyopia. Here we examined whether playing video games can induce plasticity in the visual system of adults with amblyopia. Specifically 20 adults with amblyopia (age 15–61 y; visual acuity: 20/25–20/480, with no manifest ocular disease or nystagmus) were recruited and allocated into three intervention groups: action videogame group (n = 10), non-action videogame group (n = 3), and crossover control group (n = 7). Our experiments show that playing video games (both action and non-action games) for a short period of time (40–80 h, 2 h/d) using the amblyopic eye results in a substantial improvement in a wide range of fundamental visual functions, from low-level to high-level, including visual acuity (33%), positional acuity (16%), spatial attention (37%), and stereopsis (54%). Using a cross-over experimental design (first 20 h: occlusion therapy, and the next 40 h: videogame therapy), we can conclude that the improvement cannot be explained simply by eye patching alone. We quantified the limits and the time course of visual plasticity induced by video-game experience. The recovery in visual acuity that we observed is at least 5-fold faster than would be expected from occlusion therapy in childhood amblyopia. We used positional noise and modelling to reveal the neural mechanisms underlying the visual improvements in terms of decreased spatial distortion (7%) and increased processing efficiency (33%). Our study had several limitations: small sample size, lack of randomization, and differences in numbers between groups. A large-scale randomized clinical study is needed to confirm the therapeutic value of video-game treatment in clinical situations. Nonetheless, taken as a pilot study, this work suggests that video-game play may provide important principles for treating amblyopia, and perhaps

  15. Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case–Control Pilot Study

    PubMed Central

    Gilbert, Donald L.; Erickson, Craig A.; Horn, Paul S.; Shaffer, Rebecca C.; Wink, Logan K.; Laue, Cameron S.; Wu, Steve W.

    2016-01-01

    Abstract Objective: This case–control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. Methods: We studied youth with ASD aged 11–18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. Results: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. Conclusion: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of

  16. Plastic cup traps equipped with light-emitting diodes for monitoring adult Bemisia tabaci (Homoptera: Aleyrodidae).

    PubMed

    Chu, Chang-Chi; Jackson, Charles G; Alexander, Patrick J; Karut, Kamil; Henneberry, Thomas J

    2003-06-01

    Equipping the standard plastic cup trap, also known as the CC trap, with lime-green light-emitting diodes (LED-plastic cup trap) increased its efficacy for catching Bemisia tabaci by 100%. Few Eretmocerus eremicus Rose and Zolnerowich and Encarsia formosa Gahan were caught in LED-plastic cup traps. The LED-plastic cup traps are less expensive than yellow sticky card traps for monitoring adult whiteflies in greenhouse crop production systems and are more compatible with whitefly parasitoids releases for Bemisia nymph control.

  17. Cortical plasticity in 4-month-old infants: specific effects of experience with musical timbres.

    PubMed

    Trainor, Laurel J; Lee, Kathleen; Bosnyak, Daniel J

    2011-10-01

    Animal models suggest that the brain is particularly neuroplastic early in development, but previous studies have not systematically controlled the auditory environment in human infants and observed the effects on auditory cortical representations. We exposed 4-month-old infants to melodies in either guitar or marimba timbre (infants were randomly assigned to exposure group) for a total of ~160 min over the course of a week, after which we measured electroencephalogram (EEG) responses to guitar and marimba tones at pitches not previously heard during the exposure phase. A frontally negative response with a topography consistent with generation in auditory areas, peaking around 450 ms, was significantly larger for guitar than marimba tones in the guitar-exposed group but significantly larger for marimba than guitar tones in the marimba-exposed group. This indicates that experience with tones in a particular timbre affects representations for that timbre, and that this effect generalizes to tones not previously experienced during exposure. Furthermore, mismatch responses to occasional small 3% changes in pitch were larger for tones in guitar than marimba timbre only for infants exposed to guitar tones. Together these results indicate that a relatively small amount of passive exposure to a particular timbre in infancy enhances representations of that timbre and leads to more precise pitch processing for that timbre.

  18. Cortical plasticity in 4-month-old infants: specific effects of experience with musical timbres.

    PubMed

    Trainor, Laurel J; Lee, Kathleen; Bosnyak, Daniel J

    2011-10-01

    Animal models suggest that the brain is particularly neuroplastic early in development, but previous studies have not systematically controlled the auditory environment in human infants and observed the effects on auditory cortical representations. We exposed 4-month-old infants to melodies in either guitar or marimba timbre (infants were randomly assigned to exposure group) for a total of ~160 min over the course of a week, after which we measured electroencephalogram (EEG) responses to guitar and marimba tones at pitches not previously heard during the exposure phase. A frontally negative response with a topography consistent with generation in auditory areas, peaking around 450 ms, was significantly larger for guitar than marimba tones in the guitar-exposed group but significantly larger for marimba than guitar tones in the marimba-exposed group. This indicates that experience with tones in a particular timbre affects representations for that timbre, and that this effect generalizes to tones not previously experienced during exposure. Furthermore, mismatch responses to occasional small 3% changes in pitch were larger for tones in guitar than marimba timbre only for infants exposed to guitar tones. Together these results indicate that a relatively small amount of passive exposure to a particular timbre in infancy enhances representations of that timbre and leads to more precise pitch processing for that timbre. PMID:21445665

  19. Cortical plasticity, contingent negative variation, and transcendent experiences during practice of the Transcendental Meditation technique.

    PubMed

    Travis, F; Tecce, J J; Guttman, J

    2000-11-01

    This study investigated effects of transcendent experiences on contingent negative variation (CNV) amplitude, CNV rebound, and distraction effects. Three groups of age-matched subjects with few (<1 per year), more frequent (10-20 per year), or daily self-reported transcendent experiences received 31 simple RT trials (flash (S(1))/tone (S(2))/button press) followed by 31 divided-attention trials - randomly intermixed trials with or without a three-letter memory task in the S(1)-S(2) interval). Late CNV amplitudes in the simple trials were smallest in the group with fewest, and largest in the group with most frequent transcendent experiences. Conversely, CNV distraction effects were largest in the group with fewest and smallest in the group with most frequent transcendent experiences (the second group's values were in the middle in each case). These data suggest cumulative effects of transcendent experiences on cortical preparatory response (heightened late CNV amplitude in simple trials) and executive functioning (diminished distraction effects in letter trials).

  20. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia.

    PubMed

    Benussi, Alberto; Cosseddu, Maura; Filareto, Ilaria; Dell'Era, Valentina; Archetti, Silvana; Sofia Cotelli, Maria; Micheli, Anna; Padovani, Alessandro; Borroni, Barbara

    2016-09-01

    Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476. PMID:27438089

  1. Neurofeedback of slow cortical potentials: neural mechanisms and feasibility of a placebo-controlled design in healthy adults

    PubMed Central

    Gevensleben, Holger; Albrecht, Björn; Lütcke, Henry; Auer, Tibor; Dewiputri, Wan Ilma; Schweizer, Renate; Moll, Gunther; Heinrich, Hartmut; Rothenberger, Aribert

    2014-01-01

    To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials (SCPs) by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCPs training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post) fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT). Performance-data during the sessions (regulation performance) in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz) at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition. In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group

  2. Neurofeedback of slow cortical potentials: neural mechanisms and feasibility of a placebo-controlled design in healthy adults.

    PubMed

    Gevensleben, Holger; Albrecht, Björn; Lütcke, Henry; Auer, Tibor; Dewiputri, Wan Ilma; Schweizer, Renate; Moll, Gunther; Heinrich, Hartmut; Rothenberger, Aribert

    2014-01-01

    To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials (SCPs) by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCPs training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post) fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT). Performance-data during the sessions (regulation performance) in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz) at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition. In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group

  3. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    SciTech Connect

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  4. Sleep Duration and Subsequent Cortical Thinning in Cognitively Normal Older Adults

    PubMed Central

    Spira, Adam P.; Gonzalez, Christopher E.; Venkatraman, Vijay K.; Wu, Mark N.; Pacheco, Jennifer; Simonsick, Eleanor M.; Ferrucci, Luigi; Resnick, Susan M.

    2016-01-01

    Study Objectives: To determine the association between self-reported sleep duration and cortical thinning among older adults. Methods: We studied 122 cognitively normal participants in the Baltimore Longitudinal Study of Aging with a mean age = 66.6 y (range, 51–84) at baseline sleep assessment and 69.5 y (range, 56–86) at initial magnetic resonance imaging (MRI) scan. Participants reported average sleep duration and completed a mean of 7.6 1.5-T MRI scans (range, 3–11), with mean follow-up from initial scan of 8.0 y (range, 2.0–11.8). Results: In analyses adjusted for age, sex, education, race, and interval between sleep assessment and initial MRI scan, participants reporting > 7 h sleep at baseline had thinner cortex in the inferior occipital gyrus and sulcus of the left hemisphere at initial MRI scan than those reporting 7 h (cluster P < 0.05). In adjusted longitudinal analyses, compared to those reporting 7 h of sleep, participants reporting < 7 h exhibited higher rates of subsequent thinning in the superior temporal sulcus and gyrus, inferior and middle frontal gyrus, and superior frontal sulcus of the left hemisphere, and in the superior frontal gyrus of the right hemisphere; those reporting > 7 h of sleep had higher rates of thinning in the superior frontal and middle frontal gyrus of the left hemisphere (cluster P < 0.05 for all). In sensitivity analyses, adjustment for apolipoprotein E (APOE) e4 genotype reduced or eliminated some effects but revealed others. When reports of < 7 h of sleep were compared to reports of 7 or 8 h combined, there were no significant associations with cortical thinning. Conclusions: Among cognitively normal older adults, sleep durations of < 7 h and > 7 h may increase the rate of subsequent frontotemporal gray matter atrophy. Additional studies, including those that use objective sleep measures and investigate mechanisms linking sleep duration to gray matter loss, are needed. Citation: Spira AP, Gonzalez CE, Venkatraman

  5. Motor cortical plasticity in extrinsic hand muscles is determined by the resting thresholds of overlapping representations.

    PubMed

    Mirdamadi, J L; Suzuki, L Y; Meehan, S K

    2016-10-01

    Knowledge of the properties that govern the effectiveness of transcranial magnetic stimulation (TMS) interventions is critical to clinical application. Extrapolation to clinical populations has been limited by high inter-subject variability and a focus on intrinsic muscles of the hand in healthy populations. Therefore, the current study assessed variability of continuous theta burst stimulation (cTBS), a patterned TMS protocol, across an agonist-antagonist pair of extrinsic muscles of the hand. Secondarily, we assessed whether concurrent agonist contraction could enhance the efficacy of cTBS. Motor evoked potentials (MEP) were simultaneously recorded from the agonist flexor (FCR) and antagonist extensor (ECR) carpi radialis before and after cTBS over the FCR hotspot. cTBS was delivered with the FCR relaxed (cTBS-Relax) or during isometric wrist flexion (cTBS-Contract). cTBS-Relax suppressed FCR MEPs evoked from the FCR hotspot. However, the extent of FCR MEP suppression was strongly correlated with the relative difference between FCR and ECR resting motor thresholds. cTBS-Contract decreased FCR suppression but increased suppression of ECR MEPs elicited from the FCR hotspot. The magnitude of ECR MEP suppression following cTBS-Contract was independent of the threshold-amplitude relationships observed with cTBS-Relax. Contraction alone had no effect confirming the effect of cTBS-Contract was driven by the interaction between neuromuscular activity and cTBS. Interactions across muscle representations should be taken into account when predicting cTBS outcomes in healthy and clinical populations. Contraction during cTBS may be a useful means of focusing aftereffects when differences in baseline excitability across overlapping agonist-antagonist cortical representations may mitigate the inhibitory effect of cTBS.

  6. Motor cortical plasticity in extrinsic hand muscles is determined by the resting thresholds of overlapping representations.

    PubMed

    Mirdamadi, J L; Suzuki, L Y; Meehan, S K

    2016-10-01

    Knowledge of the properties that govern the effectiveness of transcranial magnetic stimulation (TMS) interventions is critical to clinical application. Extrapolation to clinical populations has been limited by high inter-subject variability and a focus on intrinsic muscles of the hand in healthy populations. Therefore, the current study assessed variability of continuous theta burst stimulation (cTBS), a patterned TMS protocol, across an agonist-antagonist pair of extrinsic muscles of the hand. Secondarily, we assessed whether concurrent agonist contraction could enhance the efficacy of cTBS. Motor evoked potentials (MEP) were simultaneously recorded from the agonist flexor (FCR) and antagonist extensor (ECR) carpi radialis before and after cTBS over the FCR hotspot. cTBS was delivered with the FCR relaxed (cTBS-Relax) or during isometric wrist flexion (cTBS-Contract). cTBS-Relax suppressed FCR MEPs evoked from the FCR hotspot. However, the extent of FCR MEP suppression was strongly correlated with the relative difference between FCR and ECR resting motor thresholds. cTBS-Contract decreased FCR suppression but increased suppression of ECR MEPs elicited from the FCR hotspot. The magnitude of ECR MEP suppression following cTBS-Contract was independent of the threshold-amplitude relationships observed with cTBS-Relax. Contraction alone had no effect confirming the effect of cTBS-Contract was driven by the interaction between neuromuscular activity and cTBS. Interactions across muscle representations should be taken into account when predicting cTBS outcomes in healthy and clinical populations. Contraction during cTBS may be a useful means of focusing aftereffects when differences in baseline excitability across overlapping agonist-antagonist cortical representations may mitigate the inhibitory effect of cTBS. PMID:27425211

  7. Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults

    PubMed Central

    Wilson, Tony W.; Heinrichs-Graham, Elizabeth; Becker, Katherine M.; Aloi, Joey; Robertson, Kevin R.; Sandkovsky, Uriel; White, Matthew L.; O’Neill, Jennifer; Knott, Nichole L.; Fox, Howard S.; Swindells, Susan

    2015-01-01

    Combination antiretroviral therapy transformed HIV-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in fronto-parietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually-matched controls completed 3-Tesla structural magnetic-resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data was examined using advanced beamforming methods, and sMRI data was analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially-coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker. PMID:25376125

  8. Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.

    PubMed

    Wilson, Tony W; Heinrichs-Graham, Elizabeth; Becker, Katherine M; Aloi, Joseph; Robertson, Kevin R; Sandkovsky, Uriel; White, Matthew L; O'Neill, Jennifer; Knott, Nichole L; Fox, Howard S; Swindells, Susan

    2015-03-01

    Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker.

  9. A Neurochemical Signature of Visual Recovery After Extrastriate Cortical Damage in the Adult Cat

    PubMed Central

    Huxlin, Krystel R.; Williams, Jennifer M.; Price, Tracy

    2010-01-01

    In adult cats, damage to the extrastriate visual cortex on the banks of the lateral suprasylvian (LS) sulcus causes severe deficits in motion perception that can recover as a result of intensive direction discrimination training. The fact that recovery is restricted to trained visual field locations suggests that the neural circuitry of early visual cortical areas, with their tighter retinotopy, may play an important role in attaining perceptual improvements after damage to higher level visual cortex. The present study tests this hypothesis by comparing the manner in which excitatory and inhibitory components of the supragranular circuitry in an early visual cortical area (area 18) are affected by LS lesions and postlesion training. First, the proportion of LS-projecting pyramidal cells as well as calbindin- and parvalbumin-positive interneurons expressing each of the four AMPA receptor subunits was estimated in layers II and III of area 18 in intact animals. The degree to which LS lesions and visual retraining altered these expression patterns was then assessed. Both LS-projecting pyramidal cells and inhibitory interneurons exhibited long-term, differential reductions in the expression of glutamate receptor (GluR)1, -2, -2/3, and -4 following LS lesions. Intensive visual training post lesion restored normal AMPAR subunit expression in all three cell-types examined. Furthermore, for LS-projecting and calbindin-positive neurons, this restoration occurred only in portions of the ipsi-lesional area 18 representing trained visual field locations. This supports our hypothesis that stimulation of early visual cortical areas—in this case, area 18—by training is an important factor in restoring visual perception after permanent damage to LS cortex. PMID:18300259

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

    PubMed Central

    Webb, Carol F.; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    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. PMID:26111446

  11. Effects of broadband noise on cortical evoked auditory responses at different loudness levels in young adults.

    PubMed

    Sharma, Mridula; Purdy, Suzanne C; Munro, Kevin J; Sawaya, Kathleen; Peter, Varghese

    2014-03-26

    Young adults with no history of hearing concerns were tested to investigate their /da/-evoked cortical auditory evoked potentials (P1-N1-P2) recorded from 32 scalp electrodes in the presence and absence of noise at three different loudness levels (soft, comfortable, and loud), at a fixed signal-to-noise ratio (+3 dB). P1 peak latency significantly increased at soft and loud levels, and N1 and P2 latencies increased at all three levels in the presence of noise, compared with the quiet condition. P1 amplitude was significantly larger in quiet than in noise conditions at the loudest level. N1 amplitude was larger in quiet than in noise for the soft level only. P2 amplitude was reduced in the presence of noise to a similar degree at all loudness levels. The differential effects of noise on P1, N1, and P2 suggest differences in auditory processes underlying these peaks. The combination of level and signal-to-noise ratio should be considered when using cortical auditory evoked potentials as an electrophysiological indicator of degraded speech processing.

  12. Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15.

    PubMed

    Picard, Nathalie; Leslie, Jennifer H; Trowbridge, Sara K; Subramanian, Jaichandar; Nedivi, Elly; Fagiolini, Michela

    2014-03-01

    During development, experience plays a crucial role in sculpting neuronal connections. Patterned neural activity guides formation of functional neural circuits through the selective stabilization of some synapses and the pruning of others. Activity-regulated factors are fundamental to this process, but their roles in synapse stabilization and maturation is still poorly understood. CPG15, encoded by the activity-regulated gene candidate plasticity gene 15, is a small, glycosylphosphatidylinositol (GPI)-linked, extracellular protein that promotes synapse stabilization. Here we show that global knock-out of cpg15 results in abnormal postnatal development of the excitatory network in visual cortex and an associated disruption in development of visual receptive field properties. In addition, whereas repeated stimulation induced potentiation and depression in wild-type mice, the depression was slower in cpg15 knock-out mice, suggesting impairment in short-term depression-like mechanisms. These findings establish the requirement for cpg15 in activity-dependent development of the visual system and demonstrate the importance of timely excitatory network development for normal visual function. PMID:24599452

  13. Aberrant Development and Plasticity of Excitatory Visual Cortical Networks in the Absence of cpg15

    PubMed Central

    Picard, Nathalie; Leslie, Jennifer H.; Trowbridge, Sara K.; Subramanian, Jaichandar; Nedivi, Elly

    2014-01-01

    During development, experience plays a crucial role in sculpting neuronal connections. Patterned neural activity guides formation of functional neural circuits through the selective stabilization of some synapses and the pruning of others. Activity-regulated factors are fundamental to this process, but their roles in synapse stabilization and maturation is still poorly understood. CPG15, encoded by the activity-regulated gene candidate plasticity gene 15, is a small, glycosylphosphatidylinositol (GPI)-linked, extracellular protein that promotes synapse stabilization. Here we show that global knock-out of cpg15 results in abnormal postnatal development of the excitatory network in visual cortex and an associated disruption in development of visual receptive field properties. In addition, whereas repeated stimulation induced potentiation and depression in wild-type mice, the depression was slower in cpg15 knock-out mice, suggesting impairment in short-term depression-like mechanisms. These findings establish the requirement for cpg15 in activity-dependent development of the visual system and demonstrate the importance of timely excitatory network development for normal visual function. PMID:24599452

  14. 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

  15. Music-induced cortical plasticity and lateral inhibition in the human auditory cortex as foundations for tonal tinnitus treatment

    PubMed Central

    Pantev, Christo; Okamoto, Hidehiko; Teismann, Henning

    2012-01-01

    Over the past 15 years, we have studied plasticity in the human auditory cortex by means of magnetoencephalography (MEG). Two main topics nurtured our curiosity: the effects of musical training on plasticity in the auditory system, and the effects of lateral inhibition. One of our plasticity studies found that listening to notched music for 3 h inhibited the neuronal activity in the auditory cortex that corresponded to the center-frequency of the notch, suggesting suppression of neural activity by lateral inhibition. Subsequent research on this topic found that suppression was notably dependent upon the notch width employed, that the lower notch-edge induced stronger attenuation of neural activity than the higher notch-edge, and that auditory focused attention strengthened the inhibitory networks. Crucially, the overall effects of lateral inhibition on human auditory cortical activity were stronger than the habituation effects. Based on these results we developed a novel treatment strategy for tonal tinnitus—tailor-made notched music training (TMNMT). By notching the music energy spectrum around the individual tinnitus frequency, we intended to attract lateral inhibition to auditory neurons involved in tinnitus perception. So far, the training strategy has been evaluated in two studies. The results of the initial long-term controlled study (12 months) supported the validity of the treatment concept: subjective tinnitus loudness and annoyance were significantly reduced after TMNMT but not when notching spared the tinnitus frequencies. Correspondingly, tinnitus-related auditory evoked fields (AEFs) were significantly reduced after training. The subsequent short-term (5 days) training study indicated that training was more effective in the case of tinnitus frequencies ≤ 8 kHz compared to tinnitus frequencies >8 kHz, and that training should be employed over a long-term in order to induce more persistent effects. Further development and evaluation of TMNMT therapy

  16. A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Greifzu, Franziska; Löwel, Siegrid

    2015-01-01

    It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold ("visual acuity") nor of the contrast threshold ("contrast sensitivity") of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions.

  17. A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Greifzu, Franziska; Löwel, Siegrid

    2015-01-01

    It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold ("visual acuity") nor of the contrast threshold ("contrast sensitivity") of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions

  18. Chronic Deep Cerebellar Stimulation Promotes Long-Term Potentiation, Microstructural Plasticity, and Reorganization of Perilesional Cortical Representation in a Rodent Model

    PubMed Central

    Cooperrider, Jessica; Furmaga, Havan; Plow, Ela; Park, Hyun-Joo; Chen, Zhihong; Kidd, Grahame; Baker, Kenneth B.; Gale, John T.

    2014-01-01

    Control over postinjury CNS plasticity is a major frontier of science that, if conquered, would open new avenues for treatment of neurological disorders. Here we investigate the functional, physiological, and structural changes in the cerebral cortex associated with chronic deep brain stimulation of the cerebellar output, a treatment approach that has been shown to improve postischemia motor recovery in a rodent model of cortical infarcts. Long–Evans rats were pretrained on the pasta-matrix retrieval task, followed by induction of focal cortical ischemia and implantation of a macroelectrode in the contralesional lateral cerebellar nucleus. Animals were assigned to one of three treatment groups pseudorandomly to balance severity of poststroke motor deficits: REGULAR stimulation, BURST stimulation, or SHAM. Treatment initiated 2 weeks post surgery and continued for 5 weeks. At the end, animals were randomly selected for perilesional intracortical microstimulation mapping and tissue sampling for Western blot analysis or contributed tissue for 3D electron microscopy. Evidence of enhanced cortical plasticity with therapeutically effective stimulation is shown, marked by greater perilesional reorganization in stimulation- treated animals versus SHAM. BURST stimulation was significantly effective for promoting distal forepaw cortical representation. Stimulation-treated animals showed a twofold increase in synaptic density compared with SHAM. In addition, treated animals demonstrated increased expression of synaptic markers of long-term potentiation and plasticity, including synaptophysin, NMDAR1, CaMKII, and PSD95. These findings provide a critical foundation of how deep cerebellar stimulation may guide plastic reparative reorganization after nonprogressive brain injury and indicate strong translational potential. PMID:24990924

  19. Longitudinal Changes in White Matter Tract Integrity across the Adult Lifespan and Its Relation to Cortical Thinning

    PubMed Central

    Fjell, Anders M.; Yendiki, Anastasia; Walhovd, Kristine B.

    2016-01-01

    A causal link between decreases in white matter (WM) integrity and cortical degeneration is assumed, but there is scarce knowledge on the relationship between these changes across the adult human lifespan. We investigated changes in thickness throughout the cortical mantle and WM tract integrity derived from T1 and diffusion weighted magnetic resonance imaging (MRI) scans in 201 healthy adults aged 23–87 years over a mean interval of 3.6 years. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivity changes were calculated for forceps minor and major and eight major white matter tracts in each hemisphere by use of a novel automated longitudinal tractography constrained by underlying anatomy (TRACULA) approach. We hypothesized that increasing MD and decreasing FA across tracts would relate to cortical thinning, with some anatomical specificity. WM integrity decreased across tracts non-uniformly, with mean annual percentage decreases ranging from 0.20 in the Inferior Longitudinal Fasciculus to 0.65 in the Superior Longitudinal Fasciculus. For most tracts, greater MD increases and FA decreases related to more cortical thinning, in areas in part overlapping with but also outside the projected tract endings. The findings indicate a combination of global and tract-specific relationships between WM integrity and cortical thinning. PMID:27253393

  20. Slow-Frequency Pulsed Transcranial Electrical Stimulation for Modulation of Cortical Plasticity Based on Reciprocity Targeting with Precision Electrical Head Modeling

    PubMed Central

    Luu, Phan; Essaki Arumugam, Easwara Moorthy; Anderson, Erik; Gunn, Amanda; Rech, Dennis; Turovets, Sergei; Tucker, Don M.

    2016-01-01

    In pain management as well as other clinical applications of neuromodulation, it is important to consider the timing parameters influencing activity-dependent plasticity, including pulsed versus sustained currents, as well as the spatial action of electrical currents as they polarize the complex convolutions of the cortical mantle. These factors are of course related; studying temporal factors is not possible when the spatial resolution of current delivery to the cortex is so uncertain to make it unclear whether excitability is increased or decreased with anodal vs. cathodal current flow. In the present study we attempted to improve the targeting of specific cortical locations by applying current through flexible source-sink configurations of 256 electrodes in a geodesic array. We constructed a precision electric head model for 12 healthy individuals. Extraction of the individual’s cortical surface allowed computation of the component of the induced current that is normal to the target cortical surface. In an effort to replicate the long-term depression (LTD) induced with pulsed protocols in invasive animal research and transcranial magnetic stimulation studies, we applied 100 ms pulses at 1.9 s intervals either in cortical-surface-anodal or cortical-surface-cathodal directions, with a placebo (sham) control. The results showed significant LTD of the motor evoked potential as a result of the cortical-surface-cathodal pulses in contrast to the placebo control, with a smaller but similar LTD effect for anodal pulses. The cathodal LTD after-effect was sustained over 90 min following current injection. These results support the feasibility of pulsed protocols with low total charge in non-invasive neuromodulation when the precision of targeting is improved with a dense electrode array and accurate head modeling. PMID:27531976

  1. Slow-Frequency Pulsed Transcranial Electrical Stimulation for Modulation of Cortical Plasticity Based on Reciprocity Targeting with Precision Electrical Head Modeling.

    PubMed

    Luu, Phan; Essaki Arumugam, Easwara Moorthy; Anderson, Erik; Gunn, Amanda; Rech, Dennis; Turovets, Sergei; Tucker, Don M

    2016-01-01

    In pain management as well as other clinical applications of neuromodulation, it is important to consider the timing parameters influencing activity-dependent plasticity, including pulsed versus sustained currents, as well as the spatial action of electrical currents as they polarize the complex convolutions of the cortical mantle. These factors are of course related; studying temporal factors is not possible when the spatial resolution of current delivery to the cortex is so uncertain to make it unclear whether excitability is increased or decreased with anodal vs. cathodal current flow. In the present study we attempted to improve the targeting of specific cortical locations by applying current through flexible source-sink configurations of 256 electrodes in a geodesic array. We constructed a precision electric head model for 12 healthy individuals. Extraction of the individual's cortical surface allowed computation of the component of the induced current that is normal to the target cortical surface. In an effort to replicate the long-term depression (LTD) induced with pulsed protocols in invasive animal research and transcranial magnetic stimulation studies, we applied 100 ms pulses at 1.9 s intervals either in cortical-surface-anodal or cortical-surface-cathodal directions, with a placebo (sham) control. The results showed significant LTD of the motor evoked potential as a result of the cortical-surface-cathodal pulses in contrast to the placebo control, with a smaller but similar LTD effect for anodal pulses. The cathodal LTD after-effect was sustained over 90 min following current injection. These results support the feasibility of pulsed protocols with low total charge in non-invasive neuromodulation when the precision of targeting is improved with a dense electrode array and accurate head modeling. PMID:27531976

  2. Characterizing Brain Cortical Plasticity and Network Dynamics Across the Age-Span in Health and Disease with TMS-EEG and TMS-fMRI

    PubMed Central

    Pascual-Leone, Alvaro; Freitas, Catarina; Oberman, Lindsay; Horvath, Jared C.; Halko, Mark; Eldaief, Mark; Bashir, Shahid; Vernet, Marine; Shafi, Mouhshin; Westover, Brandon; Vahabzadeh-Hagh, Andrew M.; Rotenberg, Alexander

    2012-01-01

    Brain plasticity can be conceptualized as nature’s invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the life-span. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable ‘starting-points’ and different ‘slopes of change’ defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer’s disease. PMID:21842407

  3. 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.

  4. Spatial integration and cortical dynamics.

    PubMed Central

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-01

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8570604

  5. 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…

  6. 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…

  7. Histochemical changes in cytochrome oxidase of cortical barrels after vibrissal removal in neonatal and adult mice.

    PubMed Central

    Wong-Riley, M T; Welt, C

    1980-01-01

    The posteromedial barrel subfield of the somatosensory cortex of mice was examined histochemically for cytochrome oxidase activity (cytochrome c oxidase; ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). In normal mice a high enzymatic activity was found within the barrel hollows, rather than in the sides and septa. Electron microscopic examination indicated that within the hollows reactive mitochondria reside in many dendrites, in some axonal terminals, and in a few neuronal perikarya. After neonatal cauterization of selected row(s) of vibrissae, the corresponding row(s) of barrels appeared as narrowed fused band(s) and their cytochrome oxidase activity was much reduced. Removal of vibrissae in the adult, by either cauterization or repeated plucking, did not cause size changes of cortical barrels. However, there was a significant decrease in the oxidative enzymatic activity within these barrels. Thus, the deprivation of sensory input through damage to, or removal of, the peripheral sensory organ induces an enzymatic response in neurons that are at least two to three synapses away from the periphery. Images PMID:6246540

  8. Age and dark rearing bidirectionally regulate the level and laminar pattern of expression of Abelson interacting protein 2 (Abi-2): a novel candidate visual cortical plasticity gene.

    PubMed

    Yang, Cui Bo; Kiser, Paul J; Zheng, Yu Ting; Mower, George D

    2013-11-01

    Electrophysiological studies indicate that cat visual cortical critical period neuronal plasticity peaks around 5 weeks and largely disappears by 20 weeks. Dark rearing slows this time course. Normal cats are more plastic than dark-reared cats at 5 weeks, but the opposite is true at 20 weeks. Thus, a stringent criterion for identifying genes controlling neuronal plasticity is that normal and dark rearing produce opposite direction differences in expression between young and older animals. Differential display polymerase chain reaction identified Abelson interacting protein 2 (Abi-2) as a candidate plasticity gene regulated according to this criterion. Western blotting showed bidirectional regulation of Abi-2 protein levels in cats and mice that was specific to visual cortex and did not occur in frontal cortex. Immunohistochemistry indicated developmental changes in Abi-2 laminar expression in cat visual cortex. Dark rearing altered laminar expression such that at 5 weeks, dark-reared cats were similar to 1-week normally reared cats, and at 20 weeks, dark-reared cats were similar to 5-10-week normally reared animals. The effect of dark rearing on both Abi-2 expression levels and laminar expression patterns was to slow the normal developmental process, the same effect seen on physiologically assessed plasticity in visual cortex.

  9. Age and Dark Rearing Bidirectionally Regulate the Level and Laminar Pattern of Expression of Abelson Interacting Protein 2 (Abi-2), a Novel Candidate Visual Cortical Plasticity Gene

    PubMed Central

    Yang, Cui Bo; Kiser, Paul J.; Zheng, Yu Ting; Mower, George D.

    2013-01-01

    Electrophysiological studies indicate that cat visual cortical critical period neuronal plasticity peaks around 5 weeks and largely disappears by 20 weeks. Dark rearing slows this time course. Normal cats are more plastic than dark reared cats at 5 weeks but the opposite is true at 20 weeks. Thus, a stringent criterion for identifying genes controlling neuronal plasticity is that normal and dark rearing produce opposite direction differences in expression between young and older animals. Differential display PCR identified Abelson interacting protein 2 (Abi-2) as a candidate plasticity gene regulated according to this criterion. Western blotting showed bidirectional regulation of Abi-2 protein levels in cats and mice that was specific to visual cortex and did not occur in frontal cortex. Immunohistochemistry indicated developmental changes in Abi-2 laminar expression in cat visual cortex. Dark rearing altered laminar expression such that at 5 weeks dark reared cats were similar to 1 week normally reared cats and at 20 weeks, dark reared cats were similar to 5–10 week normally reared animals. The effect of dark rearing on both Abi-2 expression levels and laminar expression patterns was to slow the normal developmental process, the same effect seen on physiologically assessed plasticity in visual cortex. PMID:23828391

  10. Nogo Receptor Signaling Restricts Adult Neural Plasticity by Limiting Synaptic AMPA Receptor Delivery

    PubMed Central

    Jitsuki, Susumu; Nakajima, Waki; Takemoto, Kiwamu; Sano, Akane; Tada, Hirobumi; Takahashi-Jitsuki, Aoi; Takahashi, Takuya

    2016-01-01

    Experience-dependent plasticity is limited in the adult brain, and its molecular and cellular mechanisms are poorly understood. Removal of the myelin-inhibiting signaling protein, Nogo receptor (NgR1), restores adult neural plasticity. Here we found that, in NgR1-deficient mice, whisker experience-driven synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) insertion in the barrel cortex, which is normally complete by 2 weeks after birth, lasts into adulthood. In vivo live imaging by two-photon microscopy revealed more AMPAR on the surface of spines in the adult barrel cortex of NgR1-deficient than on those of wild-type (WT) mice. Furthermore, we observed that whisker stimulation produced new spines in the adult barrel cortex of mutant but not WT mice, and that the newly synthesized spines contained surface AMPAR. These results suggest that Nogo signaling limits plasticity by restricting synaptic AMPAR delivery in coordination with anatomical plasticity. PMID:26472557

  11. 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

  12. Effects of urethane on the response properties of visual cortical neurons in young adult and old cats.

    PubMed

    Peng, Qing-Song; Zhou, Jun; Shi, Xia-Ming; Hua, Guo-Peng; Hua, Tian-Miao

    2011-06-01

    Previous studies have shown that visual cortical neurons in old mammals exhibit higher spontaneous activity, higher responsiveness to visual stimuli, and lower selectivity for stimulus orientations and motion directions than did neurons in young adult counterparts. However, whether the responsive difference in cortical neurons between young and old animals resulted from different effects induced by anesthetics has remained unclear. To clarify this issue, we recorded the response properties of individual neurons in the primary visual cortex of old and young adult cats while systematically varying the anesthesia level of urethane, a widely used anesthetic in physiology experiments. Our results showed that cumulatively administrating 50 mg and 100 mg of urethane upon the minimal level of urethane required to anesthetize an old or young adult cat did not significantly alter the degree of neuronal response selectivity for stimulus orientations and motion directions nor significantly change the visually-driven response and spontaneous activity of neurons in old and young adult cats. Cumulatively administrating 150 mg of urethane decreased neuronal responsiveness similarly in both age groups. Therefore, urethane appears to exert similar effects on neuronal response properties of old and young adult animals. PMID:21698802

  13. All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis.

    PubMed

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

    2013-01-01

    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).

  14. 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

  15. Associations between cortical thickness and general intelligence in children, adolescents and young adults

    PubMed Central

    Menary, Kyle; Collins, Paul F.; Porter, James N.; Muetzel, Ryan; Olson, Elizabeth A.; Kumar, Vipin; Steinbach, Michael; Lim, Kelvin O.; Luciana, Monica

    2013-01-01

    Neuroimaging research indicates that human intellectual ability is related to brain structure including the thickness of the cerebral cortex. Most studies indicate that general intelligence is positively associated with cortical thickness in areas of association cortex distributed throughout both brain hemispheres. In this study, we performed a cortical thickness mapping analysis on data from 182 healthy typically developing males and females ages 9 to 24 years to identify correlates of general intelligence (g) scores. To determine if these correlates also mediate associations of specific cognitive abilities with cortical thickness, we regressed specific cognitive test scores on g scores and analyzed the residuals with respect to cortical thickness. The effect of age on the association between cortical thickness and intelligence was examined. We found a widely distributed pattern of positive associations between cortical thickness and g scores, as derived from the first unrotated principal factor of a factor analysis of Wechsler Abbreviated Scale of Intelligence (WASI) subtest scores. After WASI specific cognitive subtest scores were regressed on g factor scores, the residual score variances did not correlate significantly with cortical thickness in the full sample with age covaried. When participants were grouped at the age median, significant positive associations of cortical thickness were obtained in the older group for g-residualized scores on Block Design (a measure of visual-motor integrative processing) while significant negative associations of cortical thickness were observed in the younger group for g-residualized Vocabulary scores. These results regarding correlates of general intelligence are concordant with the existing literature, while the findings from younger versus older subgroups have implications for future research on brain structural correlates of specific cognitive abilities, as well as the cognitive domain specificity of behavioral

  16. Axonal plasticity is associated with motor recovery following amphetamine treatment combined with rehabilitation after brain injury in the adult rat.

    PubMed

    Ramic, Maya; Emerick, April J; Bollnow, Melanie R; O'Brien, Timothy E; Tsai, Shih-Yen; Kartje, Gwendolyn L

    2006-09-21

    Clinical and laboratory studies have suggested that amphetamine treatment when paired with rehabilitation results in improved recovery of function after stroke or traumatic brain injury. In the present study, we investigated whether new anatomical pathways developed in association with improved motor function after brain damage and amphetamine treatment linked with rehabilitation. Following a unilateral sensorimotor cortex lesion in the adult rat, amphetamine (2 mg/kg) was administered in conjunction with physiotherapy sessions on postoperative days two and five. Physiotherapy was continued twice daily for the first 3 weeks after injury, and then once daily until week six. Performance on skilled forelimb reaching and ladder rung walking was used to assess motor improvement. Our results show that animals with sensorimotor cortical lesions receiving amphetamine treatment linked with rehabilitation had significant improvement in both tasks. Neuroanatomical tracing of efferent pathways from the opposite, non-damaged cortex resulted in the novel finding that amphetamine treatment linked with rehabilitation, significantly increased axonal growth in the deafferented basilar pontine nuclei. These results support the notion that pharmacological interventions paired with rehabilitation can enhance neuronal plasticity and thereby improve functional recovery after CNS injury. PMID:16920088

  17. 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

  18. Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

    PubMed

    Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

    2014-06-18

    Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span. PMID:24948804

  19. Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

    PubMed

    Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

    2014-06-18

    Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span.

  20. Order-sensitive plasticity in adult primary auditory cortex

    PubMed Central

    Kilgard, Michael P.; Merzenich, Michael M.

    2002-01-01

    The neural response to a stimulus presented as part of a rapid sequence is often quite different from the response to the same stimulus presented in isolation. In primary auditory cortex (A1), although the most common effect of preceding stimuli is inhibitory, most neurons can also exhibit response facilitation if the appropriate spectral and temporal separation of sequence elements is presented. In this study, we investigated whether A1 neurons in adult animals can develop context-dependent facilitation to a novel acoustic sequence. After repeatedly pairing electrical stimulation of the basal forebrain with a three-element sequence (high frequency tone–low frequency tone– noise burst), 25% of A1 neurons exhibited facilitation to the low tone when preceded by the high tone, compared with only 5% in controls. In contrast, there was no increase in the percent of sites that showed facilitation for the reversed tone order (low preceding high). Nearly 60% of sites exhibited a facilitated response to the noise burst when preceded by the two tones. Although facilitation was greatest in response to the paired sequence, facilitation also generalized to related sequences that were either temporally distorted or missing one of the tones. Pairing basal forebrain stimulation with the acoustic sequence also caused a decrease in the time to peak response and an increase in population discharge synchrony, which was not seen after pairing simple tones, tone trains, or broadband stimuli. These results indicate that context-dependent facilitation and response synchronization can be substantially altered in an experience-dependent fashion and provide a potential mechanism for learning spectrotemporal patterns. PMID:11880653

  1. 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.

  2. Environmental enrichment extends ocular dominance plasticity into adulthood and protects from stroke-induced impairments of plasticity.

    PubMed

    Greifzu, Franziska; Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Krempler, Katja; Favaro, Plinio D; Schlüter, Oliver M; Löwel, Siegrid

    2014-01-21

    Ocular dominance (OD) plasticity in mouse primary visual cortex (V1) declines during postnatal development and is absent beyond postnatal day 110 if mice are raised in standard cages (SCs). An enriched environment (EE) promotes OD plasticity in adult rats. Here, we explored cellular mechanisms of EE in mouse V1 and the therapeutic potential of EE to prevent impairments of plasticity after a cortical stroke. Using in vivo optical imaging, we observed that monocular deprivation in adult EE mice (i) caused a very strong OD plasticity previously only observed in 4-wk-old animals, (ii) restored already lost OD plasticity in adult SC-raised mice, and (iii) preserved OD plasticity after a stroke in the primary somatosensory cortex. Using patch-clamp electrophysiology in vitro, we also show that (iv) local inhibition was significantly reduced in V1 slices of adult EE mice and (v) the GABA/AMPA ratio was like that in 4-wk-old SC-raised animals. These observations were corroborated by in vivo analyses showing that diazepam treatment significantly reduced the OD shift of EE mice after monocular deprivation. Taken together, EE extended the sensitive phase for OD plasticity into late adulthood, rejuvenated V1 after 4 mo of SC-rearing, and protected adult mice from stroke-induced impairments of cortical plasticity. The EE effect was mediated most likely by preserving low juvenile levels of inhibition into adulthood, which potentially promoted adaptive changes in cortical circuits. PMID:24395770

  3. Optical coherence tomography reveals in vivo cortical structures of adult rats in response to cerebral ischemia injury

    NASA Astrophysics Data System (ADS)

    Ni, Yi-rong; Guo, Zhou-yi; Shu, So-yun; Bao, Xin-min

    2008-12-01

    Optical coherence tomography(OCT) is a high resolution imaging technique which uses light to directly image living tissue. we investigate the potential use of OCT for structural imaging of the ischemia injury mammalian cerebral cortex. And we examine models of middle cerebral artery occlusion (MCAO) in rats in vivo using OCT. In particular, we show that OCT can perform in vivo detection of cortex and differentiate normal and abnormal cortical anatomy. This OCT system in this study provided an axial resolution of 10~15μ m, the transverse resolution of the system is about 25 μm. OCT can provide cross-sectional images of cortical of adult rats in response to cerebral ischemia injury.We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the cerebral cortex structures and may offer a new tool for Possible neuroscience clinical applications.

  4. 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. PMID:26948893

  5. 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. PMID:24992362

  6. 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.

  7. Olanzapine Treatment of Adolescent Rats Alters Adult D2 Modulation of Cortical Inputs to the Ventral Striatum

    PubMed Central

    Brooks, Julie M.; Frost, Douglas O.

    2016-01-01

    Background: The striatal dopamine system undergoes vast ontogenetic changes during adolescence, making the brain vulnerable to drug treatments that target this class of neurotransmitters. Atypical antipsychotic drugs are often prescribed to children and adolescents for off-label treatment of neuropsychiatric disorders, yet the long-term impact this treatment has on brain development remains largely unknown. Methods: Adolescent male rats were treated with olanzapine or vehicle for 3 weeks (during postnatal day 28–49) using a dosing condition designed to approximate closely D2 receptor occupancies in the human therapeutic range. We assessed D2 receptor modulation of corticostriatal inputs onto medium spiny neurons in the adult ventral striatum using in vitro whole-cell current clamp recordings. Results: The D2/D3 agonist quinpirole (5 µM) enhanced cortically driven medium spiny neuron synaptic responses in slices taken from adult rats treated with vehicle during adolescence, as in untreated adult rats. However, in slices from mature rats treated with olanzapine during adolescence, quinpirole reduced medium spiny neuron activation. The magnitude of decrease was similar to previous observations in untreated, prepubertal rats. These changes may reflect alterations in local inhibitory circuitry, as the GABA-A antagonist picrotoxin (100 µM) reversed the effects of quinpirole in vehicle-treated slices but had no impact on cortically evoked responses in olanzapine-treated slices. Conclusions: These data suggest that adolescent atypical antipsychotic drug treatment leads to enduring changes in dopamine modulation of corticostriatal synaptic function. PMID:27207908

  8. Corticomotor plasticity and learning of a ballistic thumb training task are diminished in older adults.

    PubMed

    Rogasch, Nigel C; Dartnall, Tamara J; Cirillo, John; Nordstrom, Michael A; Semmler, John G

    2009-12-01

    This study examined changes in corticomotor excitability and plasticity after a thumb abduction training task in young and old adults. Electromyographic (EMG) recordings were obtained from right abductor pollicis brevis (APB, target muscle) and abductor digiti minimi (ADM, control muscle) in 14 young (18-24 yr) and 14 old (61-82 yr) adults. The training task consisted of 300 ballistic abductions of the right thumb to maximize peak thumb abduction acceleration (TAAcc). Transcranial magnetic stimulation (TMS) of the left primary motor cortex was used to assess changes in APB and ADM motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before, immediately after, and 30 min after training. No differences in corticomotor excitability (resting and active TMS thresholds, MEP input-output curves) or SICI were observed in young and old adults before training. Motor training resulted in improvements in peak TAAcc in young (177% improvement, P < 0.001) and old (124%, P = 0.005) subjects, with greater improvements in young subjects (P = 0.002). Different thumb kinematics were observed during task performance, with increases in APB EMG related to improvements in peak TAAcc in young (r(2) = 0.46, P = 0.008) but not old (r(2) = 0.09, P = 0.3) adults. After training, APB MEPs were 50% larger (P < 0.001 compared with before) in young subjects, with no change after training in old subjects (P = 0.49), suggesting reduced use-dependent corticomotor plasticity with advancing age. These changes were specific to APB, because no training-related change in MEP amplitude was observed in ADM. No significant association was observed between change in APB MEP and improvement in TAAcc with training in individual young and old subjects. SICI remained unchanged after training in both groups, suggesting that it was not responsible for the diminished use-dependent corticomotor plasticity for this task in older adults.

  9. Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults.

    PubMed

    Hartberg, Cecilie Bhandari; Lawyer, Glenn; Nyman, Håkan; Jönsson, Erik G; Haukvik, Unn K; Saetre, Peter; Bjerkan, Petr S; Andreassen, Ole A; Hall, Håkan; Agartz, Ingrid

    2010-05-30

    Relationships between prefrontal and temporal lobe grey matter volumes as assessed by magnetic resonance imaging and neurocognitive test results have been reported in schizophrenia. This investigation aimed to localize brain regions where cortical thickness and neurocognitive performance were related, and investigate if such relationships might differ in schizophrenia patients and healthy controls. Sixty-seven patients with schizophrenia and 69 healthy controls were characterized by neurocognitive testing and by brain cortical thickness maps. Putative cortical thickness/cognitive score relationships were investigated with contrast analyses of general linear models for the combined sample. Regions in which relationships were present were further investigated for diagnostic interaction. In the combined sample, significant positive relationships were found between frontal, temporal and occipital regions and tests for verbal IQ, verbal learning and executive functions. Diagnostic interaction was found for the relationships between verbal IQ and the right temporo-occipital junction and the left middle occipital gyrus. In conclusion, the significant relationships between cortical thickness and neurocognitive performances were localized in brain areas known to be involved in cognition. The relationships were similar in patients and controls, except for the right temporo-occipital and left occipital cortical areas, indicating a disrupted structure-function relationship in patients with schizophrenia compared to healthy control subjects.

  10. Summary of the N1-P2 Cortical Auditory Evoked Potential to Estimate the Auditory Threshold in Adults.

    PubMed

    Lightfoot, Guy

    2016-02-01

    This article introduces the cortical auditory evoked potential (CAEP) and describes the use of the N1-P2 response complex as an objective predictor of hearing threshold in adults and older children. The generators of the CAEP are discussed together with issues of maturation, subject factors, and stimuli and recording parameters for use in the clinic. The basic methods for response identification are outlined and suggestions are made for determining the CAEP threshold. Clinical applications are introduced and the accuracy of the CAEP as an estimator of hearing threshold is given. Finally, a case study provides an example of the technique in the context of medicolegal assessment. PMID:27587918

  11. 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

  12. Cortical GluK1 kainate receptors modulate scratching in adult mice.

    PubMed

    Descalzi, Giannina; Chen, Tao; Koga, Kohei; Li, Xiang-Yao; Yamada, Kaori; Zhuo, Min

    2013-09-01

    Recent investigations into the mechanisms mediating itch transmission have focused on spinal mechanisms, whereas few studies have investigated the role of the cerebral cortex in itch-related behaviors. Human imaging studies show that several cortical regions are active in correspondence with itch, including the anterior cingulate cortex (ACC). We present here evidence of cortical modulation of pruritogen-induced scratching behavior. We combine pharmacological, genetic, and electrophysiological approaches to show that cortical GluK1-containing kainate (KA) receptors are involved in scratching induced by histamine and non-histamine-dependent itching stimuli. We further show that scratching corresponds with enhanced excitatory transmission in the ACC through KA receptor modulation of inhibitory circuitry. In addition, we found that inhibiting GluK1-containing KA receptors in the ACC also reduced behavioral nociceptive responses induced by formalin. Our results reveal a new role of the cortex in pruritogen-induced scratching. PMID:23786569

  13. Cortical tibial osteoperiosteal flap technique to achieve bony bridge in transtibial amputation: experience in nine adult patients.

    PubMed

    Mongon, Mauricio Leal; Piva, Felipe Alberto; Mistro Neto, Sylvio; Carvalho, Jose Andre; Belangero, William Dias; Livani, Bruno

    2013-04-01

    Amputation, especially of the lower limbs, is a surgical procedure that gives excellent results when conducted under the appropriate conditions. In 1949 Ertl developed a technique for transtibial osteomyoplastic amputation which restored the intraosseous pressure through canal obliteration and expanded the area of terminal support through a bony bridge between the fibula and distal tibia. The aim of this study was to investigate the effectiveness of a modification of the original Ertl's technique in which a cortical osteoperiosteal flap created from the tibia is used to form a bony bridge during transtibial amputation in adults. Nine patients underwent leg amputations with the cortical tibial osteoperiosteal flap technique for reconstruction of the stump. The average duration of follow-up was 30.8 (range, 18-41) months. The post-surgery examination included a clinical examination and radiography. A 6-min walk test (Enright in Respir Care 48(8):783-785, 2003) was performed in the 32nd week after amputation. At 24th week post-surgery, all patients had stumps that were painless and able to bear full weight through the end. The creation of a cortical osteoperiosteal flap from the tibia to the fibula during transtibial amputation is a safe and effective technique that provides a strong and painless terminal weight-bearing stump. This constitutes a useful option for young patients, athletes, and patients with high physical demands. PMID:23371841

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

    PubMed

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

    2016-02-18

    Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles. Here we use the Drosophila melanogaster intestine to investigate the nature and importance 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 uncovers the key role this identity has in controlling organ size, reproductive plasticity and 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 that 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 recognized. PMID:26887495

  15. 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

  16. 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

  17. Short-term Cortical Plasticity Associated With Feedback-Error Learning After Locomotor Training in a Patient With Incomplete Spinal Cord Injury

    PubMed Central

    Peters, Sue; Borich, Michael R.; Boyd, Lara A.; Lam, Tania

    2015-01-01

    Background and Purpose For rehabilitation strategies to be effective, training should be based on principles of motor learning, such as feedback-error learning, that facilitate adaptive processes in the nervous system by inducing errors and recalibration of sensory and motor systems. This case report suggests that locomotor resistance training can enhance somatosensory and corticospinal excitability and modulate resting-state brain functional connectivity in a patient with motor-incomplete spinal cord injury (SCI). Case Description The short-term cortical plasticity of a 31-year-old man who had sustained an incomplete SCI 9.5 years previously was explored in response to body-weight–supported treadmill training with velocity-dependent resistance applied with a robotic gait orthosis. The following neurophysiological and neuroimaging measures were recorded before and after training. Sensory evoked potentials were elicited by electrical stimulation of the tibial nerve and recorded from the somatosensory cortex. Motor evoked potentials were generated with transcranial magnetic stimulation applied over the tibialis anterior muscle representation in the primary motor cortex. Resting-state functional magnetic resonance imaging was performed to evaluate short-term changes in patterns of brain activity associated with locomotor training. Outcomes Somatosensory excitability and corticospinal excitability were observed to increase after locomotor resistance training. Motor evoked potentials increased (particularly at higher stimulation intensities), and seed-based resting-state functional magnetic resonance imaging analyses revealed increased functional connectivity strength in the motor cortex associated with the less affected side after training. Discussion The observations suggest evidence of short-term cortical plasticity in 3 complementary neurophysiological measures after one session of locomotor resistance training. Future investigation in a sample of people with

  18. 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.

  19. 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. PMID:26559149

  20. 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.

  1. 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

  2. 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

  3. Region-specific network plasticity in simulated and living cortical networks: comparison of the center of activity trajectory (CAT) with other statistics.

    PubMed

    Chao, Zenas C; Bakkum, Douglas J; Potter, Steve M

    2007-09-01

    Electrically interfaced cortical networks cultured in vitro can be used as a model for studying the network mechanisms of learning and memory. Lasting changes in functional connectivity have been difficult to detect with extracellular multi-electrode arrays using standard firing rate statistics. We used both simulated and living networks to compare the ability of various statistics to quantify functional plasticity at the network level. Using a simulated integrate-and-fire neural network, we compared five established statistical methods to one of our own design, called center of activity trajectory (CAT). CAT, which depicts dynamics of the location-weighted average of spatiotemporal patterns of action potentials across the physical space of the neuronal circuitry, was the most sensitive statistic for detecting tetanus-induced plasticity in both simulated and living networks. By reducing the dimensionality of multi-unit data while still including spatial information, CAT allows efficient real-time computation of spatiotemporal activity patterns. Thus, CAT will be useful for studies in vivo or in vitro in which the locations of recording sites on multi-electrode probes are important. PMID:17873432

  4. Region-specific network plasticity in simulated and living cortical networks: comparison of the center of activity trajectory (CAT) with other statistics

    NASA Astrophysics Data System (ADS)

    Chao, Zenas C.; Bakkum, Douglas J.; Potter, Steve M.

    2007-09-01

    Electrically interfaced cortical networks cultured in vitro can be used as a model for studying the network mechanisms of learning and memory. Lasting changes in functional connectivity have been difficult to detect with extracellular multi-electrode arrays using standard firing rate statistics. We used both simulated and living networks to compare the ability of various statistics to quantify functional plasticity at the network level. Using a simulated integrate-and-fire neural network, we compared five established statistical methods to one of our own design, called center of activity trajectory (CAT). CAT, which depicts dynamics of the location-weighted average of spatiotemporal patterns of action potentials across the physical space of the neuronal circuitry, was the most sensitive statistic for detecting tetanus-induced plasticity in both simulated and living networks. By reducing the dimensionality of multi-unit data while still including spatial information, CAT allows efficient real-time computation of spatiotemporal activity patterns. Thus, CAT will be useful for studies in vivo or in vitro in which the locations of recording sites on multi-electrode probes are important.

  5. Reorganization and plasticity in the adult brain during learning of motor skills.

    PubMed

    Doyon, Julien; Benali, Habib

    2005-04-01

    On the basis of brain imaging studies, Doyon and Ungerleider recently proposed a model describing the cerebral plasticity that occurs in both cortico-striatal and cortico-cerebellar systems of the adult brain during learning of new motor skilled behaviors. This theoretical framework makes several testable predictions with regards to the contribution of these neural systems based on the phase (fast, slow, consolidation, automatization, and retention) and nature of the motor learning processes (motor sequence versus motor adaptation) acquired through repeated practice. There has been recent behavioral, lesion and additional neuroimaging studies that have addressed the assumptions made in this theory that will help in the revision of this model.

  6. Acute plastic bowing of the forearm in adults: a report of two cases.

    PubMed

    Tada, K; Ikeda, K; Tsubouchi, H; Tomita, K

    2008-08-01

    We report 2 adult cases where the diagnosis of acute plastic bowing of the forearm was either delayed or missed. In a 21-year-old man, ulnar bowing was missed and fixation was not performed because the patient had no limitation to his range of movement or pain. In a 24-year-old woman, the presentation of bowing in both the ulna and radius was delayed and corrective osteotomy was necessary for restoration of full range of movement. Prompt diagnosis enables manual reposition for easy restoration of full range of movement. PMID:18725680

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

    PubMed

    Jiang, Mingchen C; Elbasiouny, Sherif M; Collins, William F; Heckman, C J

    2015-09-01

    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.

  8. 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

  9. Retinotopic map plasticity in adult cat visual cortex is accompanied by changes in Ca2+/calmodulin-dependent protein kinase II alpha autophosphorylation.

    PubMed

    Van den Bergh, G; Eysel, U T; Vandenbussche, E; Vandesande, F; Arckens, L

    2003-01-01

    In adult cats, the induction of homonymous binocular central retinal lesions causes a dramatic reorganization of the topographic map in the sensory-deprived region of the primary visual cortex. To investigate the possible involvement of the alpha-subunit of the calcium/calmodulin dependent protein kinase type II (alphaCaMKII) in this form of brain plasticity, we performed in situ hybridization and Western blotting experiments to analyze mRNA, protein and autophosphorylation levels of this multifunctional kinase. No differences in the mRNA or protein levels were observed between the central, sensory-deprived and the peripheral, non-deprived regions of area 17 of retinal lesion animals or between corresponding cortical regions of normal control animals. Western blotting with an alphaCaMKII threonine-286 phosphorylation-state specific antiserum consistently showed a small, albeit not significant, increase of alphaCaMKII autophosphorylation in the central versus the peripheral region of cortical area 17, and this both in normal subjects as well as in retinal lesion animals with a 3-day post-lesion survival time. In contrast, a post-lesion survival time of 14 days resulted in a alphaCaMKII autophosphorylation level that was four times higher in visually-deprived area 17 than in the non-deprived cortical region. This increased phosphorylation state is not a direct consequence of the decrease in visual activity in these neurons, because we would have expected to see a similar change at shorter or longer post-lesion survival times or in the visually deprived visual cortex of animals in which the left optic tract and the corpus callosum were surgically cut. No such changes were observed, leading to the conclusion that the phosphorylation changes observed at 14 days are related to a delayed reorganization of the retinotopic map of the striate cortex. PMID:12849747

  10. Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity.

    PubMed

    Knikou, Maria; Dixon, Luke; Santora, Danielle; Ibrahim, Mohamed M

    2015-09-01

    Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans. PMID:26108955

  11. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence.

    PubMed

    Parkash, Jyoti; Messina, Andrea; Langlet, Fanny; Cimino, Irene; Loyens, Anne; Mazur, Danièle; Gallet, Sarah; Balland, Eglantine; Malone, Samuel A; Pralong, François; Cagnoni, Gabriella; Schellino, Roberta; De Marchis, Silvia; Mazzone, Massimiliano; Pasterkamp, R Jeroen; Tamagnone, Luca; Prevot, Vincent; Giacobini, Paolo

    2015-01-01

    Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle.

  12. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence

    PubMed Central

    Parkash, Jyoti; Messina, Andrea; Langlet, Fanny; Cimino, Irene; Loyens, Anne; Mazur, Danièle; Gallet, Sarah; Balland, Eglantine; Malone, Samuel A.; Pralong, François; Cagnoni, Gabriella; Schellino, Roberta; De Marchis, Silvia; Mazzone, Massimiliano; Pasterkamp, R. Jeroen; Tamagnone, Luca; Prevot, Vincent; Giacobini, Paolo

    2015-01-01

    Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic–pituitary–gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle. PMID:25721933

  13. Molecular and neuronal plasticity mechanisms in the amygdala-prefrontal cortical circuit: implications for opiate addiction memory formation.

    PubMed

    Rosen, Laura G; Sun, Ninglei; Rushlow, Walter; Laviolette, Steven R

    2015-01-01

    The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related "trigger" memories that may persist for lengthy periods of time, even during abstinence, in both humans, and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall, and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway's ventral tegmental area (VTA) and nucleus accumbens (NAc) and can modulate dopamine (DA) transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modeling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK) and the Ca(2+)/calmodulin-dependent protein

  14. Adult plasticity in multisensory neurons: Short-term experience-dependent changes in the superior colliculus

    PubMed Central

    Yu, Liping; Stein, Barry E.; Rowland, Benjamin A.

    2010-01-01

    Multisensory neurons in the superior colliculus (SC) have the capability to integrate signals that belong to the same event, despite being conveyed by different senses. They develop this capability during early life as experience is gained with the statistics of cross-modal events. These adaptations prepare the SC to deal with the cross-modal events that are likely to be encountered throughout life. Here we found that neurons in the adult SC can also adapt to experience with sequentially-ordered cross-modal (visual-auditory or auditory-visual) cues, and that they do so over short periods of time (minutes), as if adapting to a particular stimulus configuration. This short-term plasticity was evident as a rapid increase in the magnitude and duration of responses to the first stimulus, and a shortening of the latency and increase in magnitude of the responses to the second stimulus when they are presented in sequence. The result was that the two responses appeared to merge. These changes were stable in the absence of experience with competing stimulus configurations, outlasted the exposure period, and could not be induced by equivalent experience with sequential within-modal (visual-visual or auditory-auditory) stimuli. A parsimonious interpretation is that the additional SC activity provided by the second stimulus became associated with, and increased the potency of, the afferents responding to the preceding stimulus. This interpretation is consistent with the principle of spike-timing dependent plasticity (STDP), which may provide the basic mechanism for short term or long term plasticity and be operative in both the adult and neonatal SC. PMID:20016107

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

    PubMed

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

    2013-09-22

    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.

  16. 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

  17. Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor.

    PubMed

    Lu, Ming-Kuei; Chen, Chun-Ming; Duann, Jeng-Ren; Ziemann, Ulf; Chen, Jui-Cheng; Chiou, Shang-Ming; Tsai, Chon-Haw

    2016-01-01

    Parkinson's disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET. PMID:27603204

  18. Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor

    PubMed Central

    Chen, Chun-Ming; Duann, Jeng-Ren; Ziemann, Ulf; Chen, Jui-Cheng; Chiou, Shang-Ming; Tsai, Chon-Haw

    2016-01-01

    Parkinson’s disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET. PMID:27603204

  19. Hippocampal Pathway Plasticity Is Associated with the Ability to Form Novel Memories in Older Adults

    PubMed Central

    Antonenko, Daria; Külzow, Nadine; Cesarz, Magda E.; Schindler, Kristina; Grittner, Ulrike; Flöel, Agnes

    2016-01-01

    White matter deterioration in the aging human brain contributes to cognitive decline. The fornix as main efferent hippocampal pathway is one of the tracts most strongly associated with age-related memory impairment. Its deterioration may predict conversion to Alzheimer’s dementia and its precursors. However, the associations between the ability to form novel memories, fornix microstructure and plasticity in response to training have never been tested. In the present study, 25 healthy older adults (15 women; mean age (SD): 69 (6) years) underwent an object-location training on three consecutive days. Behavioral outcome measures comprised recall performance on the training days, and on 1-day and 1-month follow up assessments. MRI at 3 Tesla was assessed before and after training. Fornix microstructure was determined by fractional anisotropy and mean diffusivity (MD) values from diffusion tensor imaging (DTI). In addition, hippocampal volumes were extracted from high-resolution images; individual hippocampal masks were further aligned to DTI images to determine hippocampal microstructure. Using linear mixed model analysis, we found that the change in fornix FA from pre- to post-training assessment was significantly associated with training success. Neither baseline fornix microstructure nor hippocampal microstructure or volume changes were significantly associated with performance. Further, models including control task performance (auditory verbal learning) and control white matter tract microstructure (uncinate fasciculus and parahippocampal cingulum) did not yield significant associations. Our results confirm that hippocampal pathways respond to short-term cognitive training, and extend previous findings by demonstrating that the magnitude of training-induced structural changes is associated with behavioral success in older adults. This suggests that the amount of fornix plasticity may not only be behaviorally relevant, but also a potential sensitive biomarker

  20. FNIRS-based evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy

    NASA Astrophysics Data System (ADS)

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-03-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2 ± 2.1 years old) with hemiplegic cerebral palsy (CP) was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger tapping task were quantified before, immediately after, and six months after CIMT. Five age-matched healthy children (9.8 ± 1.3 years old) were also imaged at the same time points to provide comparative activation metrics for normal controls. In children with CP the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted six months later. In contrast to this longer term improvement in localized activation response, the laterality index that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed six months later.

  1. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  2. The disorganized visual cortex in reelin-deficient mice is functional and allows for enhanced plasticity.

    PubMed

    Pielecka-Fortuna, Justyna; Wagener, Robin Jan; Martens, Ann-Kristin; Goetze, Bianka; Schmidt, Karl-Friedrich; Staiger, Jochen F; Löwel, Siegrid

    2015-11-01

    A hallmark of neocortical circuits is the segregation of processing streams into six distinct layers. The importance of this layered organization for cortical processing and plasticity is little understood. We investigated the structure, function and plasticity of primary visual cortex (V1) of adult mice deficient for the glycoprotein reelin and their wild-type littermates. In V1 of rl-/- mice, cells with different laminar fates are present at all cortical depths. Surprisingly, the (vertically) disorganized cortex maintains a precise retinotopic (horizontal) organization. Rl-/- mice have normal basic visual capabilities, but are compromised in more challenging perceptual tasks, such as orientation discrimination. Additionally, rl-/- animals learn and memorize a visual task as well as their wild-type littermates. Interestingly, reelin deficiency enhances visual cortical plasticity: juvenile-like ocular dominance plasticity is preserved into late adulthood. The present data offer an important insight into the capabilities of a disorganized cortical system to maintain basic functional properties.

  3. [Malformations of cortical development in adult patients with epilepsy: a series of 79 cases].

    PubMed

    González-Cuevas, Montserrat; Toledo, Manuel; Santamarina, Esteban; Sueiras-Gil, María; Cambrodí-Masip, Roser; Sarria, Silvana; Quintana, Manuel; Alvarez-Sabín, José; Salas-Puig, Javier

    2014-02-16

    Introduccion. Las malformaciones del desarrollo cortical (MDC) son una causa importante de epilepsia, retraso del desarrollo psicomotor o deficits neurologicos. Objetivo. Describir la evolucion clinica a largo plazo y las caracteristicas diferenciales de los distintos grupos de MDC en adultos con epilepsia. Pacientes y metodos. Pacientes mayores de 16 años con MDC confirmada por resonancia magnetica y epilepsia. Se analizaron las caracteristicas de la epilepsia, la presencia de deficits neurologicos, la discapacidad intelectual, los antecedentes de patologia perinatal y el electroencefalograma. Los pacientes se clasificaron en tres grupos (G) segun la clasificacion de Barkovich. Resultados. Se identificaron 85 pacientes con MDC de 2.630 pacientes con epilepsia, y se incluyeron 79 pacientes. Edad media: 37 años, el 57% mujeres. Edad media al inicio de las crisis: 17,8 años. El 59,5% era farmacorresistente. La distribucion de los casos segun la clasificacion de Barkovich fue: G1 (alteraciones de la proliferacion neuronal): 59,5%; G2 (alteraciones de la migracion): 25,3%; y G3 (alteraciones de la organizacion cortical): 15,2%. El 19% presentaba un deficit neurologico focal y el 34,2% tenia un cociente intelectual < 80. Al analizar por grupos, el G3 mostraba un mayor porcentaje de deficits neurologicos focales y discapacidad intelectual que el G1 y el G2 (p < 0,05). Conclusion. Los pacientes con MDC del G3 tienen mayor probabilidad de tener deficit neurologico, discapacidad intelectual y mejor control de las crisis que los pacientes del G1 y G2, que se manifiestan, predominantemente, con epilepsia farmacorresistente.

  4. MuSK levels differ between adult skeletal muscles and influence postsynaptic plasticity.

    PubMed

    Punga, Anna R; Maj, Marcin; Lin, Shuo; Meinen, Sarina; Rüegg, Markus A

    2011-03-01

    Muscle-specific tyrosine kinase (MuSK) is involved in the formation and maintenance of the neuromuscular junction (NMJ), and is necessary for NMJ integrity. As muscle involvement is strikingly selective in pathological conditions in which MuSK is targeted, including congenital myasthenic syndrome with MuSK mutation and MuSK antibody-seropositive myasthenia gravis, we hypothesized that the postsynaptic response to MuSK-agrin signalling differs between adult muscles. Transcript levels of postsynaptic proteins were compared between different muscles in wild-type adult mice. MuSK expression was high in the soleus and sternomastoid muscles and low in the extensor digitorum longus (EDL) and omohyoid muscles. The acetylcholine receptor (AChR) α subunit followed a similar expression pattern, whereas expression of Dok-7, Lrp4 and rapsyn was comparable between the muscles. We subsequently examined muscles in mice that overexpressed a miniaturized form of neural agrin or MuSK. In these transgenic mice, the soleus and sternomastoid muscles responded with formation of ectopic AChR clusters, whereas such clusters were almost absent in the EDL and omohyoid muscles. Electroporation of Dok-7 revealed its important role as an activator of MuSK in AChR cluster formation in adult muscles. Together, our findings indicate for the first time that adult skeletal muscles harbour different endogenous levels of MuSK and that these levels determine the ability to form ectopic AChR clusters upon overexpression of agrin or MuSK. We believe that these findings are important for our understanding of adult muscle plasticity and the selective muscle involvement in neuromuscular disorders in which MuSK is diminished. PMID:21255125

  5. Mechanical loads and cortical bone geometry in healthy children and young adults.

    PubMed

    Wetzsteon, Rachel J; Zemel, Babette S; Shults, Justine; Howard, Krista M; Kibe, Lucy W; Leonard, Mary B

    2011-05-01

    Muscle and bone form a functional unit. While muscle size is a useful surrogate of mechanical load on bone, the independent contributions to bone strength of muscle force, muscle size, gravitational load (body weight), and physical activity have not been assessed. Three hundred twenty-one healthy participants (32% black, 47% male), aged 5-35 years were assessed. Peak dorsiflexion muscle torque (ft-lbs) of the ankle was assessed using isometric dynamometry. Tibia peripheral quantitative computed tomography measures included polar section modulus (Zp; mm(3)), periosteal and endosteal circumference (mm), cortical area (mm(2)), and volumetric bone mineral density (vBMD; mg/cm(3)) at the 38% site, and muscle cross-sectional area (CSA; mm(2)), at the 66% site. Physical activity (average hours per week) was assessed by questionnaire. Log linear regression was used to assess determinants of muscle specific force (MSF; torque relative to muscle CSA) and Zp adjusted for age and tibia length. MSF was greater in blacks than whites (p<0.05) and lower in females than males (p<0.001). Zp was greater in blacks than whites (p=0.002) in Tanner stages 1-4, but the difference was attenuated in Tanner 5 (interaction, p=0.02); R(2)=0.87. Muscle CSA, muscle torque, body weight, and physical activity were added to the model and each load covariate was independently and significantly (all, p<0.02) associated with Zp (R(2)=0.92), periosteal circumference, and cortical area. Inclusion of these measures attenuated but did not eliminate the significant race differences. Only muscle CSA was positively associated with endosteal circumference, while none of the load covariates were associated with vBMD. In conclusion, bone geometry is associated with several factors that define the mechanical load on bone, independent of age, tibia length, maturation, race, and sex. Race differences in Zp were not explained by these measures of mechanical load. Given that inclusion of muscle torque, body weight

  6. Cortical Auditory Evoked Potentials in (Un)aided Normal-Hearing and Hearing-Impaired Adults.

    PubMed

    Van Dun, Bram; Kania, Anna; Dillon, Harvey

    2016-02-01

    Cortical auditory evoked potentials (CAEPs) are influenced by the characteristics of the stimulus, including level and hearing aid gain. Previous studies have measured CAEPs aided and unaided in individuals with normal hearing. There is a significant difference between providing amplification to a person with normal hearing and a person with hearing loss. This study investigated this difference and the effects of stimulus signal-to-noise ratio (SNR) and audibility on the CAEP amplitude in a population with hearing loss. Twelve normal-hearing participants and 12 participants with a hearing loss participated in this study. Three speech sounds-/m/, /g/, and /t/-were presented in the free field. Unaided stimuli were presented at 55, 65, and 75 dB sound pressure level (SPL) and aided stimuli at 55 dB SPL with three different gains in steps of 10 dB. CAEPs were recorded and their amplitudes analyzed. Stimulus SNRs and audibility were determined. No significant effect of stimulus level or hearing aid gain was found in normal hearers. Conversely, a significant effect was found in hearing-impaired individuals. Audibility of the signal, which in some cases is determined by the signal level relative to threshold and in other cases by the SNR, is the dominant factor explaining changes in CAEP amplitude. CAEPs can potentially be used to assess the effects of hearing aid gain in hearing-impaired users. PMID:27587919

  7. Effects of Chronic Heavy Alcohol Consumption and Endurance Exercise on Cancellous and Cortical Bone Microarchitecture in Adult Male Rats

    PubMed Central

    Johnson, Teresa L.; Gaddini, Gino; Branscum, Adam J.; Olson, Dawn A.; Caroline-Westerlind, Kim; Turner, Russell T.; Iwaniec, Urszula T.

    2014-01-01

    Background Bone health is influenced by numerous lifestyle factors, including diet and exercise. Alcohol is a major non-essential constituent of diet and has dose and context-dependent effects on bone. Endurance exercise is associated with increased risk for stress fractures. The purpose of this study was to determine the long-term independent and combined effects of chronic heavy alcohol consumption and endurance exercise (treadmill running) on bone mass and microarchitecture in young adult male Sprague-Dawley rats. Methods Six-month-old male rats were randomized into 4 groups (9–13 rats/group): sedentary+control diet, sedentary+ethanol diet, exercise+control diet, or exercise+ethanol diet. Ethanol-fed rats consumed a liquid diet (ethanol comprised 35% of caloric intake) ad libitum. Control rats were pair-fed the same diet with isocaloric substitution of ethanol with maltose-dextran. Exercise was conducted on a motorized treadmill (15% grade for 30 min) 5 days/week for 16 weeks. Femur and 12th thoracic vertebra were analyzed for bone mineral content (BMC) and density (BMD) using densitometry and cortical and cancellous bone architecture using microcomputed tomography. Results Ethanol consumption resulted in lower femur length, BMC, and BMD, and lower midshaft femur cortical volume, cortical thickness, and polar moment of inertia. In addition, trabecular thickness was lower in vertebra of ethanol-fed rats. Endurance exercise had no independent effect on any endpoints evaluated. A significant interaction between endurance exercise and ethanol was detected for several cancellous endpoints in the distal femur metaphysis. Ethanol-consuming rats that exercised had lower distal femur metaphysis bone volume/tissue volume, trabecular connectivity density, and trabecular thickness compared to exercising rats that consumed control diet. Conclusions The results obtained in this model suggest that chronic heavy alcohol consumption may reduce skeletal integrity by reducing

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

    PubMed

    Jiang, Mingchen C; Elbasiouny, Sherif M; Collins, William F; Heckman, C J

    2015-09-01

    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

  9. Cortical atrophy in young adults with a history of hyperactivity in childhood.

    PubMed

    Nasrallah, H A; Loney, J; Olson, S C; McCalley-Whitters, M; Kramer, J; Jacoby, C G

    1986-03-01

    A computed tomographic (CT) brain scan study was conducted in 24 young males treated and followed up for hyperactivity since childhood. Compared to 27 matched controls, adults with a history of hyperactivity had a significantly greater frequency of cerebral atrophy. No differences in cerebellar atrophy frequency or in lateral cerebral ventricle-to-brain ratio (VBR) were found. The possible associations of hyperactivity or perhaps stimulant drug treatment to atrophic brain changes are discussed.

  10. Postnatal day 7 ethanol treatment causes persistent reductions in adult mouse brain volume and cortical neurons with sex specific effects on neurogenesis.

    PubMed

    Coleman, Leon G; Oguz, Ipek; Lee, Joohwi; Styner, Martin; Crews, Fulton T

    2012-09-01

    Ethanol treatment on postnatal day seven (P7) causes robust brain cell death and is a model of late gestational alcohol exposure (Ikonomidou et al., 2000). To investigate the long-term effects of P7 ethanol treatment on adult brain, mice received either two doses of saline or ethanol on P7 (2.5 g/kg, s.c., 2 h apart) and were assessed as adults (P82) for brain volume (using postmortem MRI) and cellular architecture (using immunohistochemistry). Adult mice that received P7 ethanol had reduced MRI total brain volume (4%) with multiple brain regions being reduced in both males and females. Immunohistochemistry indicated reduced frontal cortical parvalbumin immunoreactive (PV + IR) interneurons (18-33%) and reduced Cux1+IR layer II pyramidal neurons (15%) in both sexes. Interestingly, markers of adult hippocampal neurogenesis differed between sexes, with only ethanol treated males showing increased doublecortin and Ki67 expression (52 and 57% respectively) in the dentate gyrus, consistent with increased neurogenesis compared to controls. These findings suggest that P7 ethanol treatment causes persistent reductions in adult brain volume and frontal cortical neurons in both males and females. Increased adult neurogenesis in males, but not females, is consistent with differential adaptive responses to P7 ethanol toxicity between the sexes. One day of ethanol exposure, e.g. P7, causes persistent adult brain dysmorphology.

  11. Age-related deterioration of cortical responses to slow FM sounds in the auditory belt region of adult C57BL/6 mice.

    PubMed

    Tsukano, Hiroaki; Horie, Masao; Honma, Yuusuke; Ohga, Shinpei; Hishida, Ryuichi; Takebayashi, Hirohide; Takahashi, Sugata; Shibuki, Katsuei

    2013-11-27

    To compare age-related deterioration of neural responses in each subfield of the auditory cortex in C57BL/6 mice, we evaluated amplitudes of tonal responses in young (5-11 weeks old) and adult (16-23 weeks old) groups using transcranial flavoprotein fluorescence imaging. Cortical responses to 20-kHz amplitude-modulated (AM) sounds, which were mainly found in the anterior auditory field (AAF) and the primary auditory cortex (AI) of the core region, were not markedly different between the two groups. In contrast, cortical responses to direction reversal of slow frequency-modulated (FM) sounds, which were mainly found in the ultrasonic field (UF), were significantly disrupted in the adult group compared with those in the young group. To investigate the mechanisms underlying such age-related deterioration, biotinylated dextran amine (BDA) was injected into UF. The number of retrograde labeled neurons in the dorsal division of the medial geniculate body (MGd) was markedly reduced in the adult group compared with that in the young group. These results strongly suggest that cortical responses to FM direction reversal in UF of adult C57BL/6 mice are mainly deteriorated by loss of non-lemniscal thalamic inputs from MGd to UF due to aging.

  12. 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

  13. Small-Angle X-ray Scattering Demonstrates Similar Nanostructure in Cortical Bone from Young Adult Animals of Different Species.

    PubMed

    Kaspersen, Jørn Døvling; Turunen, Mikael Juhani; Mathavan, Neashan; Lages, Sebastian; Pedersen, Jan Skov; Olsson, Ulf; Isaksson, Hanna

    2016-07-01

    Despite the vast amount of studies focusing on bone nanostructure that have been performed for several decades, doubts regarding the detailed structure of the constituting hydroxyapatite crystal still exist. Different experimental techniques report somewhat different sizes and locations, possibly due to different requirements for the sample preparation. In this study, small- and wide-angle X-ray scattering is used to investigate the nanostructure of femur samples from young adult ovine, bovine, porcine, and murine cortical bone, including three different orthogonal directions relative to the long axis of the bone. The radially averaged scattering from all samples reveals a remarkable similarity in the entire q range, which indicates that the nanostructure is essentially the same in all species. Small differences in the data from different directions confirm that the crystals are elongated in the [001] direction and that this direction is parallel to the long axis of the bone. A model consisting of thin plates is successfully employed to describe the scattering and extract the plate thicknesses, which are found to be in the range of 20-40 Å for most samples but 40-60 Å for the cow samples. It is demonstrated that the mineral plates have a large degree of polydispersity in plate thickness. Additionally, and equally importantly, the scattering data and the model are critically evaluated in terms of model uncertainties and overall information content.

  14. Small-Angle X-ray Scattering Demonstrates Similar Nanostructure in Cortical Bone from Young Adult Animals of Different Species.

    PubMed

    Kaspersen, Jørn Døvling; Turunen, Mikael Juhani; Mathavan, Neashan; Lages, Sebastian; Pedersen, Jan Skov; Olsson, Ulf; Isaksson, Hanna

    2016-07-01

    Despite the vast amount of studies focusing on bone nanostructure that have been performed for several decades, doubts regarding the detailed structure of the constituting hydroxyapatite crystal still exist. Different experimental techniques report somewhat different sizes and locations, possibly due to different requirements for the sample preparation. In this study, small- and wide-angle X-ray scattering is used to investigate the nanostructure of femur samples from young adult ovine, bovine, porcine, and murine cortical bone, including three different orthogonal directions relative to the long axis of the bone. The radially averaged scattering from all samples reveals a remarkable similarity in the entire q range, which indicates that the nanostructure is essentially the same in all species. Small differences in the data from different directions confirm that the crystals are elongated in the [001] direction and that this direction is parallel to the long axis of the bone. A model consisting of thin plates is successfully employed to describe the scattering and extract the plate thicknesses, which are found to be in the range of 20-40 Å for most samples but 40-60 Å for the cow samples. It is demonstrated that the mineral plates have a large degree of polydispersity in plate thickness. Additionally, and equally importantly, the scattering data and the model are critically evaluated in terms of model uncertainties and overall information content. PMID:26914607

  15. Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats.

    PubMed

    Abe, Hajime; Saito, Fumiyo; Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) and CNPase(+) and OLIG2(+) oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho(+) oligodendrocytes were detected in the corpus callosum at ≥0.1%. In the dentate gyrus, CPZ at ≥0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1(+) and GRIN2A(+) hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2(+) granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. PMID:26577399

  16. 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.

  17. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    PubMed

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.

  18. Timing of motor cortical stimulation during planar robotic training differentially impacts neuroplasticity in older adults

    PubMed Central

    Massie, Crystal L.; Kantak, Shailesh S.; Narayanan, Priya; Wittenberg, George F.

    2014-01-01

    Objective The objective was to determine how stimulation timing applied during reaching influenced neuroplasticity related to practice. Older adult participants were studied to increase relevance for stroke rehabilitation and aging. Methods Sixteen participants completed 3 sessions of a reaching intervention with 480 planar robotic movement trials. Sub-threshold, single-pulse transcranial magnetic stimulations (TMS) were delivered during the late reaction time (LRT) period, when muscle activity exceeded a threshold (EMG-triggered), or randomly. Assessments included motor evoked potentials (MEP), amplitude, and direction of supra-threshold TMS-evoked movements and were calculated as change scores from baseline. Results The direction of TMS-evoked movements significantly changed after reaching practice (p < 0.05), but was not significantly different between conditions. Movement amplitude changes were significantly different between conditions (p < 0.05), with significant increases following the LRT and random conditions. MEP for elbow extensors and flexors, and the shoulder muscle that opposed the practice movement were significantly different between conditions with positive changes following LRT, negative changes following EMG-triggered, and no changes following the random condition. Motor performance including movement time and peak velocity significantly improved following the training but did not differ between conditions. Conclusions The responsiveness of the motor cortex to stimulation was affected positively by stimulation during the late motor response period and negatively during the early movement period, when stimulation was combined with robotic reach practice. Significance The sensitivity of the activated motor cortex to additional stimulation is highly dynamic. PMID:25283712

  19. Reversibility of developmental heat and cold plasticity is asymmetric and has long-lasting consequences for adult thermal tolerance.

    PubMed

    Slotsbo, Stine; Schou, Mads F; Kristensen, Torsten N; Loeschcke, Volker; Sørensen, Jesper G

    2016-09-01

    The ability of insects to cope with stressful temperatures through adaptive plasticity has allowed them to thrive under a wide range of thermal conditions. Developmental plasticity is generally considered to be a non-reversible phenotypic change, e.g. in morphological traits, while adult acclimation responses are often considered to be reversible physiological responses. However, physiologically mediated thermal acclimation might not follow this general prediction. We investigated the magnitude and rate of reversibility of developmental thermal plasticity responses in heat and cold tolerance of adult flies, using a full factorial design with two developmental and two adult temperatures (15 and 25°C). We show that cold tolerance attained during development is readily adjusted to the prevailing conditions during adult acclimation, with a symmetric rate of decrease or increase. In contrast, heat tolerance is only partly reversible during acclimation and is thus constrained by the temperature during development. The effect of adult acclimation on heat tolerance was asymmetrical, with a general loss of heat tolerance with age. Surprisingly, the decline in adult heat tolerance at 25°C was decelerated in flies developed at low temperatures. This result was supported by correlated responses in two senescence-associated traits and in accordance with a lower rate of ageing after low temperature development, suggesting that physiological age is not reset at eclosion. The results have profound ecological consequences for populations, as optimal developmental temperatures will be dependent on the thermal conditions faced in the adult stage and the age at which they occur. PMID:27353229

  20. 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.

  1. 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

  2. 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. PMID:27375445

  3. Molecular Correlates of Cortical Network Modulation by Long-Term Sensory Experience in the Adult Rat Barrel Cortex

    ERIC Educational Resources Information Center

    Vallès, Astrid; Granic, Ivica; De Weerd, Peter; Martens, Gerard J. M.

    2014-01-01

    Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

  4. Assessments of Muscle Oxygenation and Cortical Activity Using Functional Near-infrared Spectroscopy in Healthy Adults During Hybrid Activation.

    PubMed

    Lin, Tai-You; Wu, Jin-Shang; Lin, Linda L; Ho, Ting-Chuan; Lin, Pei-Yi; Chen, Jia-Jin J

    2016-01-01

    Hybrid activation (HA), patterned electrical stimulation (ES) superimposed on attempted voluntary movement in close synchrony, can augment muscle force output. It has been proposed for limb function restoration and neuromodulation. Limited studies have been performed to investigate the influences of HA on muscle oxygenation and brain cortical activity. The present study investigates muscle oxygenation and cortical activity during isometric knee extension tasks with voluntary contraction (VOL) only, ES only, and with HA at three stimulation intensities, namely 10 mA (HA-I), 30 mA (HA-II), and 50 mA (HA-III). A frequency-domain near-infrared spectroscopy system was employed to assess the muscle oxygenation in the vastus lateralis as well as the cortical activity from the bilateral sensorimotor cortices (SMCs), premotor cortices (PMCs), and supplementary motor areas (SMAs). Our results show that the increased ES contribution during HA significantly increased O2 demand in working muscle, implying that the intervention of ES accelerates the muscle metabolism during muscle contraction. For cortical activation, ES only had a similar cortical activation pattern to that during VOL but with lower activation in SMCs, PMCs, and SMAs. Augmented sensorimotor activation was observed during the HA-II condition. The enhanced level of cortical activation during HA was not only affected by the ES contribution within HA but also related to the functional specificity of cortical areas. Our results suggest that HA can effectively enhance the muscle oxygen demand as well as the activation of cortical regions, and that the ES contribution within HA is a key factor.

  5. Birth Weight and Adult IQ, but Not Anxious-Depressive Psychopathology, Are Associated with Cortical Surface Area: A Study in Twins

    PubMed Central

    Córdova-Palomera, Aldo; Fatjó-Vilas, Mar; Falcón, Carles; Bargalló, Nuria; Alemany, Silvia; Crespo-Facorro, Benedicto; Nenadic, Igor; Fañanás, Lourdes

    2015-01-01

    Background Previous research suggests that low birth weight (BW) induces reduced brain cortical surface area (SA) which would persist until at least early adulthood. Moreover, low BW has been linked to psychiatric disorders such as depression and psychological distress, and to altered neurocognitive profiles. Aims We present novel findings obtained by analysing high-resolution structural MRI scans of 48 twins; specifically, we aimed: i) to test the BW-SA association in a middle-aged adult sample; and ii) to assess whether either depression/anxiety disorders or intellectual quotient (IQ) influence the BW-SA link, using a monozygotic (MZ) twin design to separate environmental and genetic effects. Results Both lower BW and decreased IQ were associated with smaller total and regional cortical SA in adulthood. Within a twin pair, lower BW was related to smaller total cortical and regional SA. In contrast, MZ twin differences in SA were not related to differences in either IQ or depression/anxiety disorders. Conclusion The present study supports findings indicating that i) BW has a long-lasting effect on cortical SA, where some familial and environmental influences alter both foetal growth and brain morphology; ii) uniquely environmental factors affecting BW also alter SA; iii) higher IQ correlates with larger SA; and iv) these effects are not modified by internalizing psychopathology. PMID:26086820

  6. Interhemispheric Plasticity Protects the Deafferented Somatosensory Cortex from Functional Takeover After Nerve Injury

    PubMed Central

    Koretsky, Alan P.

    2014-01-01

    Abstract Functional changes across brain hemispheres have been reported after unilateral cortical or peripheral nerve injury. Interhemispheric callosal connections usually underlie this cortico-cortical plasticity. However, the effect of the altered callosal inputs on local cortical plasticity in the adult brain is not well studied. Ipsilateral functional magnetic resonance imaging (fMRI) activation has been reliably detected in the deafferented barrel cortex (BC) at 2 weeks after unilateral infraorbital denervation (IO) in adult rats. The ipsilateral fMRI signal relies on callosal-mediated interhemispheric plasticity. This form of interhemispheric plasticity provides a good chronic model to study the interaction between callosal inputs and local cortical plasticity. The receptive field of forepaw in the primary somatosensory cortex (S1), which is adjacent to the BC, was mapped with fMRI. The S1 receptive field expanded to take over a portion of the BC in 2 weeks after both ascending inputs and callosal inputs were removed in IO rats with ablated contralateral BC (IO+ablation). This expansion, estimated specifically by fMRI mapping, is significantly larger than what has been observed in the IO rats with intact callosal connectivity, as well as in the rats with sham surgery. This work indicates that altered callosal inputs prevent the functional takeover of the deafferented BC from adjacent cortices and may help preserve the functional identity of the BC. PMID:25117691

  7. Brain cortical thickness and surface area correlates of neurocognitive performance in patients with schizophrenia, bipolar disorder, and healthy adults.

    PubMed

    Hartberg, C B; Sundet, K; Rimol, L M; Haukvik, U K; Lange, E H; Nesvåg, R; Dale, A M; Melle, I; Andreassen, O A; Agartz, I

    2011-11-01

    Relationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology.

  8. 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.

  9. 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.

  10. Phenotypic plasticity in adult life-history strategies compensates for a poor start in life in Trinidadian guppies (Poecilia reticulata).

    PubMed

    Auer, Sonya K

    2010-12-01

    Low food availability during early growth and development can have long-term negative consequences for reproductive success. Phenotypic plasticity in adult life-history decisions may help to mitigate these potential costs, yet adult life-history responses to juvenile food conditions remain largely unexplored. I used a food-manipulation experiment with female Trinidadian guppies (Poecilia reticulata) to examine age-related changes in adult life-history responses to early food conditions, whether these responses varied across different adult food conditions, and how these responses affected overall reproductive success. Guppy females reared on low food as juveniles matured at a later age, at a smaller size, and with less energy reserves than females reared on high food as juveniles. In response to this setback, they changed their investment in growth, reproduction, and fat storage throughout the adult stage such that they were able to catch up in body size, increase their reproductive output, and restore their energy reserves to levels comparable to those of females reared on high food as juveniles. The net effect was that adult female guppies did not merely mitigate but surprisingly were able to fully compensate for the potential long-term negative effects of poor juvenile food conditions on reproductive success.

  11. 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.

  12. 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. PMID:14570544

  13. Blockade of 2-arachidonoylglycerol hydrolysis produces antidepressant-like effects and enhances adult hippocampal neurogenesis and synaptic plasticity.

    PubMed

    Zhang, Zhen; Wang, Wei; Zhong, Peng; Liu, Sarah J; Long, Jonathan Z; Zhao, Li; Gao, Hai-qing; Cravatt, Benjamin F; Liu, Qing-song

    2015-01-01

    The endocannabinoid ligand 2-arachidonoylglycerol (2-AG) is inactivated primarily by monoacylglycerol lipase (MAGL). We have shown recently that chronic treatments with MAGL inhibitor JZL184 produce antidepressant- and anxiolytic-like effects in a chronic unpredictable stress (CUS) model of depression in mice. However, the underlying mechanisms remain poorly understood. Adult hippocampal neurogenesis has been implicated in animal models of anxiety and depression and behavioral effects of antidepressants. We tested whether CUS and chronic JZL184 treatments affected adult neurogenesis and synaptic plasticity in the dentate gyrus (DG) of mouse hippocampus. We report that CUS induced depressive-like behaviors and decreased the number of bromodeoxyuridine-labeled neural progenitor cells and doublecortin-positive immature neurons in the DG, while chronic JZL184 treatments prevented these behavioral and cellular deficits. We also investigated the effects of CUS and chronic JZL184 on a form long-term potentiation (LTP) in the DG known to be neurogenesis-dependent. CUS impaired LTP induction, whereas chronic JZL184 treatments restored LTP in CUS-exposed mice. These results suggest that enhanced adult neurogenesis and long-term synaptic plasticity in the DG of the hippocampus might contribute to antidepressant- and anxiolytic-like behavioral effects of JZL184.

  14. 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

  15. 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.

  16. Adult Thymus Contains FoxN1− Epithelial Stem Cells that Are Bipotent for Medullary and Cortical Thymic Epithelial Lineages

    PubMed Central

    Ucar, Ahmet; Ucar, Olga; Klug, Paula; Matt, Sonja; Brunk, Fabian; Hofmann, Thomas G.; Kyewski, Bruno

    2014-01-01

    Summary Within the thymus, two major thymic epithelial cell (TEC) subsets—cortical and medullary TECs—provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed “thymospheres”). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness. PMID:25148026

  17. Infiltrating cells from host brain restore the microglial population in grafted cortical tissue.

    PubMed

    Wang, Cong; Tao, Sijue; Fang, Yukun; Guo, Jing; Zhu, Lirui; Zhang, Shengxiang

    2016-01-01

    Transplantation of embryonic cortical tissue is considered as a promising therapy for brain injury. Grafted neurons can reestablish neuronal network and improve cortical function of the host brain. Microglia is a key player in regulating neuronal survival and plasticity, but its activation and dynamics in grafted cortical tissue remain unknown. Using two-photon intravital imaging and parabiotic model, here we investigated the proliferation and source of microglia in the donor region by transplanting embryonic cortical tissue into adult cortex. Live imaging showed that the endogenous microglia of the grafted tissue were rapidly lost after transplantation. Instead, host-derived microglia infiltrated and colonized the graft. Parabiotic model suggested that the main source of infiltrating cells is the parenchyma of the host brain. Colonized microglia proliferated and experienced an extensive morphological transition and eventually differentiated into resting ramified morphology. Collectively, these results demonstrated that donor tissue has little contribution to the activated microglia and host brain controls the microglial population in the graft.

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

    PubMed

    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.

  19. Impaired hippocampal plasticity and altered neurogenesis in adult Ube3a maternal deficient mouse model for Angelman syndrome.

    PubMed

    Mardirossian, Sandrine; Rampon, Claire; Salvert, Denise; Fort, Patrice; Sarda, Nicole

    2009-12-01

    Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by mental retardation, seizures and sleep disturbances. It results from lack of the functional maternal allele of UBE3A gene. Ube3a maternal-deficient mice (Ube3a m-/p+), animal models for AS, are impaired in hippocampal-dependent learning tasks as compared with control (Ube3a m+/p+) mice. We first examined the basal expression of immediate early genes which expression is required for synaptic plasticity and memory formation. We found that basal expression of c-fos and Arc genes is reduced in the DG of Ube3a maternal deficient mice compared to their non-transgenic littermates. We then examined whether adult hippocampal neurogenesis, which likely serves as a mechanism toward brain plasticity, is altered in these transgenic mice. Neurogenesis occurs throughout life in mammalian dentate gyrus (DG) and recent findings suggest that newborn granule cells are involved in some forms of learning and memory. Whether maternal Ube3a deletion is detrimental on hippocampal neurogenesis is unclear. Herein, we show, using the mitotic marker Ki67, the birthdating marker 5-bromo-2'-dexoyuridine (BrdU) and the marker doublecortin (DCX) to respectively label cell proliferation, cell survival or young neuron production, that the Ube3a maternal deletion does not affect the proliferation nor the survival of newborn cells in the hippocampus. In contrast, using the postmitotic neuronal marker (NeuN), we show that Ube3a maternal deletion is associated with a lower fraction of BrdU+/NeuN+ newborn neurons among the population of surviving new cells in the hippocampus. Collectively, these findings suggest that some aspects of adult neurogenesis and plasticity are affected by Ube3a deletion and may contribute to the hippocampal dysfunction observed in AS mice.

  20. Distinct Relationships of Intramuscular and Subcutaneous Fat With Cortical Bone: Findings From a Cross-Sectional Study of Young Adult Males and Females

    PubMed Central

    Deere, K.; Sayers, A.; Viljakainen, H. T.; Lawlor, D. A.; Sattar, N.; Kemp, J. P.; Fraser, W. D.

    2013-01-01

    Context: Intracellular fat within muscle and visceral tissue has been suggested to adversely influence bone development. Objective: The aim of the study was to evaluate associations between im fat, as reflected by muscle density as measured by peripheral quantitative computed tomography, and cortical bone parameters in young adults. Design/Setting/Participants: We conducted a cross-sectional analysis of 1703 males and 2243 females aged 17.8 years from the Avon Longitudinal Study of Parents and Children. Outcome Measures: We measured cortical bone parameters from midtibial peripheral quantitative computed tomography scans. Results: Muscle density (inversely related to im fat) was inversely associated with periosteal circumference (PC) (beta = −0.07 [95% confidence interval (CI), −0.1, −0.04]), cortical bone mineral density (BMDC) (beta = −0.21 [95% CI, −0.26, −0.17]), and cortical thickness (CT) (beta = −0.37 [95% CI, −0.42, −0.33]) (males and females combined, adjusted for age, height, gender, and muscle cross-sectional area). In contrast, sc fat area was positively associated with PC (beta = 0.10 [95% CI, 0.07, 0.12]), but no association was seen with BMDC or CT. To examine the role of candidate intermediary metabolic pathways, analyses were repeated after adjustment for insulin, C-reactive protein, and β-C-telopeptides of type I collagen. Whereas similar associations were observed after adjustment for insulin and C-reactive protein, the association between muscle density and BMDC was partially attenuated by adjustment for β-C-telopeptides of type I collagen (beta = −0.14 [95% CI, −0.20, −0.08]). Conclusion: Although im and sc fat were both positively associated with cortical bone mass, the nature of these relationships differed in that im fat was predominantly associated with CT and BMDC, whereas sc fat was mainly associated with PC. These relationships were largely independent of candidate metabolic pathways, such as altered bone

  1. Vascular Function, Cerebral Cortical Thickness, and Cognitive Performance in Middle-Aged Hispanic and Non-Hispanic Caucasian Adults

    PubMed Central

    Pasha, Evan; Kaur, Sonya S.; Gonzales, Mitzi M.; Machin, Daniel R.; Kasischke, Kennon; Tanaka, Hirofumi; Haley, Andreana P.

    2015-01-01

    Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health to measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, gender, years of education, and mental status. Arterial stiffness was characterized via β-stiffness index and carotid-femoral pulse-wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics. PMID:25720950

  2. 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…

  3. 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

  4. Information Processing Differences and Similarities in Adults with Dyslexia and Adults with Attention Deficit Hyperactivity Disorder during a Continuous Performance Test: A Study of Cortical Potentials

    ERIC Educational Resources Information Center

    Dhar, Monica; Been, Pieter H.; Minderaa, Ruud B.; Althaus, Monika

    2010-01-01

    Twenty male adults with ADHD, 16 dyslexic adults, 15 comorbid adults, and 16 normal controls were compared on performance and underlying brain responses, during a cued Continuous Performance Test (O-X CPT), with the aim of discovering features of information processing differentiating between the groups. The study evaluated both cue- and…

  5. Age-related changes in the neurophysiology of language in adults: relationship to regional cortical thinning and white matter microstructure.

    PubMed

    Kemmotsu, Nobuko; Girard, Holly M; Kucukboyaci, N Erkut; McEvoy, Linda K; Hagler, Donald J; Dale, Anders M; Halgren, Eric; McDonald, Carrie R

    2012-08-29

    Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18-33 years) and 10 middle-aged (42-64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250 to 350 ms and in left inferior prefrontal cortex from 350 to 450 ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250 and 350 ms, and were associated with left temporal thinning and frontotemporal FA reductions. N400 reductions were not associated with poorer task performance. Rather, increasing age was associated with reduction in the left prefrontal N400, which in turn was also associated with slower response time. These results reveal that changes in the neurophysiology of language occur by middle age and appear to be partially mediated by structural brain loss. These neurophysiological changes may reflect an adaptive process that ensues as communication between left perisylvian regions declines.

  6. Remodeling sensory cortical maps implants specific behavioral memory.

    PubMed

    Bieszczad, K M; Miasnikov, A A; Weinberger, N M

    2013-08-29

    Neural mechanisms underlying the capacity of memory to be rich in sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels the adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66-kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity was consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects' area of expansion and the tone that was strongest in each animal's memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation.

  7. The Effect of Short-Term Auditory Training on Speech in Noise Perception and Cortical Auditory Evoked Potentials in Adults with Cochlear Implants.

    PubMed

    Barlow, Nathan; Purdy, Suzanne C; Sharma, Mridula; Giles, Ellen; Narne, Vijay

    2016-02-01

    This study investigated whether a short intensive psychophysical auditory training program is associated with speech perception benefits and changes in cortical auditory evoked potentials (CAEPs) in adult cochlear implant (CI) users. Ten adult implant recipients trained approximately 7 hours on psychophysical tasks (Gap-in-Noise Detection, Frequency Discrimination, Spectral Rippled Noise [SRN], Iterated Rippled Noise, Temporal Modulation). Speech performance was assessed before and after training using Lexical Neighborhood Test (LNT) words in quiet and in eight-speaker babble. CAEPs evoked by a natural speech stimulus /baba/ with varying syllable stress were assessed pre- and post-training, in quiet and in noise. SRN psychophysical thresholds showed a significant improvement (78% on average) over the training period, but performance on other psychophysical tasks did not change. LNT scores in noise improved significantly post-training by 11% on average compared with three pretraining baseline measures. N1P2 amplitude changed post-training for /baba/ in quiet (p = 0.005, visit 3 pretraining versus visit 4 post-training). CAEP changes did not correlate with behavioral measures. CI recipients' clinical records indicated a plateau in speech perception performance prior to participation in the study. A short period of intensive psychophysical training produced small but significant gains in speech perception in noise and spectral discrimination ability. There remain questions about the most appropriate type of training and the duration or dosage of training that provides the most robust outcomes for adults with CIs. PMID:27587925

  8. Postnatal maternal separation enhances tonic GABA current of cortical layer 5 pyramidal neurons in juvenile rats and promotes genesis of GABAergic neurons in neocortical molecular layer and subventricular zone in adult rats.

    PubMed

    Feng, Mei; Sheng, Guoxia; Li, Zhongxia; Wang, Jiangping; Ren, Keming; Jin, Xiaoming; Jiang, Kewen

    2014-03-01

    Postnatal maternal separation (PMS) has been shown to be associated with an increased vulnerability to psychiatric illnesses in adulthood. However, the underlying neurological mechanisms are not well understood. Here we evaluated its effects on neurogenesis and tonic GABA currents of cortical layer 5 (L5) pyramidal neurons. PMS not only increased cell proliferation in the subventricular zone, cortical layer 1 and hippocampal dentate gyrus in the adult brain, but also promoted the newly generated cells to differentiate into GABAergic neurons, and PMS adult brain maintained higher ratios of GABAergic neurons in the survival of newly generated cells within 5 days immediately post PMS. Additionally, PMS increased the tonic currents at P7-10 and P30-35 in cortical L5 pyramidal cells. Our results suggest that the newly generated GABAergic neurons and the low GABA concentration-activated tonic currents may be involved in the development of psychiatric disorders after PMS.

  9. Relationships between in vivo microdamage and the remarkable regional material and strain heterogeneity of cortical bone of adult deer, elk, sheep and horse calcanei.

    PubMed

    Skedros, John G; Sybrowsky, Christian L; Anderson, Wm Erick; Chow, Frank

    2011-12-01

    Natural loading of the calcanei of deer, elk, sheep and horses produces marked regional differences in prevalent/predominant strain modes: compression in the dorsal cortex, shear in medial-lateral cortices, and tension/shear in the plantar cortex. This consistent non-uniform strain distribution is useful for investigating mechanisms that mediate the development of the remarkable regional material variations of these bones (e.g. collagen orientation, mineralization, remodeling rates and secondary osteon morphotypes, size and population density). Regional differences in strain-mode-specific microdamage prevalence and/or morphology might evoke and sustain the remodeling that produces this material heterogeneity in accordance with local strain characteristics. Adult calcanei from 11 animals of each species (deer, elk, sheep and horses) were transversely sectioned and examined using light and confocal microscopy. With light microscopy, 20 linear microcracks were identified (deer: 10; elk: six; horse: four; sheep: none), and with confocal microscopy substantially more microdamage with typically non-linear morphology was identified (deer: 45; elk: 24; horse: 15; sheep: none). No clear regional patterns of strain-mode-specific microdamage were found in the three species with microdamage. In these species, the highest overall concentrations occurred in the plantar cortex. This might reflect increased susceptibility of microdamage in habitual tension/shear. Absence of detectable microdamage in sheep calcanei may represent the (presumably) relatively greater physical activity of deer, elk and horses. Absence of differences in microdamage prevalence/morphology between dorsal, medial and lateral cortices of these bones, and the general absence of spatial patterns of strain-mode-specific microdamage, might reflect the prior emergence of non-uniform osteon-mediated adaptations that reduce deleterious concentrations of microdamage by the adult stage of bone development.

  10. Notch Is Required in Adult Drosophila Sensory Neurons for Morphological and Functional Plasticity of the Olfactory Circuit

    PubMed Central

    Struhl, Gary

    2015-01-01

    Olfactory receptor neurons (ORNs) convey odor information to the central brain, but like other sensory neurons were thought to play a passive role in memory formation and storage. Here we show that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. Specifically, we show that Notch activity in ORNs is necessary for the odor specific increase in the volume of glomeruli that occurs as a consequence of prolonged odor exposure. Calcium imaging experiments indicate that Notch in ORNs is also required for the chronic odor induced changes in the physiology of ORNs and the ensuing changes in the physiological response of their second order projection neurons (PNs). We further show that Notch in ORNs acts by both canonical cleavage-dependent and non-canonical cleavage-independent pathways. The Notch ligand Delta (Dl) in PNs switches the balance between the pathways. These data define a circuit whereby, in conjunction with odor, N activity in the periphery regulates the activity of neurons in the central brain and Dl in the central brain regulates N activity in the periphery. Our work highlights the importance of experience dependent plasticity at the first olfactory synapse. PMID:26011623

  11. 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

  12. Does phenotypic plasticity for adult size versus food level in Drosophila melanogaster evolve in response to adaptation to different rearing densities?

    PubMed

    Mueller, Laurence D; Cabral, Larry G

    2012-01-01

    Recent studies with Drosophila have suggested that there is extensive genetic variability for phenotypic plasticity of body size versus food level. If true, we expect that the outcome of evolution at very different food levels should yield genotypes whose adult size show different patterns of phenotypic plasticity. We have tested this prediction with six independent populations of Drosophila melanogaster kept at extreme densities for 125 generations. We found that the phenotypic plasticity of body size versus food level is not affected by selection or the presence of competitors of a different genotype. However, we document increasing among population variation in phenotypic plasticity due to random genetic drift. Several reasons are explored to explain these results including the possibility that the use of highly inbred lines to make inferences about the evolution of genetically variable populations may be misleading.

  13. Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats

    PubMed Central

    Wan, Feng; Bai, Hua-Jing; Liu, Jun-Qi; Tian, Mo; Wang, Yong-Xue; Niu, Xin; Si, Yin-Chu

    2016-01-01

    We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). The area density of PCNA-, Vimentin-, and GFAP-positive cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). PCNA-, GFAP-, and Vimentin-positive cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair. PMID:27294116

  14. 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

  15. Deficient plasticity in the hippocampus and the spiral of addiction: focus on adult neurogenesis.

    PubMed

    Canales, Juan J

    2013-01-01

    Addiction is a complex neuropsychiatric disorder which causes disruption at multiple levels, including cognitive, emotional, and behavioral domains. Traditional biological theories of addiction have focused on the mesolimbic dopamine pathway and the nucleus accumbens as anatomical substrates mediating addictive-like behaviors. More recently, we have begun to recognize the engagement and dynamic influence of a much broader circuitry which encompasses the frontal cortex, the amygdala, and the hippocampus. In particular, neurogenesis in the adult hippocampus has become a major focus of attention due to its ability to influence memory, motivation, and affect, all of which are disrupted in addiction. First, I summarize toxicological data that reveal strongly suppressive effects of drug exposure on adult hippocampal neurogenesis. Then, I discuss the impact of deficient neurogenesis on learning and memory function, stress responsiveness and affective behavior, as they relate to addiction. Finally, I examine recent behavioral observations that implicate neurogenesis in the adult hippocampus in the emergence and maintenance of addictive behavior. The evidence reviewed here suggests that deficient neurogenesis is associated with several components of the downward spiraling loop that characterizes addiction, including elevated sensitivity to drug-induced reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a negative affective state, memory impairment, and inflexible behavior. PMID:22976276

  16. Deficient plasticity in the hippocampus and the spiral of addiction: focus on adult neurogenesis.

    PubMed

    Canales, Juan J

    2013-01-01

    Addiction is a complex neuropsychiatric disorder which causes disruption at multiple levels, including cognitive, emotional, and behavioral domains. Traditional biological theories of addiction have focused on the mesolimbic dopamine pathway and the nucleus accumbens as anatomical substrates mediating addictive-like behaviors. More recently, we have begun to recognize the engagement and dynamic influence of a much broader circuitry which encompasses the frontal cortex, the amygdala, and the hippocampus. In particular, neurogenesis in the adult hippocampus has become a major focus of attention due to its ability to influence memory, motivation, and affect, all of which are disrupted in addiction. First, I summarize toxicological data that reveal strongly suppressive effects of drug exposure on adult hippocampal neurogenesis. Then, I discuss the impact of deficient neurogenesis on learning and memory function, stress responsiveness and affective behavior, as they relate to addiction. Finally, I examine recent behavioral observations that implicate neurogenesis in the adult hippocampus in the emergence and maintenance of addictive behavior. The evidence reviewed here suggests that deficient neurogenesis is associated with several components of the downward spiraling loop that characterizes addiction, including elevated sensitivity to drug-induced reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a negative affective state, memory impairment, and inflexible behavior.

  17. Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy.

    PubMed

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R; Clegg, Nancy J; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-04-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity.

  18. Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-04-01

    Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity.

  19. Evaluation of cortical plasticity in children with cerebral palsy undergoing constraint-induced movement therapy based on functional near-infrared spectroscopy

    PubMed Central

    Cao, Jianwei; Khan, Bilal; Hervey, Nathan; Tian, Fenghua; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Roberts, Heather; Tulchin-Francis, Kirsten; Shierk, Angela; Shagman, Laura; MacFarlane, Duncan; Liu, Hanli; Alexandrakis, George

    2015-01-01

    Abstract. Sensorimotor cortex plasticity induced by constraint-induced movement therapy (CIMT) in six children (10.2±2.1 years old) with hemiplegic cerebral palsy was assessed by functional near-infrared spectroscopy (fNIRS). The activation laterality index and time-to-peak/duration during a finger-tapping task and the resting-state functional connectivity were quantified before, immediately after, and 6 months after CIMT. These fNIRS-based metrics were used to help explain changes in clinical scores of manual performance obtained concurrently with imaging time points. Five age-matched healthy children (9.8±1.3 years old) were also imaged to provide comparative activation metrics for normal controls. Interestingly, the activation time-to-peak/duration for all sensorimotor centers displayed significant normalization immediately after CIMT that persisted 6 months later. In contrast to this improved localized activation response, the laterality index and resting-state connectivity metrics that depended on communication between sensorimotor centers improved immediately after CIMT, but relapsed 6 months later. In addition, for the subjects measured in this work, there was either a trade-off between improving unimanual versus bimanual performance when sensorimotor activation patterns normalized after CIMT, or an improvement occurred in both unimanual and bimanual performance but at the cost of very abnormal plastic changes in sensorimotor activity. PMID:25900145

  20. Go/No Go task performance predicts cortical thickness in the caudal inferior frontal gyrus in young adults with and without ADHD.

    PubMed

    Newman, Erik; Jernigan, Terry L; Lisdahl, Krista M; Tamm, Leanne; Tapert, Susan F; Potkin, Steven G; Mathalon, Daniel; Molina, Brooke; Bjork, James; Castellanos, F Xavier; Swanson, James; Kuperman, Joshua M; Bartsch, Hauke; Chen, Chi-Hua; Dale, Anders M; Epstein, Jeffery N; Group, Mta Neuroimaging

    2016-09-01

    Response inhibition deficits are widely believed to be at the core of Attention-Deficit Hyperactivity Disorder (ADHD). Several studies have examined neural architectural correlates of ADHD, but research directly examining structural correlates of response inhibition is lacking. Here we examine the relationship between response inhibition as measured by a Go/No Go task, and cortical surface area and thickness of the caudal inferior frontal gyrus (cIFG), a region implicated in functional imaging studies of response inhibition, in a sample of 114 young adults with and without ADHD diagnosed initially during childhood. We used multiple linear regression models to test the hypothesis that Go/No Go performance would be associated with cIFG surface area or thickness. Results showed that poorer Go/No Go performance was associated with thicker cIFG cortex, and this effect was not mediated by ADHD status or history of substance use. However, independent of Go/No Go performance, persistence of ADHD symptoms and more frequent cannabis use were associated with thinner cIFG. Go/No Go performance was not associated with cortical surface area. The association between poor inhibitory functioning and thicker cIFG suggests that maturation of this region may differ in low performing participants. An independent association of persistent ADHD symptoms and frequent cannabis use with thinner cIFG cortex suggests that distinct neural mechanisms within this region may play a role in inhibitory function, broader ADHD symptomatology, and cannabis use. These results contribute to Research Domain Criteria (RDoC) by revealing novel associations between neural architectural phenotypes and basic neurobehavioral processes measured dimensionally. PMID:26404018

  1. 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

  2. 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

  3. 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

  4. 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. PMID:24993944

  5. 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.

  6. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

    PubMed Central

    Nusslock, Robin; Almeida, Jorge RC; Forbes, Erika E; Versace, Amelia; Frank, Ellen; LaBarbara, Edmund J; Klein, Crystal R; Phillips, Mary L

    2012-01-01

    Objective Bipolar disorder may be characterized by a hypersensitivity to reward-relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward-processing and approach-related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods Twenty-one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card-guessing paradigm designed to examine reward-related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results Region-of-interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right-sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward, relative to healthy controls (p < 0.05, corrected). Wholebrain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left-lateral OFC activity (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward-relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward-related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness. PMID:22548898

  7. 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.

  8. 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.

  9. 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. PMID:23321639

  10. Can short-term oral fine motor training affect precision of task performance and induce cortical plasticity of the jaw muscles?

    PubMed

    Zhang, Hong; Kumar, Abhishek; Kothari, Mohit; Luo, Xiaoping; Trulsson, Mats; Svensson, Krister G; Svensson, Peter

    2016-07-01

    The aim was to test the hypothesis that short-term oral sensorimotor training of the jaw muscles would increase the precision of task performance and induce neuroplastic changes in the corticomotor pathways, related to the masseter muscle. Fifteen healthy volunteers performed six series with ten trials of an oral sensorimotor task. The task was to manipulate and position a spherical chocolate candy in between the anterior teeth and split it into two equal halves. The precision of the task performance was evaluated by comparing the ratio between the two split halves. A series of "hold-and-split" tasks was also performed before and after the training. The hold force and split force along with the electromyographic (EMG) activity of jaw muscles were recorded. Motor-evoked potentials and cortical motor maps of the right masseter muscle were evoked by transcranial magnetic stimulation. There was a significant effect of series on the precision of the task performance during the short-term oral sensorimotor training (P < 0.002). The hold force during the "hold-and-split" task was significantly lower after training than before the short-term training (P = 0.011). However, there was no change in the split force and the EMG activity of the jaw muscles before and after the training. Further, there was a significant increase in the amplitude of the motor-evoked potentials (P < 0.016) and in the motor cortex map areas (P = 0.033), after the short-term oral sensorimotor training. Therefore, short-term oral sensorimotor task training increased the precision of task performance and induced signs of neuroplastic changes in the corticomotor pathways, related to the masseter muscle.

  11. Can short-term oral fine motor training affect precision of task performance and induce cortical plasticity of the jaw muscles?

    PubMed

    Zhang, Hong; Kumar, Abhishek; Kothari, Mohit; Luo, Xiaoping; Trulsson, Mats; Svensson, Krister G; Svensson, Peter

    2016-07-01

    The aim was to test the hypothesis that short-term oral sensorimotor training of the jaw muscles would increase the precision of task performance and induce neuroplastic changes in the corticomotor pathways, related to the masseter muscle. Fifteen healthy volunteers performed six series with ten trials of an oral sensorimotor task. The task was to manipulate and position a spherical chocolate candy in between the anterior teeth and split it into two equal halves. The precision of the task performance was evaluated by comparing the ratio between the two split halves. A series of "hold-and-split" tasks was also performed before and after the training. The hold force and split force along with the electromyographic (EMG) activity of jaw muscles were recorded. Motor-evoked potentials and cortical motor maps of the right masseter muscle were evoked by transcranial magnetic stimulation. There was a significant effect of series on the precision of the task performance during the short-term oral sensorimotor training (P < 0.002). The hold force during the "hold-and-split" task was significantly lower after training than before the short-term training (P = 0.011). However, there was no change in the split force and the EMG activity of the jaw muscles before and after the training. Further, there was a significant increase in the amplitude of the motor-evoked potentials (P < 0.016) and in the motor cortex map areas (P = 0.033), after the short-term oral sensorimotor training. Therefore, short-term oral sensorimotor task training increased the precision of task performance and induced signs of neuroplastic changes in the corticomotor pathways, related to the masseter muscle. PMID:26914481

  12. Effects of alendronate and strontium ranelate on cancellous and cortical bone mass in glucocorticoid-treated adult rats.

    PubMed

    Sun, P; Cai, D H; Li, Q N; Chen, H; Deng, W M; He, L; Yang, L

    2010-06-01

    We studied the effects of alendronate (Aln) and strontium ranelate (SrR) administration on cancellous and cortical bone in glucocorticoid (GC)-treated rats. Thirty-two 3.5-month male Sprague-Dawley rats were randomized into four groups: age-matched normal control (Nrm), methylprednisolone (Met; 5.0 mg/kg/day, sc, for 5 days/week), Met plus Aln orally (1.0 mg/kg/day), and Met plus SrR orally (900 mg/kg/day). The study period was 9 weeks. DXA was used to evaluate the femoral diaphysis and fifth lumbar vertebra (L5). Histomorphometry was performed in the proximal tibial metaphysis and tibial diaphysis. Met significantly decreased body weight and bone mineral density (BMD) compared with Nrm. Aln and SrR significantly increased body weight and BMD compared with Met. SrR resulted in significantly higher BMD than Aln. Met markedly decreased BV/TV, Tb.Th, and Tb.N and increased Tb.Sp compared with Nrm. Aln and SrR showed significantly increased of BV/TV, Tb.Th, and Tb.N and improved bone architecture. Moreover, Met reduced %Ct.Ar, enlarged %Ma.Ar, and decreased bone formation indices in the periosteum as well as increased ES/BS in the endosteum compared with Nrm. Aln significantly decreased endosteal ES/BS compared with Met. SrR significantly increased %Ct.Ar and bone formation indices in the periosteum as well as the endosteum and decreased endosteal ES/BS compared with Met. Furthermore, SrR led to a significantly higher cancellous and endocortical MS/BS and endocortical bone formation compared with Aln. Our findings suggest SrR at a dose of 900 mg/kg has a greater effect than Aln at 1.0 mg/kg, according to BMD and histomorphometric analysis, in preventing GC-induced osteopenia. Therefore, SrR might be applicable as a bone therapeutic agent to treat secondary osteoporosis in the clinic. PMID:20390406

  13. Functional MRI evidence for language plasticity in adult epileptic patients: Preliminary results

    PubMed Central

    Cousin, Emilie; Baciu, Monica; Pichat, Cédric; Kahane, Philippe; Le Bas, Jean-François

    2008-01-01

    The present fMRI study explores the cerebral reorganisation of language in patients with temporal lobe epilepsy, according to the age of seizures onset (early or late) and the hippocampal sclerosis (associated or not). Seven right-handed control volunteers and seven preoperative adult epileptic patients performed a rhyme decision (language condition) and a visual detection (control condition) tasks in visually presented words and unreadable characters, respectively. All patients were left hemisphere dominant for language. Appropriate statistical analyses provided the following preliminary results: (1) patients compared with healthy subjects showed lower degree of hemispheric lateralization with supplementary involvement of the right hemisphere; (2) the degree of hemispheric specialization depends on the considered region; (3) patients with early seizures show signs of temporal and parietal reorganization more frequently than patients with late onset of seizures; (4) patients with early seizures show a tendency for intra-hemispheric frontal reorganisation; (5) associated hippocampal sclerosis facilitates the inter-hemispheric shift of temporal activation. Although our patients were left hemisphere predominant for language, the statistical analyses indicated that the degree of lateralization was significantly lower than in healthy subjects. This result has been considered as the indication of atypical lateralization of language. PMID:18728818

  14. Neurobiological markers of exercise-related brain plasticity in older adults

    PubMed Central

    Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Olson, Erin A.; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A.; Pence, Brandt D.; Cook, Marc D.; Woods, Jeffrey A.; McAuley, Edward; Kramer, Arthur F.

    2012-01-01

    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. PMID:23123199

  15. 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.

  16. Plasticity in the adult oculomotor system: offline consolidation phase gains in saccade sequence learning.

    PubMed

    Meital, Noya; Korinth, Sebastian Peter; Karni, Avi

    2013-08-28

    When do adults gain in learning an oculomotor sequence? Here we show that oculomotor training can result not only in performance gains within the training session, but also induce robust offline gains in both speed and accuracy. Participants were trained and tested over two consecutive days to perform a sequence of successive saccades. Saccades were directed to four target letters, presented simultaneously at fixed positions. A two alternative-forced choice question, after each trial, ensured that all targets were perceived. Eye tracking measures were tested at the beginning and end of the training session as well as at 24 h post-training. Practice resulted in within-session gains in accuracy and a reduction of target fixation duration (although total trial duration remained unchanged). In addition, the total average path length traveled by the eye increased, reflecting a decrease in undershoot saccades. At 24 h post-training, however, additional gains were expressed in both speed and accuracy of performance; the total trial duration as well as the fixation-position-offsets and the number of corrective saccades decreased. The expression of delayed gains indicates offline skill consolidation processes in the eye-movement control system. Our results show that the optimization of some aspect, specifically saccade speed parameters, of oculomotor sequence performance evolves mainly offline, during the post-training consolidation phase, a pattern suggestive of learning in an expert system. PMID:23867864

  17. Impaired gamma-band activity during perceptual organization in adults with autism spectrum disorders: evidence for dysfunctional network activity in frontal-posterior cortices.

    PubMed

    Sun, Limin; Grützner, Christine; Bölte, Sven; Wibral, Michael; Tozman, Tahmine; Schlitt, Sabine; Poustka, Fritz; Singer, Wolf; Freitag, Christine M; Uhlhaas, Peter J

    2012-07-11

    Current theories of the pathophysiology of autism spectrum disorders (ASD) have focused on abnormal temporal coordination of neural activity in cortical circuits as a core impairment of the disorder. In the current study, we examined the possibility that gamma-band activity may be crucially involved in aberrant brain functioning in ASD. Magneto-encephalographic (MEG) data were recorded from 13 adult human participants with ASD and 16 controls during the presentation of Mooney faces. MEG data were analyzed in the 25-150 Hz frequency range and a beamforming approach was used to identify the sources of spectral power. Participants with ASD showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces, while responses to inverted stimuli were in the normal range. Impaired perceptual organization in the ASD group was accompanied by a reduction in both the amplitude and phase locking of gamma-band activity. A beamforming approach identified distinct networks during perceptual organization in controls and participants with ASD. In controls, perceptual organization of Mooney faces involved increased 60-120 Hz activity in a frontoparietal network, while in the ASD group stronger activation was found in visual regions. These findings highlight the contribution of impaired gamma-band activity toward complex visual processing in ASD, suggesting atypical modulation of high-frequency power in frontoposterior networks.

  18. Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

    PubMed Central

    Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David; Sanberg, Paul R.; Bickford, Paula C.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes. PMID:23301065

  19. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex.

    PubMed

    Jiang, Fang; Stecker, G Christopher; Boynton, Geoffrey M; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness-competition across different cortical areas for functional role. PMID:27458357

  20. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

  1. Imprinting and recalling cortical ensembles.

    PubMed

    Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S; Yuste, Rafael

    2016-08-12

    Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. PMID:27516599

  2. Time in Cortical Circuits

    PubMed Central

    Shadlen, Michael N.; Jazayeri, Mehrdad; Nobre, Anna C.; Buonomano, Dean V.

    2015-01-01

    Time is central to cognition. However, the neural basis for time-dependent cognition remains poorly understood. We explore how the temporal features of neural activity in cortical circuits and their capacity for plasticity can contribute to time-dependent cognition over short time scales. This neural activity is linked to cognition that operates in the present or anticipates events or stimuli in the near future. We focus on deliberation and planning in the context of decision making as a cognitive process that integrates information across time. We progress to consider how temporal expectations of the future modulate perception. We propose that understanding the neural basis for how the brain tells time and operates in time will be necessary to develop general models of cognition. SIGNIFICANCE STATEMENT Time is central to cognition. However, the neural basis for time-dependent cognition remains poorly understood. We explore how the temporal features of neural activity in cortical circuits and their capacity for plasticity can contribute to time-dependent cognition over short time scales. We propose that understanding the neural basis for how the brain tells time and operates in time will be necessary to develop general models of cognition. PMID:26468192

  3. Cortical thinning in psychopathy

    PubMed Central

    Ly, Martina; Motzkin, Julian C.; Philippi, Carissa L.; Kirk, Gregory R.; Newman, Joseph P.; Kiehl, Kent A.; Koenigs, Michael

    2013-01-01

    Objective Psychopathy is a personality disorder associated with severely antisocial behavior and a host of cognitive and affective deficits. The neuropathological basis of the disorder has not been clearly established. Cortical thickness is a sensitive measure of brain structure that has been used to identify neurobiological abnormalities in a number of psychiatric disorders. The purpose of this study is to evaluate cortical thickness and corresponding functional connectivity in criminal psychopaths. Method Using T1 MRI data, we computed cortical thickness maps in a sample of adult male prison inmates selected based on psychopathy diagnosis (n=21 psychopathic inmates, n=31 non-psychopathic inmates). Using rest-fMRI data from a subset of these inmates (n=20 psychopathic inmates, n=20 non-psychopathic inmates), we then computed functional connectivity within networks exhibiting significant thinning among psychopaths. Results Relative to non-psychopaths, psychopaths exhibited significantly thinner cortex in a number of regions, including left insula and dorsal anterior cingulate cortex, bilateral precentral gyrus, bilateral anterior temporal cortex, and right inferior frontal gyrus. These neurostructural differences were not due to differences in age, IQ, or substance abuse. Psychopaths also exhibited a corresponding reduction in functional connectivity between left insula and left dorsal anterior cingulate cortex. Conclusions Psychopathy is associated with a distinct pattern of cortical thinning and reduced functional connectivity. PMID:22581200

  4. Plastic and stable electrophysiological properties of adult avian forebrain song-control neurons across changing breeding conditions.

    PubMed

    Meitzen, John; Weaver, Adam L; Brenowitz, Eliot A; Perkel, David J

    2009-05-20

    Steroid sex hormones drive changes in the nervous system and behavior in many animal taxa, but integrating the former with the latter remains challenging. One useful model system for meeting this challenge is seasonally breeding songbirds. In these species, plasma testosterone levels rise and fall across the seasons, altering song behavior and causing dramatic growth and regression of the song-control system, a discrete set of nuclei that control song behavior. Whereas the cellular mechanisms underlying changes in nucleus volume have been studied as a model for neural growth and degeneration, it is unknown whether these changes in neural structure are accompanied by changes in electrophysiological properties other than spontaneous firing rate. Here we test the hypothesis that passive and active neuronal properties in the forebrain song-control nuclei HVC and RA change across breeding conditions. We exposed adult male Gambel's white-crowned sparrows to either short-day photoperiod or long-day photoperiod and systemic testosterone to simulate nonbreeding and breeding conditions, respectively. We made whole-cell recordings from RA and HVC neurons in acute brain slices. We found that RA projection neuron membrane time constant, capacitance, and evoked and spontaneous firing rates were all increased in the breeding condition; the measured electrophysiological properties of HVC interneurons and projection neurons were stable across breeding conditions. This combination of plastic and stable intrinsic properties could directly impact the song-control system's motor control across seasons, underlying changes in song stereotypy. These results provide a valuable framework for integrating how steroid hormones modulate cellular physiology to change behavior.

  5. Plastic and stable electrophysiological properties of adult avian forebrain song-control neurons across changing breeding conditions.

    PubMed

    Meitzen, John; Weaver, Adam L; Brenowitz, Eliot A; Perkel, David J

    2009-05-20

    Steroid sex hormones drive changes in the nervous system and behavior in many animal taxa, but integrating the former with the latter remains challenging. One useful model system for meeting this challenge is seasonally breeding songbirds. In these species, plasma testosterone levels rise and fall across the seasons, altering song behavior and causing dramatic growth and regression of the song-control system, a discrete set of nuclei that control song behavior. Whereas the cellular mechanisms underlying changes in nucleus volume have been studied as a model for neural growth and degeneration, it is unknown whether these changes in neural structure are accompanied by changes in electrophysiological properties other than spontaneous firing rate. Here we test the hypothesis that passive and active neuronal properties in the forebrain song-control nuclei HVC and RA change across breeding conditions. We exposed adult male Gambel's white-crowned sparrows to either short-day photoperiod or long-day photoperiod and systemic testosterone to simulate nonbreeding and breeding conditions, respectively. We made whole-cell recordings from RA and HVC neurons in acute brain slices. We found that RA projection neuron membrane time constant, capacitance, and evoked and spontaneous firing rates were all increased in the breeding condition; the measured electrophysiological properties of HVC interneurons and projection neurons were stable across breeding conditions. This combination of plastic and stable intrinsic properties could directly impact the song-control system's motor control across seasons, underlying changes in song stereotypy. These results provide a valuable framework for integrating how steroid hormones modulate cellular physiology to change behavior. PMID:19458226

  6. Opioid Receptor-Dependent Sex Differences in Synaptic Plasticity in the Hippocampal Mossy Fiber Pathway of the Adult Rat

    PubMed Central

    Harte-Hargrove, Lauren C.; Varga-Wesson, Ada; Duffy, Aine M.; Milner, Teresa A.

    2015-01-01

    The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus. PMID:25632146

  7. Associative Hebbian Synaptic Plasticity in Primate Visual Cortex

    PubMed Central

    Huang, Shiyong; Rozas, Carlos; Treviño, Mario; Contreras, Jessica; Yang, Sunggu; Song, Lihua; Yoshioka, Takashi; Lee, Hey-Kyoung

    2014-01-01

    In primates, the functional connectivity of adult primary visual cortex is susceptible to be modified by sensory training during perceptual learning. It is widely held that this type of neural plasticity might involve mechanisms like long-term potentiation (LTP) and long-term depression (LTD). NMDAR-dependent forms of LTP and LTD are particularly attractive because in rodents they can be induced in a Hebbian manner by near coincidental presynaptic and postsynaptic firing, in a paradigm termed spike timing-dependent plasticity (STDP). These fundamental properties of LTP and LTD, Hebbian induction and NMDAR dependence, have not been examined in primate cortex. Here we demonstrate these properties in the primary visual cortex of the rhesus macaque (Macaca mulatta), and also show that, like in rodents, STDP is gated by neuromodulators. These findings indicate that the cellular principles governing cortical plasticity are conserved across mammalian species, further validating the use of rodents as a model system. PMID:24872561

  8. Anthropogenic host plant expansion leads a nettle-feeding butterfly out of the forest: consequences for larval survival and developmental plasticity in adult morphology

    PubMed Central

    Merckx, Thomas; Serruys, Mélanie; Van Dyck, Hans

    2015-01-01

    Recent anthropogenic eutrophication has meant that host plants of nettle-feeding insects became quasi-omnipresent in fertile regions of Western Europe. However, host plant resource quality – in terms of microclimate and nutritional value – may vary considerably between the ‘original’ forest habitat and ‘recent’ agricultural habitat. Here, we compared development in both environmental settings using a split-brood design, so as to explore to what extent larval survival and adult morphology in the nettle-feeding butterfly Aglais urticae are influenced by the anthropogenic environment. Nettles along field margins had higher C/N ratios and provided warmer microclimates to larvae. Larvae developed 20% faster and tended to improve their survival rates, on the agricultural land compared to woodland. Our split-brood approach indicated plastic responses within families, but also family effects in the phenotypic responses. Adult males and females had darker wing pigmentation in the drier and warmer agricultural environment, which contrasts with the thermal melanism hypothesis. Developmental plasticity in response to this microclimatically different and more variable habitat was associated with a broader phenotypic parameter space for the species. Both habitat expansion and developmental plasticity are likely contributors to the ecological and evolutionary success of these nettle-feeding insects in anthropogenic environments under high nitrogen load. PMID:25926881

  9. Anthropogenic host plant expansion leads a nettle-feeding butterfly out of the forest: consequences for larval survival and developmental plasticity in adult morphology.

    PubMed

    Merckx, Thomas; Serruys, Mélanie; Van Dyck, Hans

    2015-04-01

    Recent anthropogenic eutrophication has meant that host plants of nettle-feeding insects became quasi-omnipresent in fertile regions of Western Europe. However, host plant resource quality - in terms of microclimate and nutritional value - may vary considerably between the 'original' forest habitat and 'recent' agricultural habitat. Here, we compared development in both environmental settings using a split-brood design, so as to explore to what extent larval survival and adult morphology in the nettle-feeding butterfly Aglais urticae are influenced by the anthropogenic environment. Nettles along field margins had higher C/N ratios and provided warmer microclimates to larvae. Larvae developed 20% faster and tended to improve their survival rates, on the agricultural land compared to woodland. Our split-brood approach indicated plastic responses within families, but also family effects in the phenotypic responses. Adult males and females had darker wing pigmentation in the drier and warmer agricultural environment, which contrasts with the thermal melanism hypothesis. Developmental plasticity in response to this microclimatically different and more variable habitat was associated with a broader phenotypic parameter space for the species. Both habitat expansion and developmental plasticity are likely contributors to the ecological and evolutionary success of these nettle-feeding insects in anthropogenic environments under high nitrogen load. PMID:25926881

  10. Ratio between mature and immature enzymatic cross-links correlates with post-yield cortical bone behavior: An insight into greenstick fractures of the child fibula.

    PubMed

    Berteau, Jean-Philippe; Gineyts, Evelyne; Pithioux, Martine; Baron, Cécile; Boivin, Georges; Lasaygues, Philippe; Chabrand, Patrick; Follet, Hélène

    2015-10-01

    As a determinant of skeletal fragility, the organic matrix is responsible for the post-yield and creep behavior of bone and for its toughness, while the mineral apatite acts on stiffness. Specific to the fibula and ulna in children, greenstick fractures show a plastic in vivo mechanical behavior before bone fracture. During growth, the immature form of collagen enzymatic cross-links gradually decreases, to be replaced by the mature form until adolescence, subsequently remaining constant throughout adult life. However, the link between the cortical bone organic matrix and greenstick fractures in children remains to be explored. Here, we sought to determine: 1) whether plastic bending fractures can occur in vitro, by testing cortical bone samples from children's fibula and 2) whether the post-yield behavior (ωp plastic energy) of cortical bone before fracture is related to total quantity of the collagen matrix, or to the quantity of mature and immature enzymatic cross-links and the quantity of non-enzymatic cross-links. We used a two-step approach; first, a 3-point microbending device tested 22 fibula machined bone samples from 7 children and 3 elderly adults until fracture. Second, biochemical analysis by HPLC was performed on the sample fragments. When pooling two groups of donors, children and elderly adults, results show a rank correlation between total energy dissipated before fracture and age and a linear correlation between plastic energy dissipated before fracture and ratio of immature/mature cross-links. A collagen matrix with more immature cross-links (i.e. a higher immature/mature cross-link ratio) is more likely to plastically deform before fracture. We conclude that this ratio in the sub-nanostructure of the organic matrix in cortical bone from the fibula may go some way towards explaining the variance in post-yield behavior. From a clinical point of view, therefore, our results provide a potential explanation of the presence of greenstick fractures in

  11. Cortical network reorganization guided by sensory input features.

    PubMed

    Kilgard, Michael P; Pandya, Pritesh K; Engineer, Navzer D; Moucha, Raluca

    2002-12-01

    Sensory experience alters the functional organization of cortical networks. Previous studies using behavioral training motivated by aversive or rewarding stimuli have demonstrated that cortical plasticity is specific to salient inputs in the sensory environment. Sensory experience associated with electrical activation of the basal forebrain (BasF) generates similar input specific plasticity. By directly engaging plasticity mechanisms and avoiding extensive behavioral training, BasF stimulation makes it possible to efficiently explore how specific sensory features contribute to cortical plasticity. This review summarizes our observations that cortical networks employ a variety of strategies to improve the representation of the sensory environment. Different combinations of receptive-field, temporal, and spectrotemporal plasticity were generated in primary auditory cortex neurons depending on the pitch, modulation rate, and order of sounds paired with BasF stimulation. Simple tones led to map expansion, while modulated tones altered the maximum cortical following rate. Exposure to complex acoustic sequences led to the development of combination-sensitive responses. This remodeling of cortical response characteristics may reflect changes in intrinsic cellular mechanisms, synaptic efficacy, and local neuronal connectivity. The intricate relationship between the pattern of sensory activation and cortical plasticity suggests that network-level rules alter the functional organization of the cortex to generate the most behaviorally useful representation of the sensory environment.

  12. Auditory cortical detection and discrimination correlates with communicative significance.

    PubMed

    Liu, Robert C; Schreiner, Christoph E

    2007-07-01

    Plasticity studies suggest that behavioral relevance can change the cortical processing of trained or conditioned sensory stimuli. However, whether this occurs in the context of natural communication, where stimulus significance is acquired through social interaction, has not been well investigated, perhaps because neural responses to species-specific vocalizations can be difficult to interpret within a systematic framework. The ultrasonic communication system between isolated mouse pups and adult females that either do or do not recognize the calls' significance provides an opportunity to explore this issue. We applied an information-based analysis to multi- and single unit data collected from anesthetized mothers and pup-naïve females to quantify how the communicative significance of pup calls affects their encoding in the auditory cortex. The timing and magnitude of information that cortical responses convey (at a 2-ms resolution) for pup call detection and discrimination was significantly improved in mothers compared to naïve females, most likely because of changes in call frequency encoding. This was not the case for a non-natural sound ensemble outside the mouse vocalization repertoire. The results demonstrate that a sensory cortical change in the timing code for communication sounds is correlated with the vocalizations' behavioral relevance, potentially enhancing functional processing by improving its signal to noise ratio. PMID:17564499

  13. Input-increase and input-decrease types of cortical reorganization after upper extremity amputation in humans.

    PubMed

    Elbert, T; Sterr, A; Flor, H; Rockstroh, B; Knecht, S; Pantev, C; Wienbruch, C; Taub, E

    1997-10-01

    A plastic remodeling of regions in somatosensory cortex has previously been observed to occur in separate experimental paradigms in response to loss of somatosensory input and to increase in input. In this study, both types of cortical reorganization have been observed to occur concurrently in the same adult human nervous system as a result of a single intervention. Following upper extremity amputation, magnetic source imaging revealed that tactile stimulation of the lip evoked responses not only in the area of the somatosensory cortex corresponding to the face, but also within the cortical region that would normally correspond to the now absent hand. This "invasion" of the cortical amputation zone was accompanied by a significant increase in the size of the representation of the digits of the intact hand, presumably as a result of an increased importance of sensory stimulation consequent to increased dependence on that hand imposed by the loss of the contralateral extremity.

  14. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex.

    PubMed

    Beurdeley, Marine; Spatazza, Julien; Lee, Henry H C; Sugiyama, Sayaka; Bernard, Clémence; Di Nardo, Ariel A; Hensch, Takao K; Prochiantz, Alain

    2012-07-01

    Specific transfer of (orthodenticle homeobox 2) Otx2 homeoprotein into GABAergic interneurons expressing parvalbumin (PV) is necessary and sufficient to open, then close, a critical period (CP) of plasticity in the developing mouse visual cortex. The accumulation of endogenous Otx2 in PV cells suggests the presence of specific Otx2 binding sites. Here, we find that perineuronal nets (PNNs) on the surfaces of PV cells permit the specific, constitutive capture of Otx2. We identify a 15 aa domain containing an arginine-lysine doublet (RK peptide) within Otx2, bearing prototypic traits of a glycosaminoglycan (GAG) binding sequence that mediates Otx2 binding to PNNs, and specifically to chondroitin sulfate D and E, with high affinity. Accordingly, PNN hydrolysis by chondroitinase ABC reduces the amount of endogenous Otx2 in PV cells. Direct infusion of RK peptide similarly disrupts endogenous Otx2 localization to PV cells, reduces PV and PNN expression, and reopens plasticity in adult mice. The closure of one eye during this transient window reduces cortical acuity and is specific to the RK motif, as an Alanine-Alanine variant or a scrambled peptide fails to reactivate plasticity. Conversely, this transient reopening of plasticity in the adult restores binocular vision in amblyopic mice. Thus, one function of PNNs is to facilitate the persistent internalization of Otx2 by PV cells to maintain CP closure. The pharmacological use of the Otx2 GAG binding domain offers a novel, potent therapeutic tool with which to restore cortical plasticity in the mature brain. PMID:22764251

  15. Neutralization of Nogo-A Enhances Synaptic Plasticity in the Rodent Motor Cortex and Improves Motor Learning in Vivo

    PubMed Central

    Weinmann, Oliver; Kellner, Yves; Yu, Xinzhu; Vicente, Raul; Gullo, Miriam; Kasper, Hansjörg; Lussi, Karin; Ristic, Zorica; Luft, Andreas R.; Rioult-Pedotti, Mengia; Zuo, Yi; Zagrebelsky, Marta; Schwab, Martin E.

    2014-01-01

    The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex. PMID:24966370

  16. Cortical Plasticity Associated with Stuttering Therapy

    ERIC Educational Resources Information Center

    Neumann, Katrin; Preibisch, Christine; Euler, Harald A.; von Gudenberg, Alexander Wolff; Lanfermann, Heinrich; Gall, Volker; Giraud, Anne-Lise

    2005-01-01

    Neuroimaging studies have indicated that persistent developmental stuttering (PDS) may be associated both with an abnormality in white matter of left-hemispheric speech areas and a right-hemispheric hyperactivity. The latter may compensate for the deficient structural connectivity in the left hemisphere. To investigate the effects of stuttering…

  17. Chronic stress, cortical plasticity and neuroecology.

    PubMed

    Reser, Jared Edward

    2016-08-01

    Prolonged psychological stress and accompanying elevations in blood cortisol are known to induce hypometabolism and decreasing synaptic density in the hippocampus and the prefrontal cortex (PFC). This article evaluates and explores evidence supporting the hypothesis that these, and other, selective effects of prolonged stress constitute a neuroecological program that adaptively modifies behavior in mammals experiencing adverse conditions. Three complementary hypotheses are proposed: (1) chronic stress signifies that the prevailing environment is life-threatening, indicating that the animal should decrease activity in brain areas capable of inhibiting the stress axis; (2) stress signifies that the environment is unpredictable, that high-level cognition may be less effective, and that the animal should increase its reliance on defensive, procedural and instinctual behaviors mediated by lower brain centers; and (3) stress indicates that environmental events are proving difficult to systemize based on delayed associations, and thus the maintenance of contextual, task-relevant information in the PFC need not be maintained for temporally-extended periods. Humans, along with countless other species of vertebrates, have been shown to make predictive, adaptive responses to chronic stress in many systems including metabolic, cardiovascular, neuroendocrine, and even amygdalar and striatal systems. It is proposed in this article that humans and other mammals may also have an inducible, cerebrocortical response to pronounced stress that mediates a transition from time-intensive, explicit (controlled/attentional/top-down) processing of information to quick, implicit (automatic/preattentive/bottom-up) processing. PMID:27334119

  18. Sleep and developmental plasticity not just for kids.

    PubMed

    Frank, Marcos Gabriel

    2011-01-01

    In a variety of mammalian species, sleep amounts are highest during developmental periods of rapid brain development and synaptic plasticity than at any other time in life [Frank, M. G. & Heller, H. C. (1997a). Development of REM and slow wave sleep in the rat. American Journal of Physiology, 272, R1792-R1799; Jouvet-Mounier, D., Astic, L., & Lacote, D. (1970). Ontogenesis of the states of sleep in rat, cat and guinea pig during the first postnatal month. Developmental Psychobiology, 2, 216-239; Roffwarg, H. P., Muzio, J. N., & Dement, W. C. (1966). Ontogenetic development of the human sleep-dream cycle. Science, 604-619]. Many of the mechanisms governing developmental plasticity also mediate plasticity in the adult brain. Therefore, studying the role of sleep in developmental plasticity may provide insights more generally into sleep function across the lifespan. In this chapter, I review the evidence that supports a critical role for sleep in developmental brain plasticity. I begin with an overview of past studies that support a role for sleep in general brain maturation. This is followed by more recent findings in the developing visual cortex that more specifically address a possible role for sleep in cortical plasticity. PMID:21854965

  19. Sleep and developmental plasticity not just for kids.

    PubMed

    Frank, Marcos Gabriel

    2011-01-01

    In a variety of mammalian species, sleep amounts are highest during developmental periods of rapid brain development and synaptic plasticity than at any other time in life [Frank, M. G. & Heller, H. C. (1997a). Development of REM and slow wave sleep in the rat. American Journal of Physiology, 272, R1792-R1799; Jouvet-Mounier, D., Astic, L., & Lacote, D. (1970). Ontogenesis of the states of sleep in rat, cat and guinea pig during the first postnatal month. Developmental Psychobiology, 2, 216-239; Roffwarg, H. P., Muzio, J. N., & Dement, W. C. (1966). Ontogenetic development of the human sleep-dream cycle. Science, 604-619]. Many of the mechanisms governing developmental plasticity also mediate plasticity in the adult brain. Therefore, studying the role of sleep in developmental plasticity may provide insights more generally into sleep function across the lifespan. In this chapter, I review the evidence that supports a critical role for sleep in developmental brain plasticity. I begin with an overview of past studies that support a role for sleep in general brain maturation. This is followed by more recent findings in the developing visual cortex that more specifically address a possible role for sleep in cortical plasticity.

  20. Norepinephrine is necessary for experience-dependent plasticity in the developing mouse auditory cortex.

    PubMed

    Shepard, Kathryn N; Liles, L Cameron; Weinshenker, David; Liu, Robert C

    2015-02-11

    Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this window's importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine β-hydroxylase knock-out (Dbh(-/-)) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh(-/-) mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex. PMID:25673838

  1. Inhibition of PI3K-Akt Signaling Blocks Exercise-Mediated Enhancement of Adult Neurogenesis and Synaptic Plasticity in the Dentate Gyrus

    PubMed Central

    Bruel-Jungerman, Elodie; Veyrac, Alexandra; Dufour, Franck; Horwood, Jennifer; Laroche, Serge; Davis, Sabrina

    2009-01-01

    Background Physical exercise has been shown to increase adult neurogenesis in the dentate gyrus and enhances synaptic plasticity. The antiapoptotic kinase, Akt has also been shown to be phosphorylated following voluntary exercise; however, it remains unknown whether the PI3K-Akt signaling pathway is involved in exercise-induced neurogenesis and the associated facilitation of synaptic plasticity in the dentate gyrus. Methodology/Principal Findings To gain insight into the potential role of this signaling pathway in exercise-induced neurogenesis and LTP in the dentate gyrus rats were infused with the PI3K inhibitor, LY294002 or vehicle control solution (icv) via osmotic minipumps and exercised in a running wheel for 10 days. Newborn cells in the dentate gyrus were date-labelled with BrdU on the last 3 days of exercise. Then, they were either returned to the home cage for 2 weeks to assess exercise-induced LTP and neurogenesis in the dentate gyrus, or were killed on the last day of exercise to assess proliferation and activation of the PI3K-Akt cascade using western blotting. Conclusions/Significance Exercise increases cell proliferation and promotes survival of adult-born neurons in the dentate gyrus. Immediately after exercise, we found that Akt and three downstream targets, BAD, GSK3β and FOXO1 were activated. LY294002 blocked exercise-induced phosphorylation of Akt and downstream target proteins. This had no effect on exercise-induced cell proliferation, but it abolished most of the beneficial effect of exercise on the survival of newly generated dentate gyrus neurons and prevented exercise-induced increase in dentate gyrus LTP. These results suggest that activation of the PI3 kinase-Akt signaling pathway plays a significant role via an antiapoptotic function in promoting survival of newly formed granule cells generated during exercise and the associated increase in synaptic plasticity in the dentate gyrus. PMID:19936256

  2. A Sensitive Period for Language in the Visual Cortex: Distinct Patterns of Plasticity in Congenitally versus Late Blind Adults

    ERIC Educational Resources Information Center

    Bedny, Marina; Pascual-Leone, Alvaro; Dravida, Swethasri; Saxe, Rebecca

    2012-01-01

    Recent evidence suggests that blindness enables visual circuits to contribute to language processing. We examined whether this dramatic functional plasticity has a sensitive period. BOLD fMRI signal was measured in congenitally blind, late blind (blindness onset 9-years-old or later) and sighted participants while they performed a sentence…

  3. Long-term plasticity in adult somatosensory cortex: functional reorganization after surgical removal of an arteriovenous malformation.

    PubMed

    Burianová, Hana; Rich, Anina N; Williams, Mark; Morgan, Michael; Marstaller, Lars; Maruff, Paul; Baker, Chris I; Savage, Greg

    2015-01-01

    The temporal scale of neuroplasticity following acute alterations in brain structure due to neurosurgical intervention is still under debate. We conducted a longitudinal study with the objective of investigating the postoperative changes in a patient who underwent cerebrovascular surgery and who subsequently lost proprioception in the fingers of her right hand. The results show increased activation in contralesional somatosensory areas, additional recruitment of premotor and posterior parietal areas, and changes in functional connectivity with left postcentral gyrus. These findings demonstrate long-term modifications of cortical organization and as such have important implications for treatment strategies for patients with brain injury. PMID:25265167

  4. Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.

    PubMed

    Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M; Löwel, Siegrid

    2016-01-01

    Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of

  5. Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.

    PubMed

    Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M; Löwel, Siegrid

    2016-01-01

    Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of

  6. Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice

    PubMed Central

    Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M.; Löwel, Siegrid

    2016-01-01

    Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of

  7. Network Plasticity as Bayesian Inference

    PubMed Central

    Legenstein, Robert; Maass, Wolfgang

    2015-01-01

    General results from statistical learning theory suggest to understand not only brain computations, but also brain plasticity as probabilistic inference. But a model for that has been missing. We propose that inherently stochastic features of synaptic plasticity and spine motility enable cortical networks of neurons to carry out probabilistic inference by sampling from a posterior distribution of network configurations. This model provides a viable alternative to existing models that propose convergence of parameters to maximum likelihood values. It explains how priors on weight distributions and connection probabilities can be merged optimally with learned experience, how cortical networks can generalize learned information so well to novel experiences, and how they can compensate continuously for unforeseen disturbances of the network. The resulting new theory of network plasticity explains from a functional perspective a number of experimental data on stochastic aspects of synaptic plasticity that previously appeared to be quite puzzling. PMID:26545099

  8. A sensitive period for language in the visual cortex: Distinct patterns of plasticity in congenitally versus late blind adults

    PubMed Central

    Bedny, Marina; Pascual-Leone, Alvaro; Dravida, Swethasri; Saxe, Rebecca

    2012-01-01

    Recent evidence suggests that blindness enables visual circuits to contribute to language processing. We examined whether this dramatic functional plasticity has a sensitive period. BOLD fMRI signal was measured in congenitally blind, late blind (blindness onset 9-years-old or later) and sighted participants while they performed a sentence comprehension task. In a control condition, participants listened to backwards speech and made match/non-match to sample judgments. In both, congenitally and late blind participants BOLD signal increased in bilateral foveal-pericalcarine cortex during response preparation, irrespective of whether the stimulus was a sentence or backwards speech. However, only in congenitally blind people left occipital areas (pericalcarine, extrastriate, fusiform and lateral) responded more to sentences than backwards speech. We conclude that age of blindness onset constrains the non-visual functions of occipital cortex: while plasticity is present in both congenitally and late blind individuals, recruitment of visual circuits for language depends on blindness during childhood. PMID:22154509

  9. Variability in action: Contributions of a songbird cortical-basal ganglia circuit to vocal motor learning and control.

    PubMed

    Woolley, S C; Kao, M H

    2015-06-18

    Many motor behaviors, from walking to speaking, are acquired through experience, in particular, through trial-and-error learning. The acquisition and maintenance of such motor behaviors in a wide range of species, including humans, appear to depend on cortical-basal ganglia circuits. In this review, we discuss recent studies in songbirds that have been pivotal in informing our current understanding of motor learning and cortical-basal ganglia function. Songbirds are important ethological model systems for the study of motor learning because young songbirds naturally develop and refine their songs through trial-and-error learning. In addition, reinforcement mechanisms are hypothesized to be important for the maintenance and plasticity of structured adult song. Computational and experimental studies highlight the importance of vocal motor variability as the substrate upon which reinforcement mechanisms could operate to shape developing song and to maintain adult song. Recent studies in songbirds indicate that this vocal motor variability is actively generated and modulated by a highly specialized cortical-basal ganglia circuit evolved for a single behavior, song. We argue that these and other recent findings illustrate how the tight association between a specialized neural circuit and a natural behavior make songbirds a unique and powerful model in which to investigate the neural substrates of motor learning and plasticity.

  10. Infiltrating cells from host brain restore the microglial population in grafted cortical tissue

    PubMed Central

    Wang, Cong; Tao, Sijue; Fang, Yukun; Guo, Jing; Zhu, Lirui; Zhang, Shengxiang

    2016-01-01

    Transplantation of embryonic cortical tissue is considered as a promising therapy for brain injury. Grafted neurons can reestablish neuronal network and improve cortical function of the host brain. Microglia is a key player in regulating neuronal survival and plasticity, but its activation and dynamics in grafted cortical tissue remain unknown. Using two-photon intravital imaging and parabiotic model, here we investigated the proliferation and source of microglia in the donor region by transplanting embryonic cortical tissue into adult cortex. Live imaging showed that the endogenous microglia of the grafted tissue were rapidly lost after transplantation. Instead, host-derived microglia infiltrated and colonized the graft. Parabiotic model suggested that the main source of infiltrating cells is the parenchyma of the host brain. Colonized microglia proliferated and experienced an extensive morphological transition and eventually differentiated into resting ramified morphology. Collectively, these results demonstrated that donor tissue has little contribution to the activated microglia and host brain controls the microglial population in the graft. PMID:27615195

  11. Infiltrating cells from host brain restore the microglial population in grafted cortical tissue.

    PubMed

    Wang, Cong; Tao, Sijue; Fang, Yukun; Guo, Jing; Zhu, Lirui; Zhang, Shengxiang

    2016-01-01

    Transplantation of embryonic cortical tissue is considered as a promising therapy for brain injury. Grafted neurons can reestablish neuronal network and improve cortical function of the host brain. Microglia is a key player in regulating neuronal survival and plasticity, but its activation and dynamics in grafted cortical tissue remain unknown. Using two-photon intravital imaging and parabiotic model, here we investigated the proliferation and source of microglia in the donor region by transplanting embryonic cortical tissue into adult cortex. Live imaging showed that the endogenous microglia of the grafted tissue were rapidly lost after transplantation. Instead, host-derived microglia infiltrated and colonized the graft. Parabiotic model suggested that the main source of infiltrating cells is the parenchyma of the host brain. Colonized microglia proliferated and experienced an extensive morphological transition and eventually differentiated into resting ramified morphology. Collectively, these results demonstrated that donor tissue has little contribution to the activated microglia and host brain controls the microglial population in the graft. PMID:27615195

  12. Mapping of cortical activity in the first two decades of life: a high-density sleep electroencephalogram study.

    PubMed

    Kurth, Salomé; Ringli, Maya; Geiger, Anja; LeBourgeois, Monique; Jenni, Oskar G; Huber, Reto

    2010-10-01

    Evidence that electroencephalography (EEG) slow-wave activity (SWA) (EEG spectral power in the 1-4.5 Hz band) during non-rapid eye movement sleep (NREM) reflects plastic changes is increasing (Tononi and Cirelli, 2006). Regional assessment of gray matter development from neuroimaging studies reveals a posteroanterior trajectory of cortical maturation in the first three decades of life (Shaw et al., 2008). Our aim was to test whether this regional cortical maturation is reflected in regional changes of sleep SWA. We evaluated all-night high-density EEG (128 channels) in 55 healthy human subjects (2.4-19.4 years) and assessed age-related changes in NREM sleep topography. As in adults, we observed frequency-specific topographical distributions of sleep EEG power in all subjects. However, from early childhood to late adolescence, the location on the scalp showing maximal SWA underwent a shift from posterior to anterior regions. This shift along the posteroanterior axis was only present in the SWA frequency range and remained stable across the night. Changes in the topography of SWA during sleep parallel neuroimaging study findings indicating cortical maturation starts early in posterior areas and spreads rostrally over the frontal cortex. Thus, SWA might reflect the underlying processes of cortical maturation. In the future, sleep SWA assessments may be used as a clinical tool to detect aberrations in cortical maturation.

  13. Plastic Surgery

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Plastic Surgery KidsHealth > For Teens > Plastic Surgery Print A ... her forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word " ...

  14. Passive exercise of the hind limbs after complete thoracic transection of the spinal cord promotes cortical reorganization.

    PubMed

    Graziano, Alessandro; Foffani, Guglielmo; Knudsen, Eric B; Shumsky, Jed; Moxon, Karen A

    2013-01-01

    Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain. PMID:23349859

  15. Dissecting natural sensory plasticity: Hormones and experience in a maternal context

    PubMed Central

    Miranda, Jason A.; Liu, Robert C.

    2009-01-01

    There is a growing consensus that the auditory system is dynamic in its representation of behaviorally relevant sounds. The auditory cortex in particular seems to be an important locus for plasticity that may reflect the memory of such sounds, or functionally improve their processing. The mechanisms that underlie these changes may be either intrinsic because they depend on the receiver’s physiological state, or extrinsic because they arise from the context in which behavioral relevance is gained. Research in a mouse model of acoustic communication between offspring and adult females offers the opportunity to explore both of these contributions to auditory cortical plasticity in a natural context. Recent works have found that after the vocalizations of infant mice become behaviorally relevant to mothers, auditory cortical activity is significantly changed in a way that may improve their processing. Here we consider the hypothesis that maternal hormones (intrinsic factor) and sensory experience (extrinsic factor) contribute together to drive these changes, focusing specifically on the evidence that well-known experience-dependent mechanisms of cortical plasticity can be modulated by hormones. PMID:19401225

  16. On the Plasticity of Semantic Generalizations: Children and Adults Modify Their Verb Lexicalization Biases in Response to Changing Input

    ERIC Educational Resources Information Center

    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;…

  17. Cortical reorganization in the aging brain.

    PubMed

    Dinse, Hubert R

    2006-01-01

    Aging exerts major reorganization and remodeling at all levels of brain structure and function. Studies in aged animals and in human elderly individuals demonstrate that sensorimotor cortical representational maps undergo significant alterations. Because cortical reorganization is paralleled by a decline in perceptual and behavioral performance, this type of cortical remodeling differs from the plastic reorganization observed during learning processes in young individuals where map changes are associated with a gain in performance. It is now clear that brain plasticity is operational into old age; therefore, protocols for interventions such as training, exercising, practicing, and stimulation, which make use of neuroplasticity principles, are effective to ameliorate some forms of cortical and behavioral age-related changes, indicating that aging effects are not irreversible but treatable. However, old individuals cannot be rejuvenated, but restoration of function is possible through the emergence of new processing strategies. This implies that cortical reorganization in the aging brain occurs twice: during aging, and during treatment of age-related changes.

  18. Sleep Promotes Cortical Response Potentiation Following Visual Experience

    PubMed Central

    Aton, Sara J.; Suresh, Aneesha; Broussard, Christopher; Frank, Marcos G.

    2014-01-01

    Study Objectives: Sleep has been hypothesized to globally reduce synaptic strength. However, recent findings suggest that in the context of learning and memory consolidation, sleep may promote synaptic potentiation. We tested the requirement for sleep in a naturally occurring form of experience-dependent synaptic potentiation in the adult mouse visual cortex (V1), which is initiated by patterned visual experience. Design: Visual responses were recorded in individual V1 neurons before and after presentation of an oriented grating stimulus, and after subsequent sleep or sleep deprivation. Measurements and Results: We find that V1 response potentiation—associated with a shift in orientation preference in favor of the presented stimulus—occurs only after sleep and only during the entrained circadian sleep phase, and is blocked by sleep deprivation. Induction of plasticity following stimulus presentation is associated with an increase in principal neuron firing in V1, which is present in all behavioral states and occurs regardless of time of day. Sleep dependent potentiation is proportional to phase-locking of neuronal activity with thalamocortical spindle oscillations. Conclusions: Our results suggest that sleep can promote cortical synaptic potentiation in vivo, and that this potentiation may be mediated by slow wave sleep spindles. Citation: Aton SJ, Suresh A, Broussard C, Frank MG. Sleep promotes cortical response potentiation following visual experience. SLEEP 2014;37(7):1163-1170. PMID:25061244

  19. The effect of larval and early adult experience on behavioural plasticity of the aphid parasitoid Aphidius ervi (Hymenoptera, Braconidae, Aphidiinae)

    NASA Astrophysics Data System (ADS)

    Villagra, Cristian A.; Pennacchio, Francesco; Niemeyer, Hermann M.

    2007-11-01

    The relevance of the integration of preimaginal and eclosion experiences on the subsequent habitat preferences and mate finding by the adult has been rarely tested in holometabolous insects. In this work, the effect of larval and early adult experiences on the behavioural responses of adult males of the aphid parasitoid, Aphidius ervi, towards volatiles from the host-plant complex (HPC) and from conspecific females were evaluated. Two experience factors were considered: host diet (normal diet=ND; artificial diet=AD), and eclosion, i.e. extraction or non-extraction of the parasitoid larva from the parasitised aphid (extracted=EX; non-extracted=NE). Thus, four treatments were set up: ND/NE, ND/EX, AD/NE and AD/EX. Glass Y-tube olfactometers were used to investigate the responses of adult A. ervi males to the odour sources used. Males from the ND/NE treatment showed a shorter latency to the first choice of olfactometer arms, displayed a marked preference towards the HPC olfactometer arm, and spent more time in the HPC arm than males from the other treatments. Only the interaction of host diet and eclosion experiences proved to be relevant in explaining the differences in latency to first choice, time spent in olfactometers arms, and behaviours displayed in the olfactometer arms. These results show the importance of the integration of larval and eclosion experiences in the development of stereotyped responses of the adults. This process may involve memory retention from the preimaginal and emergence period, but further research is needed to disentangle the contribution of each stage. The response to conspecific females was much less affected by the treatments in relation to first arm choice and times in olfactometer arms, suggesting a pheromone-mediated behaviour, even though a prompter and more intense wing fanning courtship behaviour was registered in the ND/NE males compared to males from the AD/NE treatment. These results show that sexual behaviours are less

  20. Decreased functional connectivity in dorsolateral prefrontal cortical networks in adult macaques with neonatal hippocampal lesions: Relations to visual working memory deficits.

    PubMed

    Meng, Yuguang; Hu, Xiaoping; Bachevalier, Jocelyne; Zhang, Xiaodong

    2016-10-01

    Neonatal hippocampal lesions in monkeys impairs normal performance on both relational and working memory tasks, suggesting that the early lesions have impacted the normal development of prefrontal-hippocampal functional interactions necessary for normal performance on these tasks. Given that working memory processes engage distributed neuronal networks associated with the prefrontal cortex, it is critical to explore the integrity of distributed neural networks of dorsolateral prefrontal cortex (dlPFC) following neonatal hippocampal lesions in monkeys. We used resting-state functional MRI to assess functional connectivity of dlPFC networks in monkeys with neonatal neurotoxic hippocampal lesion (Neo-Hibo, n=4) and sham-operated control animals (Neo-C, n=4). Significant differences in the patterns of dlPFC functional networks were found between Groups Neo-Hibo and Neo-C. The within-group maps and the between-group comparisons yielded a highly coherent picture showing altered interactions of core regions of the working memory network (medial prefrontal cortex and posterior parietal cortex) as well as the dorsal (fundus of superior temporal area and superior temporal cortex) and ventral (V4 and infero-temporal cortex) visual processing areas in animals with Neo-Hibo lesions. Correlations between functional connectivity changes and working memory impairment in the same animals were found only between the dlPFC and visual cortical areas (V4 and infero-temporal cortex). Thus, the impact of the neonatal hippocampal lesions extends to multiple cortical areas interconnected with the dlPFC.

  1. Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective

    PubMed Central

    Puri, Rohan; Hinder, Mark R.; Fujiyama, Hakuei; Gomez, Rapson; Carson, Richard G.; Summers, Jeffery J.

    2015-01-01

    The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations. PMID

  2. Older Adults Benefit from Music Training Early in Life: Biological Evidence for Long-Term Training-Driven Plasticity

    PubMed Central

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

    2013-01-01

    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. PMID:24198359

  3. Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats.

    PubMed

    Demir Özkay, Ümide; Söztutar, Erdem; Can, Özgür Devrim; Üçel, Umut İrfan; Öztürk, Yusuf; Ulupinar, Emel

    2015-08-01

    Agomelatine is an antidepressant with a distinct pharmacological mechanism of action as an MT1 and MT2 receptor agonist and as a 5-HT2C receptor antagonist. We evaluated the chronic effects of agomelatine administration (40 mg/kg, 20 weeks) on the cognitive performance of rats in the Morris water maze task. We applied unbiased stereological quantification methods to estimate the total numbers of granular and pyramidal neurons located in the dorsal hippocampus. We also analyzed the dendritic spines of pyramidal neurons in the CA1 region using the Golgi-Cox impregnation method. The agomelatine-treated group found the hidden platform more quickly than did the control group and spent significantly more time in the target quadrant. Agomelatine administration caused significant volumetric and numerical enhancements in granular and pyramidal neurons in the dentate gyrus and CA1-3 subregions, respectively. Increased densities of the mushroom and stubby types of spines, with no alteration in the thin-shaped spines, were observed in the agomelatine-treated group. These results showed that long-term agomelatine administration induced a nootropic effect supported by structural changes. Enhancement of the more stable types of dendritic spines might indicate improved adaptive capacity in hippocampal neurons. Future studies will provide a better understanding of the effect of this drug on synaptic plasticity. PMID:26110225

  4. Transient prenatal vitamin D deficiency is associated with changes of synaptic plasticity in the dentate gyrus in adult rats.

    PubMed

    Grecksch, Gisela; Rüthrich, Heinz; Höllt, Volker; Becker, Axel

    2009-12-01

    Transient prenatal vitamin D deficiency is considered a neurodevelopmental animal model in schizophrenia research. Vitamin D deficiency in female rats causes morphological, cellular and molecular changes in the brain and alters behaviour and nerve growth factors expression in their offspring. Prenatal depleted animals showed a significant impairment of latent inhibition, a feature often associated with schizophrenia and of hole board habituation. Interestingly, memory consolidation of brightness discrimination was improved. Possible functional effects of altered brain development that results from prenatal vitamin D deficiency were characterized by investigation of potentiation phenomena in the hippocampus in freely moving rats. Transient prenatal vitamin D deficiency induced an enhancement of long-term potentiation (LTP) using either weak tetanic or strong tetanic stimulation, whereas the response to test stimuli was not changed. The classic neuroleptic drug haloperidol (Hal) and the atypical neuroleptic risperidone (Ris) in doses, which normalized behavioural disturbances in prenatal vitamin D-deficient animals without any side effects on the normal behaviour decreased the enhanced LTP in the experimental group to control level. Interestingly, the effect of the substances was different in experimental and control rats. The LTP was enhanced in control animals by the low doses of the drugs effective in our behavioural experiments. It can be suggested, that changes in brain development induced by prenatal vitamin D deficiency lead to specific functional alterations in hippocampal synaptic plasticity. LTP is considered a cellular correlate of learning and memory. The better retention performance in brightness discrimination seems in accordance with enhanced potentiation level. PMID:19647946

  5. Evolution of phenotypic plasticity in colonizing species.

    PubMed

    Lande, Russell

    2015-05-01

    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life.

  6. Decreased functional connectivity in dorsolateral prefrontal cortical networks in adult macaques with neonatal hippocampal lesions: Relations to visual working memory deficits.

    PubMed

    Meng, Yuguang; Hu, Xiaoping; Bachevalier, Jocelyne; Zhang, Xiaodong

    2016-10-01

    Neonatal hippocampal lesions in monkeys impairs normal performance on both relational and working memory tasks, suggesting that the early lesions have impacted the normal development of prefrontal-hippocampal functional interactions necessary for normal performance on these tasks. Given that working memory processes engage distributed neuronal networks associated with the prefrontal cortex, it is critical to explore the integrity of distributed neural networks of dorsolateral prefrontal cortex (dlPFC) following neonatal hippocampal lesions in monkeys. We used resting-state functional MRI to assess functional connectivity of dlPFC networks in monkeys with neonatal neurotoxic hippocampal lesion (Neo-Hibo, n=4) and sham-operated control animals (Neo-C, n=4). Significant differences in the patterns of dlPFC functional networks were found between Groups Neo-Hibo and Neo-C. The within-group maps and the between-group comparisons yielded a highly coherent picture showing altered interactions of core regions of the working memory network (medial prefrontal cortex and posterior parietal cortex) as well as the dorsal (fundus of superior temporal area and superior temporal cortex) and ventral (V4 and infero-temporal cortex) visual processing areas in animals with Neo-Hibo lesions. Correlations between functional connectivity changes and working memory impairment in the same animals were found only between the dlPFC and visual cortical areas (V4 and infero-temporal cortex). Thus, the impact of the neonatal hippocampal lesions extends to multiple cortical areas interconnected with the dlPFC. PMID:27063864

  7. A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats.

    PubMed

    Miyagawa, Kazuaki; Kozai, Yusuke; Ito, Yumi; Furuhama, Takami; Naruse, Kouji; Nonaka, Kiichi; Nagai, Yumiko; Yamato, Hideyuki; Kashima, Isamu; Ohya, Keiichi; Aoki, Kazuhiro; Mikuni-Takagaki, Yuko

    2011-07-01

    Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical. PMID:21127921

  8. Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence.

    PubMed

    Mastwal, Surjeet; Ye, Yizhou; Ren, Ming; Jimenez, Dennisse V; Martinowich, Keri; Gerfen, Charles R; Wang, Kuan Hong

    2014-07-16

    The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in humans. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Using optogenetic stimulation and in vivo two-photon imaging in adolescent mice, we found that phasic, but not tonic, dopamine neuron activity induces the formation of mesofrontal axonal boutons. In contrast, in adult mice, the effect of phasic activity diminishes. Furthermore, our results showed that dopaminergic and glutamatergic transmission regulate this axonal plasticity in adolescence and inhibition of dopamine D2-type receptors restores this plasticity in adulthood. Finally, we found that phasic activation of dopamine neurons also induces greater changes in mesofrontal circuit activity and psychomotor response in adolescent mice than in adult mice. Together, our findings demonstrate that the structure and function of the mesofrontal circuit are modifiable by phasic activity in dopaminergic neurons during adolescence and suggest that the greater plasticity in adolescence may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control.

  9. Structural Plasticity, Effectual Connectivity, and Memory in Cortex

    PubMed Central

    Knoblauch, Andreas; Sommer, Friedrich T.

    2016-01-01

    Learning and memory is commonly attributed to the modification of synaptic strengths in neuronal networks. More recent experiments have also revealed a major role of structural plasticity including elimination and regeneration of synapses, growth and retraction of dendritic spines, and remodeling of axons and dendrites. Here we work out the idea that one likely function of structural plasticity is to increase “effectual connectivity” in order to improve the capacity of sparsely connected networks to store Hebbian cell assemblies that are supposed to represent memories. For this we define effectual connectivity as the fraction of synaptically linked neuron pairs within a cell assembly representing a memory. We show by theory and numerical simulation the close links between effectual connectivity and both information storage capacity of neural networks and effective connectivity as commonly employed in functional brain imaging and connectome analysis. Then, by applying our model to a recently proposed memory model, we can give improved estimates on the number of cell assemblies that can be stored in a cortical macrocolumn assuming realistic connectivity. Finally, we derive a simplified model of structural plasticity to enable large scale simulation of memory phenomena, and apply our model to link ongoing adult structural plasticity to recent behavioral data on the spacing effect of learning. PMID:27378861

  10. Structural Plasticity, Effectual Connectivity, and Memory in Cortex.

    PubMed

    Knoblauch, Andreas; Sommer, Friedrich T

    2016-01-01

    Learning and memory is commonly attributed to the modification of synaptic strengths in neuronal networks. More recent experiments have also revealed a major role of structural plasticity including elimination and regeneration of synapses, growth and retraction of dendritic spines, and remodeling of axons and dendrites. Here we work out the idea that one likely function of structural plasticity is to increase "effectual connectivity" in order to improve the capacity of sparsely connected networks to store Hebbian cell assemblies that are supposed to represent memories. For this we define effectual connectivity as the fraction of synaptically linked neuron pairs within a cell assembly representing a memory. We show by theory and numerical simulation the close links between effectual connectivity and both information storage capacity of neural networks and effective connectivity as commonly employed in functional brain imaging and connectome analysis. Then, by applying our model to a recently proposed memory model, we can give improved estimates on the number of cell assemblies that can be stored in a cortical macrocolumn assuming realistic connectivity. Finally, we derive a simplified model of structural plasticity to enable large scale simulation of memory phenomena, and apply our model to link ongoing adult structural plasticity to recent behavioral data on the spacing effect of learning. PMID:27378861

  11. Hormone-dependent neural plasticity in the juvenile and adult song system: what makes a successful male?

    PubMed

    Gahr, Manfred

    2004-06-01

    The sexual quality of adult song is the result of genetic and epigenetic mechanisms shaping the neural song system throughout life. Genetic brain-intrinsic mechanisms determine the neuron pools that develop into forebrain song control areas independent of gonadal steroid hormones, androgens and estrogens. One fate of these neurons is the potential to express sex steroid receptors, such as androgen and estrogen receptors. Genetic brain-intrinsic mechanisms, too, determine the activity of hypothalamic-pituitary-gonad (HPG) axis, i.e., the working range and responsiveness of HPG axis to produce gonadal hormones. The epigenetic action of gonadal steroid hormones (androgens and estrogens) on determined vocal neurons is required to maintain and increase the pool of determined vocal neurons and to complete the connections of the vocal system, i.e., to make it function motorically. The subsequent influence of environmental information, including both external (socio-sexual and physical) and internal (body physiology) signals, specify the further neural phenotype of vocal areas either through acting on the HPG axis and differential release of gonadal hormones or through non-gonadal hormone systems, both of which have target neurons in the functional vocal system. Despite the clear evidence of hormone dependency of the development of both the adult song phenotype and song system phenotype, their causal relation is complex.

  12. Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain.

    PubMed

    Kim, Sun Kwang; Hayashi, Hideaki; Ishikawa, Tatsuya; Shibata, Keisuke; Shigetomi, Eiji; Shinozaki, Youichi; Inada, Hiroyuki; Roh, Seung Eon; Kim, Sang Jeong; Lee, Gihyun; Bae, Hyunsu; Moorhouse, Andrew J; Mikoshiba, Katsuhiko; Fukazawa, Yugo; Koizumi, Schuichi; Nabekura, Junichi

    2016-05-01

    Long-term treatments to ameliorate peripheral neuropathic pain that includes mechanical allodynia are limited. While glial activation and altered nociceptive transmission within the spinal cord are associated with the pathogenesis of mechanical allodynia, changes in cortical circuits also accompany peripheral nerve injury and may represent additional therapeutic targets. Dendritic spine plasticity in the S1 cortex appears within days following nerve injury; however, the underlying cellular mechanisms of this plasticity and whether it has a causal relationship to allodynia remain unsolved. Furthermore, it is not known whether glial activation occurs within the S1 cortex following injury or whether it contributes to this S1 synaptic plasticity. Using in vivo 2-photon imaging with genetic and pharmacological manipulations of murine models, we have shown that sciatic nerve ligation induces a re-emergence of immature metabotropic glutamate receptor 5 (mGluR5) signaling in S1 astroglia, which elicits spontaneous somatic Ca2+ transients, synaptogenic thrombospondin 1 (TSP-1) release, and synapse formation. This S1 astrocyte reactivation was evident only during the first week after injury and correlated with the temporal changes in S1 extracellular glutamate levels and dendritic spine turnover. Blocking the astrocytic mGluR5-signaling pathway suppressed mechanical allodynia, while activating this pathway in the absence of any peripheral injury induced long-lasting (>1 month) allodynia. We conclude that reawakened astrocytes are a key trigger for S1 circuit rewiring and that this contributes to neuropathic mechanical allodynia. PMID:27064281

  13. Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain

    PubMed Central

    Hayashi, Hideaki; Ishikawa, Tatsuya; Shibata, Keisuke; Inada, Hiroyuki; Roh, Seung Eon; Kim, Sang Jeong; Moorhouse, Andrew J.

    2016-01-01

    Long-term treatments to ameliorate peripheral neuropathic pain that includes mechanical allodynia are limited. While glial activation and altered nociceptive transmission within the spinal cord are associated with the pathogenesis of mechanical allodynia, changes in cortical circuits also accompany peripheral nerve injury and may represent additional therapeutic targets. Dendritic spine plasticity in the S1 cortex appears within days following nerve injury; however, the underlying cellular mechanisms of this plasticity and whether it has a causal relationship to allodynia remain unsolved. Furthermore, it is not known whether glial activation occurs within the S1 cortex following injury or whether it contributes to this S1 synaptic plasticity. Using in vivo 2-photon imaging with genetic and pharmacological manipulations of murine models, we have shown that sciatic nerve ligation induces a re-emergence of immature metabotropic glutamate receptor 5 (mGluR5) signaling in S1 astroglia, which elicits spontaneous somatic Ca2+ transients, synaptogenic thrombospondin 1 (TSP-1) release, and synapse formation. This S1 astrocyte reactivation was evident only during the first week after injury and correlated with the temporal changes in S1 extracellular glutamate levels and dendritic spine turnover. Blocking the astrocytic mGluR5-signaling pathway suppressed mechanical allodynia, while activating this pathway in the absence of any peripheral injury induced long-lasting (>1 month) allodynia. We conclude that reawakened astrocytes are a key trigger for S1 circuit rewiring and that this contributes to neuropathic mechanical allodynia. PMID:27064281

  14. Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury.

    PubMed

    Wang, Hongxing; Liu, Nai-Kui; Zhang, Yi Ping; Deng, Lingxiao; Lu, Qing-Bo; Shields, Christopher B; Walker, Melissa J; Li, Jianan; Xu, Xiao-Ming

    2015-09-01

    Spinal cord injury (SCI) is devastating, causing sensorimotor impairments and paralysis. Persisting functional limitations on physical activity negatively affect overall health in individuals with SCI. Physical training may improve motor function by affecting cellular and molecular responses of motor pathways in the central nervous system (CNS) after SCI. Although motoneurons form the final common path for motor output from the CNS, little is known concerning the effect of exercise training on spared motoneurons below the level of injury. Here we examined the effect of treadmill training on morphological, trophic, and synaptic changes in the lumbar motoneuron pool and on behavior recovery after a moderate contusive SCI inflicted at the 9th thoracic vertebral level (T9) using an Infinite Horizon (IH, 200 kDyne) impactor. We found that treadmill training significantly improved locomotor function, assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale, and reduced foot drops, assessed by grid walking performance, as compared with non-training. Additionally, treadmill training significantly increased the total neurite length per lumbar motoneuron innervating the soleus and tibialis anterior muscles of the hindlimbs as compared to non-training. Moreover, treadmill training significantly increased the expression of a neurotrophin brain-derived neurotrophic factor (BDNF) in the lumbar motoneurons as compared to non-training. Finally, treadmill training significantly increased synaptic density, identified by synaptophysin immunoreactivity, in the lumbar motoneuron pool as compared to non-training. However, the density of serotonergic terminals in the same regions did not show a significant difference between treadmill training and non-training. Thus, our study provides a biological basis for exercise training as an effective medical practice to improve recovery after SCI. Such an effect may be mediated by synaptic plasticity, and neurotrophic modification in the

  15. Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury.

    PubMed

    Wang, Hongxing; Liu, Nai-Kui; Zhang, Yi Ping; Deng, Lingxiao; Lu, Qing-Bo; Shields, Christopher B; Walker, Melissa J; Li, Jianan; Xu, Xiao-Ming

    2015-09-01

    Spinal cord injury (SCI) is devastating, causing sensorimotor impairments and paralysis. Persisting functional limitations on physical activity negatively affect overall health in individuals with SCI. Physical training may improve motor function by affecting cellular and molecular responses of motor pathways in the central nervous system (CNS) after SCI. Although motoneurons form the final common path for motor output from the CNS, little is known concerning the effect of exercise training on spared motoneurons below the level of injury. Here we examined the effect of treadmill training on morphological, trophic, and synaptic changes in the lumbar motoneuron pool and on behavior recovery after a moderate contusive SCI inflicted at the 9th thoracic vertebral level (T9) using an Infinite Horizon (IH, 200 kDyne) impactor. We found that treadmill training significantly improved locomotor function, assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale, and reduced foot drops, assessed by grid walking performance, as compared with non-training. Additionally, treadmill training significantly increased the total neurite length per lumbar motoneuron innervating the soleus and tibialis anterior muscles of the hindlimbs as compared to non-training. Moreover, treadmill training significantly increased the expression of a neurotrophin brain-derived neurotrophic factor (BDNF) in the lumbar motoneurons as compared to non-training. Finally, treadmill training significantly increased synaptic density, identified by synaptophysin immunoreactivity, in the lumbar motoneuron pool as compared to non-training. However, the density of serotonergic terminals in the same regions did not show a significant difference between treadmill training and non-training. Thus, our study provides a biological basis for exercise training as an effective medical practice to improve recovery after SCI. Such an effect may be mediated by synaptic plasticity, and neurotrophic modification in the

  16. A Cross-Sectional Study of the Relationship between Cortical Bone and High-Impact Activity in Young Adult Males and Females

    PubMed Central

    Deere, K.; Sayers, A.; Rittweger, J.

    2012-01-01

    Context: The factors that govern skeletal responses to physical activity remain poorly understood. Objective: The aim of this study was to investigate whether gender or fat mass influences relationships between cortical bone and physical activity, after partitioning accelerometer outputs into low (0.5–2.1 g), medium (2.1–4.2 g), or high (>4.2 g) impacts, where g represents gravitational force. Design/Setting: We conducted a cross-sectional analysis in participants from the Avon Longitudinal Study of Parents and Children. Participants: We studied 675 adolescents (272 boys; mean age, 17.7 yr). Outcome Measures: We measured cortical bone parameters from peripheral quantitative computed tomography scans of the mid-tibia, adjusted for height, fat mass, and lean mass. Results: High-impact activity was positively associated with periosteal circumference (PC) in males but not females [coefficients (95% confidence intervals), 0.054 (0.007, 0.100) and 0.07 (−0.028, 0.041), respectively; showing sd change per doubling in activity]. There was also weak evidence that medium impacts were positively related to PC in males but not females (P = 0.03 for gender interaction). On stratifying by fat mass, the positive relationship between high-impact activity and PC was greatest in those with the highest fat mass [high impact vs. PC in males, 0.01 (−0.064, 0.085), 0.045 (−0.040, 0.131), 0.098 (0.012, 0.185), for lower, middle, and upper fat tertiles, respectively; high impact vs. PC in females, −0.041 (−0.101, 0.020), −0.028 (−0.077, 0.022), 0.082 (0.015, 0.148), P = 0.01 for fat mass interaction]. Similar findings were observed for strength parameters, cross-sectional moment of inertia, and strength-strain index. Conclusions: In late adolescence, associations between high-impact activity and PC are attenuated by female gender and low body fat, suggesting that the skeletal response to high-impact activity is particularly reduced in young women with low fat mass. PMID

  17. Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity relative to hypertension alone in older adults

    PubMed Central

    Tchistiakova, Ekaterina; Anderson, Nicole D.; Greenwood, Carol E.; MacIntosh, Bradley J.

    2014-01-01

    Objective Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. Research design and methods We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Gray matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. Results Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P < 0.025); CVR group differences were more expansive and included bilateral occipito-parietal areas (P < 0.025). Whereas CVR showed no significant associations with measures of cognitive function (P > 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, and middle and inferior temporal regions (P < 0.025) were associated with executive function. Conclusions Individuals with T2DM and HTN showed decreased CVR and CThk compared to age-matched HTN controls. This study identifies brain regions that are impacted by the combined effects of comorbid T2DM and HTN conditions, with new evidence that the corresponding cortical thinning may contribute to cognitive decline. PMID:24967157

  18. Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex

    PubMed Central

    Bloss, Erik B.; Janssen, William G.; Ohm, Daniel T.; Yuk, Frank J.; Wadsworth, Shannon; Saardi, Karl M.; McEwen, Bruce S.; Morrison, John H.

    2011-01-01

    Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, non-human primates, and rodents, although the neurobiological correlates of this vulnerability remain largely unknown. It has been proposed that dendritic spines represent the primary site of structural plasticity in the adult brain, and recent data have supported the hypothesis that aging is associated with alterations of dendritic spine morphology and plasticity in prefrontal cortex. However, no study to date has directly examined whether aging alters the capacity for experience-dependent spine plasticity in aging prefrontal neurons. To address this possibility we used young, middle-aged, and aged rats in a behavioral stress paradigm known to produce spine remodeling in prefrontal cortical neurons. In young rats, stress resulted in dendritic spine loss and altered patterns of spine morphology; in contrast, spines from middle-aged and aged animals were remarkably stable and did not show evidence of remodeling. The loss of stress-induced spine plasticity observed in aging rats occurred alongside robust age-related reductions in spine density and shifts in remaining spine morphology. Taken together, the data presented here provide the first evidence that experience-dependent spine plasticity is altered by aging in prefrontal cortex, and support a model in which dendritic spines become progressively less plastic in the aging brain. PMID:21613496

  19. Cortical Excitability During Passive Action Observation in Hospitalized Adults With Subacute Moderate to Severe Traumatic Brain Injury: A Preliminary TMS Study.

    PubMed

    Fecteau, Shirley; Dickler, Maya; Pelayo, Raul; Kumru, Hatice; Bernabeu, Monste; Opisso Salleras, Eloy; Tormos, José Maria; Pascual-Leone, Alvaro

    2015-07-01

    Studies indicate that motor functions in patients with traumatic brain injury (TBI) can be improved with action observation. It has been hypothesized that this clinical practice relies on modulation of motor cortical excitability elicited by passive action observation in patients with TBI, a phenomenon shown thus far only in normal controls. The purpose of this work was to test this hypothesis and characterize the modulation of motor cortex excitability during passive action observation in patients with subacute moderate to severe TBI. We measured motor evoked potentials induced by single-pulse transcranial magnetic stimulation to the left primary motor cortex and recorded from the contralateral first dorsal interosseus while 20 participants observed videos of static and moving right index finger. Results were compared with those of 20 age-and gender-matched healthy controls. As expected, greater excitability was elicited during moving than static stimuli in healthy subjects. However, this was not observed in patients with TBI. Modulation of motor excitability during action observation is impaired in patients with TBI depending on motor dysfunction, lesion site, and number of days postinjury. These preliminary results suggest a strategy to identify patients in whom action observation might be a valuable neurorehabilitative strategy. PMID:25505219

  20. Effect of pycnogenol and spirulina on vancomycin-induced renal cortical oxidative stress, apoptosis, and autophagy in adult male albino rat.

    PubMed

    Bayomy, Naglaa A; Abdelaziz, Eman Z; Said, Mona A; Badawi, Marwa S; El-Bakary, Reda H

    2016-08-01

    Vancomycin-induced nephrotoxicity has been reported to occur in 5%-25% of patients who were administered with it. Several natural antioxidants were found to be effective against drug-induced toxicity. We evaluated the possible protective effects of spirulina and pycnogenol alone or in combination on vancomycin-induced renal cortical oxidative stress. Forty-nine rats were randomly divided into 7 groups: group I, control; group II, received spirulina 1000 mg/kg per day; group III, received pycnogenol 200 mg/kg per day; group IV, received vancomycin 200 mg/kg per day every 12 h; group V, (spirulina + vancomycin); group VI, (pycnogenol + vancomycin); and group VII, (pycnogenol + spirulina + vancomycin). At the end of the experiment, kidney functions were estimated and then the kidneys were removed, weighed, and sampled for histopathological, immunohistochemistry, and biochemical studies. Administration of spirulina and pycnogenol alone or in combination decreased elevated serum creatinine, blood urea nitrogen, renal malondialdehyde, and immunoexpression of the proapoptotic protein (Bax), autophagic marker protein (LC3/B), and inducible nitric oxide synthase induced by vancomycin. They increased reduced glutathione, glutathione peroxidase, superoxide dismutase, and immunoexpression of the antiapoptotic protein (Bcl2). They also ameliorated the morphological changes induced by vancomycin. The combination therapy of spirulina and pycnogenol showed better protective effects than the corresponding monotherapy. PMID:27203524

  1. Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity

    PubMed Central

    Chew, Benjamin; Ryu, Jae Ryun; Ng, Teclise; Ma, Dongliang; Dasgupta, Ananya; Neo, Sin Hui; Zhao, Jing; Zhong, Zhong; Bichler, Zoë; Sajikumar, Sreedharan; Goh, Eyleen L. K.

    2015-01-01

    Attempts have been made to use glycogen synthase kinase-3 beta (GSK3β) inhibitors for prophylactic treatment of neurocognitive conditions. However the use of lithium, a non-specific inhibitor of GSK3β results in mild cognitive impairment in humans. The effects of global GSK3β inhibition or knockout on learning and memory in healthy adult mice are also inconclusive. Our study aims to better understand the role of GSK3β in learning and memory through a more regionally, targeted approach, specifically performing lentiviral-mediated knockdown of GSK3β within the dentate gyrus (DG). DG-GSK3β-silenced mice showed impaired contextual fear memory retrieval. However, cue fear memory, spatial memory, locomotor activity and anxiety levels were similar to control. These GSK3β-silenced mice also showed increased induction and maintenance of DG long-term potentiation (DG-LTP) compared to control animals. Thus, this region-specific, targeted knockdown of GSK3β in the DG provides better understanding on the role of GSK3β in learning and memory. PMID:26157370

  2. Plastic Jellyfish.

    ERIC Educational Resources Information Center

    Moseley, Christine

    2000-01-01

    Presents an environmental science activity designed to enhance students' awareness of the hazards of plastic waste for wildlife in aquatic environments. Discusses how students can take steps to reduce the effects of plastic waste. (WRM)

  3. Auditory Cortex Mapmaking: Principles, Projections, and Plasticity

    PubMed Central

    Schreiner, Christoph E.; Winer, Jeffery A.

    2008-01-01

    Maps of sensory receptor epithelia and of derived or computed features of the sensory environment are a common feature of auditory, visual, and somatic sensory representations from the periphery to the cerebral cortex. Maps enhance the understanding of normal neural organization and its modification by pathology and experience. They underlie the derivation of the computational principles that govern sensory processing and the generation of perception. Despite their intuitive explanatory power, the functio of and rules for organizing maps and their plasticity are not well understood. Some puzzles of auditory cortical map organization are that only a few complete receptor maps are available, and that even fewer computational maps have been identified beyond primary cortical areas. Neuroanatomical evidence suggests equally organized connectional patterns throughout the cortical hierarchy that might nerlie map stability. Here we consider the implications of auditory cortical map organization and its plasticity and evaluate the complementary role of maps in representation and computation from an auditory perspective. PMID:17964251

  4. Development of Cortical Circuitry and Cognitive Function.

    ERIC Educational Resources Information Center

    Goldman-Rakic, Patricia S.

    1987-01-01

    Recent studies on the biological development of the prefrontal cortex in rhesus monkeys are reviewed. These studies have elucidated the basic neural circuitry underlying the delayed-response function in adult nonhuman primates and suggest that a critical mass of cortical synapses is important for the emergence of this cognitive function. (BN)

  5. Noradrenaline depletion blocks behavioral sparing and alters cortical morphogenesis after neonatal frontal cortex damage in rats.

    PubMed

    Kolb, B; Sutherland, R J

    1992-06-01

    The possibility that cortical noradrenaline (NA) is necessary for sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage on postnatal day 7 (P7) was better than that by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical NA by means of neonatal 6-hydroxydopamine (6HDA) administration. The blockade of sparing in the P7 frontal operates was associated with a smaller brain, thinner cortex, and reduced cortical dendritic branching relative to saline-treated P7 frontal operates. NA depletion alone in unoperated rats did not affect spatial learning but did reduce brain size and dendritic branching. Rats with frontal lesions on P4 did not show sparing of spatial localization, and 6HDA administration had no additional behavioral effect. Overall, these data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex. PMID:1607943

  6. Neonatal cortical ablation disrupts multisensory development in superior colliculus

    PubMed Central

    Jiang, Wan; Jiang, Huai; Stein, Barry E.

    2006-01-01

    The ability of cat superior colliculus (SC) neurons to synthesize information from different senses depends on influences from two areas of the cortex: the anterior ectosylvian sulcus (AES) and the rostral lateral suprasylvian sulcus (rLS). Reversibly deactivating the inputs to the SC from either of these areas in normal adults severely compromises this ability and the SC-mediated behaviors that depend on it. In the present study we found that removal of these areas in neonatal animals precluded the normal development of multisensory SC processes. At maturity there was a substantial decrease in the incidence of multisensory neurons, and those multisensory neurons that did develop were highly abnormal. Their cross-modal receptive field register was severely compromised, as was their ability to integrate cross-modal stimuli. Apparently, despite the impressive plasticity of the neonatal brain, it cannot compensate for the early loss of these cortices. Surprisingly, however, neonatal removal of either AES or rLS had comparatively minor consequences on these properties. At maturity multisensory SC neurons were quite common: they developed the characteristic spatial register among their unisensory receptive fields and exhibited normal adult-like multisensory integration. These observations suggest that during early ontogeny, when the multisensory properties of SC neurons are being crafted, AES and rLS may have the ability to compensate for the loss of one another’s cortico-collicular influences so that normal multisensory processes can develop in the SC. PMID:16267111

  7. Compensatory plasticity: time matters.

    PubMed

    Lazzouni, Latifa; Lepore, Franco

    2014-01-01

    Plasticity in the human and animal brain is the rule, the base for development, and the way to deal effectively with the environment for making the most efficient use of all the senses. When the brain is deprived of one sensory modality, plasticity becomes compensatory: the exception that invalidates the general loss hypothesis giving the opportunity of effective change. Sensory deprivation comes with massive alterations in brain structure and function, behavioral outcomes, and neural interactions. Blind individuals do as good as the sighted and even more, show superior abilities in auditory, tactile and olfactory processing. This behavioral enhancement is accompanied with changes in occipital cortex function, where visual areas at different levels become responsive to non-visual information. The intact senses are in general used more efficiently in the blind but are also used more exclusively. New findings are disentangling these two aspects of compensatory plasticity. What is due to visual deprivation and what is dependent on the extended use of spared modalities? The latter seems to contribute highly to compensatory changes in the congenitally blind. Short-term deprivation through the use of blindfolds shows that cortical excitability of the visual cortex is likely to show rapid modulatory changes after few minutes of light deprivation and therefore changes are possible in adulthood. However, reorganization remains more pronounced in the congenitally blind. Cortico-cortical pathways between visual areas and the areas of preserved sensory modalities are inhibited in the presence of vision, but are unmasked after loss of vision or blindfolding as a mechanism likely to drive cross-modal information to the deafferented visual cortex. The development of specialized higher order visual pathways independently from early sensory experience is likely to preserve their function and switch to the intact modalities. Plasticity in the blind is also accompanied with

  8. Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study

    PubMed Central

    Duncan, Niall W.; Hayes, Dave J.; Wiebking, Christine; Tiret, Brice; Pietruska, Karin; Chen, David Q.; Rainville, Pierre; Marjańska, Malgorzata; Mohammid, Omar; Doyon, Julien; Hodaie, Mojgan; Northoff, Georg

    2016-01-01

    Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain’s resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. PMID:26287448

  9. Alteration of Cingulate Long-Term Plasticity and Behavioral Sensitization to Inflammation by Environmental Enrichment

    ERIC Educational Resources Information Center

    Shum, Fanny W. F.; Wu, Long-Jun; Zhao, Ming-Gao; Toyoda, Hiroki; Xu, Hui; Ren, Ming; Pinaud, Raphael; Ko, Shanelle W.; Lee, Yong-Seok; Kaang, Bong-Kiun; Zhuo, Min

    2007-01-01

    Exposure to an enriched environment (EE) has been shown to induce cortical plasticity. Considerable amount of research is focused on the effects of EE in the hippocampus; however, effects of EE on other brain regions and the mechanisms involved are not well known. To investigate this, we induced cortical plasticity by placing mice in an EE for one…

  10. Ratio between mature and immature enzymatic cross-links correlates with post-yield cortical bone behavior: An insight into greenstick fractures of the child fibula.

    PubMed

    Berteau, Jean-Philippe; Gineyts, Evelyne; Pithioux, Martine; Baron, Cécile; Boivin, Georges; Lasaygues, Philippe; Chabrand, Patrick; Follet, Hélène

    2015-10-01

    As a determinant of skeletal fragility, the organic matrix is responsible for the post-yield and creep behavior of bone and for its toughness, while the mineral apatite acts on stiffness. Specific to the fibula and ulna in children, greenstick fractures show a plastic in vivo mechanical behavior before bone fracture. During growth, the immature form of collagen enzymatic cross-links gradually decreases, to be replaced by the mature form until adolescence, subsequently remaining constant throughout adult life. However, the link between the cortical bone organic matrix and greenstick fractures in children remains to be explored. Here, we sought to determine: 1) whether plastic bending fractures can occur in vitro, by testing cortical bone samples from children's fibula and 2) whether the post-yield behavior (ωp plastic energy) of cortical bone before fracture is related to total quantity of the collagen matrix, or to the quantity of mature and immature enzymatic cross-links and the quantity of non-enzymatic cross-links. We used a two-step approach; first, a 3-point microbending device tested 22 fibula machined bone samples from 7 children and 3 elderly adults until fracture. Second, biochemical analysis by HPLC was performed on the sample fragments. When pooling two groups of donors, children and elderly adults, results show a rank correlation between total energy dissipated before fracture and age and a linear correlation between plastic energy dissipated before fracture and ratio of immature/mature cross-links. A collagen matrix with more immature cross-links (i.e. a higher immature/mature cross-link ratio) is more likely to plastically deform before fracture. We conclude that this ratio in the sub-nanostructure of the organic matrix in cortical bone from the fibula may go some way towards explaining the variance in post-yield behavior. From a clinical point of view, therefore, our results provide a potential explanation of the presence of greenstick fractures in

  11. Experience-dependent gene expression in adult visual cortex.

    PubMed

    Chen, Jiabin; Yamahachi, Homare; Gilbert, Charles D

    2010-03-01

    Experience-dependent plasticity of the adult visual cortex underlies perceptual learning and recovery of function following central nervous system lesions. To reveal the signal transduction cascades involved in adult cortical plasticity, we utilized a model of remapping of cortical topography following binocular retinal lesions. In this model, the lesion projection zone (LPZ) of primary visual cortex (V1) recovers visually driven activity by the sprouting of horizontal axonal connections originating from the cells in the surrounding region. To explore the molecular mechanism underlying this process, we used gene microarrays from an expression library prepared from Macaque V1. By microarray analysis of gene expression levels in the LPZ and the surrounding region, and subsequent confirmation with Quantitative Real-Time polymerase chain reaction and in situ hybridization, the participation of a number of genes was observed, including the Rho GTPase family. Its role in regulation of cytoskeleton assembly provides a possible link between the alteration of neural activity and cortical functional reorganization. PMID:19571270

  12. Processing demands upon cognitive, linguistic, and articulatory functions promote grey matter plasticity in the adult multilingual brain: Insights from simultaneous interpreters.

    PubMed

    Elmer, Stefan; Hänggi, Jürgen; Jäncke, Lutz

    2014-05-01

    Until now, considerable effort has been made to determine structural brain characteristics related to exceptional multilingual skills. However, at least one important question has not yet been satisfactorily addressed in the previous literature, namely whether and to which extent the processing demands upon cognitive, linguistic, and articulatory functions may promote grey matter plasticity in the adult multilingual brain. Based on the premise that simultaneous interpretation is a highly demanding linguistic task that places strong demands on executive and articulatory functions, here we compared grey matter volumes between professional simultaneous interpreters (SI) and multilingual control subjects. Thereby, we focused on a specific set of a-priori defined bilateral brain regions that have previously been shown to support neurocognitional aspects of language control and linguistic functions in the multilingual brain. These regions are the cingulate gyrus, caudate nucleus, frontal operculum (pars triangularis and opercularis), inferior parietal lobe (IPL) (supramarginal and angular gyrus), and the insula. As a main result, we found reduced grey matter volumes in professional SI, compared to multilingual controls, in the left middle-anterior cingulate gyrus, bilateral pars triangularis, left pars opercularis, bilateral middle part of the insula, and in the left supramarginal gyrus (SMG). Interestingly, grey matter volume in left pars triangularis, right pars opercularis, middle-anterior cingulate gyrus, and in the bilateral caudate nucleus was negatively correlated with the cumulative number of interpreting hours. Hence, we provide first evidence for an expertise-related grey matter architecture that may reflect a composite of brain characteristics that were still present before interpreting training and training-related changes.

  13. The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy.

    PubMed

    Vaca, Alicia Maldré; Guido, Carolina Beatriz; Sosa, Liliana Del Valle; Nicola, Juan Pablo; Mukdsi, Jorge; Petiti, Juan Pablo; Torres, Alicia Ines

    2016-08-01

    Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations. PMID:27302752

  14. The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy.

    PubMed

    Vaca, Alicia Maldré; Guido, Carolina Beatriz; Sosa, Liliana Del Valle; Nicola, Juan Pablo; Mukdsi, Jorge; Petiti, Juan Pablo; Torres, Alicia Ines

    2016-08-01

    Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations.

  15. Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: Relationship to structural plasticity and immediate early gene expression in frontal cortex

    PubMed Central

    Hamilton, Derek A.; Akers, Katherine G.; Rice, James P.; Johnson, Travis E.; Candelaria-Cook, Felicha T.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2009-01-01

    The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24 hours of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior

  16. The descending corticocollicular pathway mediates learning-induced auditory plasticity

    PubMed Central

    Bajo, Victoria M; Nodal, Fernando R; Moore, David R; King, Andrew J

    2013-01-01

    Descending projections from sensory areas of the cerebral cortex are among the largest pathways in the brain, suggesting that they are important for subcortical processing. Although corticofugal inputs have been shown to modulate neuronal responses in the thalamus and midbrain, the behavioral importance of these changes remains unknown. In the auditory system, one of the major descending pathways is from cortical layer V pyramidal cells to the inferior colliculus in the midbrain. We examined the role of these neurons in experience-dependent recalibration of sound localization in adult ferrets by selectively killing the neurons using chromophore-targeted laser photolysis. When provided with appropriate training, animals normally relearn to localize sound accurately after altering the spatial cues available by reversibly occluding one ear. However, this ability was lost after eliminating corticocollicular neurons, whereas normal sound-localization accuracy was unaffected. The integrity of this descending pathway is therefore critical for learning-induced localization plasticity. PMID:20037578

  17. Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity.

    PubMed

    He, Ling-jie; Liu, Nan; Cheng, Tian-lin; Chen, Xiao-jing; Li, Yi-ding; Shu, You-sheng; Qiu, Zi-long; Zhang, Xiao-hui

    2014-10-09

    Mutations in the X-linked gene encoding the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2) impair postnatal development of the brain. Here we use neuronal-type specific gene deletion in mice to show that conditional Mecp2 deletion in GABAergic parvalbumin-expressing (PV) cells (PV-Mecp2(-/y)) does not cause most Rett-syndrome-like behaviours, but completely abolishes experience-dependent critical period plasticity of primary visual cortex (V1) that develops normal visual functions. However, selective loss of Mecp2 in GABAergic somatostatin-expressing cells or glutamatergic pyramidal cells does not affect the critical period plasticity. MeCP2-deficient PV cells exhibit high intrinsic excitability, selectively reduced efficacy of recurrent excitatory synapses in V1 layer 4 circuits, and decreased evoked visual responses in vivo. Enhancing cortical gamma-aminobutyric acid (GABA) inhibition with diazepam infusion can restore critical period plasticity in both young and adult PV-Mecp2(-/y) mice. Thus, MeCP2 expression in inhibitory PV cells during the critical period is essential for local circuit functions underlying experience-dependent cortical plasticity.

  18. Acute stress and hippocampal output: exploring dorsal CA1 and subicular synaptic plasticity simultaneously in anesthetized rats

    PubMed Central

    MacDougall, Matthew J; Howland, John G

    2013-01-01

    The Cornu Ammonis-1 (CA1) subfield and subiculum (SUB) serve as major output structures of the hippocampal formation. Exploring forms of synaptic plasticity simultaneously within these two output regions may improve understanding of the dynamics of hippocampal circuitry and information transfer between hippocampal and cortical brain regions. Using a novel dual-channel electrophysiological preparation in urethane-anesthetized adult male Sprague-Dawley rats in vivo, we examined the effects of acute restraint stress (30 min) on short- and long-term forms of synaptic plasticity in both CA1 and SUB by stimulating the CA3 region. Paired-pulse facilitation was disrupted in SUB but not CA1 in the dual-channel experiments following exposure to acute stress. Disruptions in CA1 PPF were evident in subsequent single-channel experiments with a more anterior recording site. Acute stress disrupted long-term potentiation induced by high-frequency stimulation (10 bursts of 20 pulses at 200 Hz) in both CA1 and SUB. Low-frequency stimulation (900 pulses at 1 Hz) did not alter CA1 plasticity while a late-developing potentiation was evident in SUB that was disrupted following exposure to acute stress. These findings highlight differences in the sensitivity to acute stress for distinct forms of synaptic plasticity within synapses in hippocampal output regions. The findings are discussed in relation to normal and aberrant forms of hippocampal-cortical information processing. PMID:24303119

  19. Plasticity of inhibitory synaptic network interactions in the lateral amygdala upon fear conditioning in mice.

    PubMed

    Szinyei, Csaba; Narayanan, Rajeevan T; Pape, Hans-Christian

    2007-02-01

    After fear conditioning, plastic changes of excitatory synaptic transmission occur in the amygdala. Fear-related memory also involves the GABAergic system, although no influence on inhibitory synaptic transmission is known. In the present study we assessed the influence of Pavlovian fear conditioning on the plasticity of GABAergic synaptic interactions in the lateral amygdala (LA) in brain slices prepared from fear-conditioned, pseudo-trained and naïve adult mice. Theta-burst tetanization of thalamic afferent inputs to the LA evoked an input-specific potentiation of inhibitory postsynaptic responses in projection neurons; the cortical input was unaffected. Philanthotoxin (10 microM), an antagonist of Ca2+-permeable AMPA receptors, disabled this plastic phenomenon. Surgical isolation of the LA, extracellular application of a GABA(B) receptor antagonist (CGP 55845A, 10 microM) or an NMDA receptor antagonist (APV, 50 microM), or intracellular application of BAPTA (10 mM), did not influence the plasticity. The plasticity also showed as a potentiation of monosynaptic excitatory responses in putative GABAergic interneurons. Pavlovian fear conditioning, but not pseudo-conditioning, resulted in a significant reduction in this potentiation that was evident 24 h after training. Two weeks after training, the potentiation returned to control levels. In conclusion, a reduction in potentiation of inhibitory synaptic interactions occurs in the LA and may contribute to a shift in synaptic balance towards excitatory signal flow during the processes of fear-memory acquisition or consolidation.

  20. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    PubMed

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery. PMID:23002940

  1. TRANSFER EFFECTS IN TASK-SET COST AND DUAL-TASK COST AFTER DUAL-TASK TRAINING IN OLDER AND YOUNGER ADULTS: FURTHER EVIDENCE FOR COGNITIVE PLASTICITY IN ATTENTIONAL CONTROL IN LATE ADULTHOOD

    PubMed Central

    Bherer, Louis; Kramer, Arthur F.; Peterson, Matthew S.; Colcombe, Stanley; Erickson, Kirk; Becic, Ensar

    2010-01-01

    Older adults’ difficulties in performing two tasks concurrently have been well documented (Kramer & Madden, 2008). It has been observed that the age-related differences in dual-task performance are larger when the two tasks require similar motor responses (Hartley, 2001) and that in some conditions older adults also show greater susceptibility than younger adults to input interference (Hein & Schubert, 2004). The authors recently observed that even when the two tasks require motor responses, both older and younger adults can learn to perform a visual discrimination task and an auditory discrimination task faster and more accurately (Bherer et al., 2005). In the present study, the authors extended this finding to a dual-task condition that involves two visual tasks requiring two motor responses. Older and younger adults completed a dual-task training program in which continuous individualized adaptive feedback was provided to enhance performance. The results indicate that, even with similar motor responses and two visual stimuli, both older and younger adults showed substantial gains in performance after training and that the improvement generalized to new task combinations involving new stimuli. These results suggest that dual-task skills can be substantially improved in older adults and that cognitive plasticity in attentional control is still possible in old age. PMID:18568979

  2. Plastics Technology.

    ERIC Educational Resources Information Center

    Barker, Tommy G.

    This curriculum guide is designed to assist junior high schools industrial arts teachers in planning new courses and revising existing courses in plastics technology. Addressed in the individual units of the guide are the following topics: introduction to production technology; history and development of plastics; safety; youth leadership,…

  3. Computational implications of cooperative plasticity induction at nearby dendritic sites.

    PubMed

    Morita, Kenji

    2009-01-01

    Recent studies have revealed that plasticity is not regulated independently at individual synapses but rather that there is cooperativity or associativity between nearby synapses in the dendritic tree of individual cortical pyramidal cells. Here, I summarize experimental results regarding such cooperative plasticity and its underlying mechanisms and consider their computational implications. PMID:19126862

  4. Cortical maturation and myelination in healthy toddlers and young children

    PubMed Central

    Deoni, Sean C.L.; Dean, Douglas C.; Remer, Justin; Dirks, Holly; O’Muircheartaigh, Jonathan

    2015-01-01

    The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6 years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1 year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development. PMID:25944614

  5. Cortical maturation and myelination in healthy toddlers and young children.

    PubMed

    Deoni, Sean C L; Dean, Douglas C; Remer, Justin; Dirks, Holly; O'Muircheartaigh, Jonathan

    2015-07-15

    The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6 years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1 year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development.

  6. Lifespan Differences in Cortical Dynamics of Auditory Perception

    ERIC Educational Resources Information Center

    Muller, Viktor; Gruber, Walter; Klimesch, Wolfgang; Lindenberger, Ulman

    2009-01-01

    Using electroencephalographic recordings (EEG), we assessed differences in oscillatory cortical activity during auditory-oddball performance between children aged 9-13 years, younger adults, and older adults. From childhood to old age, phase synchronization increased within and between electrodes, whereas whole power and evoked power decreased. We…

  7. Meditation experience is associated with increased cortical thickness.

    PubMed

    Lazar, Sara W; Kerr, Catherine E; Wasserman, Rachel H; Gray, Jeremy R; Greve, Douglas N; Treadway, Michael T; McGarvey, Metta; Quinn, Brian T; Dusek, Jeffery A; Benson, Herbert; Rauch, Scott L; Moore, Christopher I; Fischl, Bruce

    2005-11-28

    Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

  8. Cement line staining in undecalcified thin sections of cortical bone

    NASA Technical Reports Server (NTRS)

    Bain, S. D.; Impeduglia, T. M.; Rubin, C. T.

    1990-01-01

    A technique for demonstrating cement lines in thin, undecalcified, transverse sections of cortical bone has been developed. Cortical bone samples are processed and embedded undecalcified in methyl methacrylate plastic. After sectioning at 3-5 microns, cross-sections are transferred to a glass slide and flattened for 10 min. Sections of cortical bone are stained for 20 sec free-floating in a fresh solution of 1% toluidine blue dissolved in 0.1% formic acid. The section is dehydrated in t-butyl alcohol, cleared in xylene, and mounted with Eukitt's medium. Reversal lines appear as thin, scalloped, dark blue lines against a light blue matrix, whereas bone formation arrest lines are thicker with a smooth contour. With this technique cellular detail, osteoid differentiation, and fluorochrome labels are retained. Results demonstrate the applicability of a one-step staining method for cement lines which will facilitate the assessment of bone remodeling activity in thin sections of undecalcified cortical bone.

  9. Auditory map plasticity: Diversity in causes and consequences

    PubMed Central

    Schreiner, Christoph E.; Polley, Daniel B.

    2014-01-01

    Auditory cortical maps have been a long-standing focus of studies that assess the expression, mechanisms, and consequences of sensory plasticity. Here we discuss recent progress in understanding how auditory experience transforms spatially organized sound representations at higher levels of the central auditory pathways. New insights into the mechanisms underlying map changes have been achieved and more refined interpretations of various map plasticity effects and their consequences in terms of behavioral corollaries and learning as well as other cognitive aspects have been offered. The systematic organizational principles of cortical sound processing remains a key-aspect in studying and interpreting the role of plasticity in hearing. PMID:24492090

  10. Massive cortical reorganization in sighted Braille readers.

    PubMed

    Siuda-Krzywicka, Katarzyna; Bola, Łukasz; Paplińska, Małgorzata; Sumera, Ewa; Jednoróg, Katarzyna; Marchewka, Artur; Śliwińska, Magdalena W; Amedi, Amir; Szwed, Marcin

    2016-03-15

    The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills.

  11. Massive cortical reorganization in sighted Braille readers.

    PubMed

    Siuda-Krzywicka, Katarzyna; Bola, Łukasz; Paplińska, Małgorzata; Sumera, Ewa; Jednoróg, Katarzyna; Marchewka, Artur; Śliwińska, Magdalena W; Amedi, Amir; Szwed, Marcin

    2016-01-01

    The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills. PMID:26976813

  12. The Neurophysiologist Perspective into MS Plasticity

    PubMed Central

    Houdayer, Elise; Comi, Giancarlo; Leocani, Letizia

    2015-01-01

    Multiple sclerosis (MS) is a frequent, highly debilitating inflammatory demyelinating disease, starting to manifest in early adulthood and presenting a wide variety of symptoms, which are often resistant to pharmacological treatments. Cortical dysfunctions have been demonstrated to be key components of MS condition, and plasticity of the corticospinal motor system is highly involved in major MS symptoms, such as fatigue, spasticity, or pain. Cortical dysfunction in MS can be studied with neurophysiological tools, such as electroencephalography (EEG) and related techniques (evoked potentials) or transcranial magnetic stimulation (TMS). These techniques are now widely used to provide essential elements of MS diagnosis and can also be used to modulate plasticity. Indeed, the recent development of non-invasive brain stimulation techniques able to induce cortical plasticity, such as repetitive TMS or transcranial direct current stimulation, has brought promising results as add-on treatments. In this review, we will focus on the use of these tools (EEG and TMS) to study plasticity in MS and on the major techniques used to modulate plasticity in MS. PMID:26388835

  13. Cortical State and Attention

    PubMed Central

    Harris, Kenneth D.; Thiele, Alexander

    2012-01-01

    Preface The brain continuously adapts its processing machinery to behavioural demands. To achieve this it rapidly modulates the operating mode of cortical circuits, controlling the way information is transformed and routed. This article will focus on two experimental approaches by which the control of cortical information processing has been investigated: the study of state-dependent cortical processing in rodents, and attention in the primate visual system. Both processes involve a modulation of low-frequency activity fluctuations and spiking correlation, and are mediated by common receptor systems. We suggest that selective attention involves processes similar to state change, operating at a local columnar level to enhance the representation of otherwise nonsalient features while suppressing internally generated activity patterns. PMID:21829219

  14. Repetition suppression for speech processing in the associative occipital and parietal cortex of congenitally blind adults.

    PubMed

    Arnaud, Laureline; Sato, Marc; Ménard, Lucie; Gracco, Vincent L

    2013-01-01

    In the congenitally blind (CB), sensory deprivation results in cross-modal plasticity, with visual cortical activity observed for various auditory tasks. This reorganization has been associated with enhanced auditory abilities and the recruitment of visual brain areas during sound and language processing. The questions we addressed are whether visual cortical activity might also be observed in CB during passive listening to auditory speech and whether cross-modal plasticity is associated with adaptive differences in neuronal populations compared to sighted individuals (SI). We focused on the neural substrate of vowel processing in CB and SI adults using a repetition suppression (RS) paradigm. RS has been associated with enhanced or accelerated neural processing efficiency and synchronous activity between interacting brain regions. We evaluated whether cortical areas in CB were sensitive to RS during repeated vowel processing and whether there were differences across the two groups. In accordance with previous studies, both groups displayed a RS effect in the posterior temporal cortex. In the blind, however, additional occipital, temporal and parietal cortical regions were associated with predictive processing of repeated vowel sounds. The findings suggest a more expanded role for cross-modal compensatory effects in blind persons during sound and speech processing and a functional transfer of specific adaptive properties across neural regions as a consequence of sensory deprivation at birth.

  15. Cortical dynamics revisited.

    PubMed

    Singer, Wolf

    2013-12-01

    Recent discoveries on the organisation of the cortical connectome together with novel data on the dynamics of neuronal interactions require an extension of classical concepts on information processing in the cerebral cortex. These new insights justify considering the brain as a complex, self-organised system with nonlinear dynamics in which principles of distributed, parallel processing coexist with serial operations within highly interconnected networks. The observed dynamics suggest that cortical networks are capable of providing an extremely high-dimensional state space in which a large amount of evolutionary and ontogenetically acquired information can coexist and be accessible to rapid parallel search.

  16. Plasticity of Binocularity and Visual Acuity Are Differentially Limited by Nogo Receptor

    PubMed Central

    Stephany, Céleste-Élise; Chan, Leanne L.H.; Parivash, Sherveen N.; Dorton, Hilary M.; Piechowicz, Mariel

    2014-01-01

    The closure of developmental critical periods consolidates neural circuitry but also limits recovery from early abnormal sensory experience. Degrading vision by one eye throughout a critical period both perturbs ocular dominance (OD) in primary visual cortex and impairs visual acuity permanently. Yet understanding how binocularity and visual acuity interrelate has proven elusive. Here we demonstrate the plasticity of binocularity and acuity are separable and differentially regulated by the neuronal nogo receptor 1 (NgR1). Mice lacking NgR1 display developmental OD plasticity as adults and their visual acuity spontaneously improves after prolonged monocular deprivation. Restricting deletion of NgR1 to either cortical interneurons or a subclass of parvalbumin (PV)-positive interneurons alters intralaminar synaptic connectivity in visual cortex and prevents closure of the critical period for OD plasticity. However, loss of NgR1 in PV neurons does not rescue deficits in acuity induced by chronic visual deprivation. Thus, NgR1 functions with PV interneurons to limit plasticity of binocularity, but its expression is required more extensively within brain circuitry to limit improvement of visual acuity following chronic deprivation. PMID:25164659

  17. Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex.

    PubMed

    Ziemann, Ulf; Ilić, Tihomir V; Iliać, Tihomir V; Pauli, Christian; Meintzschel, Frank; Ruge, Diane

    2004-02-18

    Learning may alter rapidly the output organization of adult motor cortex. It is a long-held hypothesis that modification of synaptic strength along cortical horizontal connections through long-term potentiation (LTP) and long-term depression (LTD) forms one important mechanism for learning-induced cortical plasticity. Strong evidence in favor of this hypothesis was provided for rat primary motor cortex (M1) by showing that motor learning reduced subsequent LTP but increased LTD. Whether a similar relationship exists in humans is unknown. Here, we induced LTP-like and LTD-like plasticity in the intact human M1 by an established paired associative stimulation (PAS) protocol. PAS consisted of 200 pairs of electrical stimulation of the right median nerve, followed by focal transcranial magnetic stimulation of the hand area of the left M1 at an interval equaling the individual N20 latency of the median nerve somatosensory-evoked cortical potential (PAS(N20)) or N20-5 msec (PAS(N20-5)). PAS(N20) induced reproducibly a LTP-like long-lasting (>30 min) increase in motor-evoked potentials from the left M1 to a thumb abductor muscle of the right hand, whereas PAS(N20-5) induced a LTD-like decrease. Repeated fastest possible thumb abduction movements resulted in learning, defined by an increase in maximum peak acceleration of the practiced movements, and prevented subsequent PAS(N20)-induced LTP-like plasticity but enhanced subsequent PAS(N20-5)-induced LTD-like plasticity. The same number of repeated slow thumb abduction movements did not result in learning and had no effects on PAS-induced plasticity. Findings support the view that learning in human M1 occurs through LTP-like mechanisms.

  18. Environmental enrichment rescues the degraded auditory temporal resolution of cortical neurons induced by early noise exposure.

    PubMed

    Jiang, Cuiping; Xu, Xiaoxiao; Yu, Liping; Xu, Jinghong; Zhang, Jiping

    2015-09-01

    The accurate processing of sound temporal information is crucial to human speech perception and other species-specific communication. During postnatal development, the auditory cortex shows environmental and experience-dependent plasticity. However, how the postnatal environment affects cortical processing of sound temporal information is not fully understood. The aim of the present study was to determine whether postnatal noise exposure impairs neural temporal resolution in the auditory cortex, and, if so, whether environmental enrichment can rescue this degraded neural temporal acuity. Using the neural gap detection threshold determined in anesthetized rats as an index of temporal acuity, we found that exposure of juvenile rats to moderate-level noise induced much higher neural gap detection thresholds in adulthood than exposure of adult rats to the same noise. Environmental enrichment did not affect cortical neural gap detection thresholds in normally developing rats. However, rearing of rats with early noise exposure in an enriched environment promoted recovery from the noise-induced degraded neural temporal resolution. In addition, the tonal stimuli in the enriched environment contributed to only a portion of the recovery. These results provide evidence for noise-induced developmental impairment in neural gap detection thresholds in the auditory cortex, and suggest a therapeutic potential for environmental enrichment as a non-invasive approach to rescue developmentally degraded auditory temporal processing.

  19. Environmental acoustic enrichment promotes recovery from developmentally degraded auditory cortical processing.

    PubMed

    Zhu, Xiaoqing; Wang, Fang; Hu, Huifang; Sun, Xinde; Kilgard, Michael P; Merzenich, Michael M; Zhou, Xiaoming

    2014-04-16

    It has previously been shown that environmental enrichment can enhance structural plasticity in the brain and thereby improve cognitive and behavioral function. In this study, we reared developmentally noise-exposed rats in an acoustic-enriched environment for ∼4 weeks to investigate whether or not enrichment could restore developmentally degraded behavioral and neuronal processing of sound frequency. We found that noise-exposed rats had significantly elevated sound frequency discrimination thresholds compared with age-matched naive rats. Environmental acoustic enrichment nearly restored to normal the behavioral deficit resulting from early disrupted acoustic inputs. Signs of both degraded frequency selectivity of neurons as measured by the bandwidth of frequency tuning curves and decreased long-term potentiation of field potentials recorded in the primary auditory cortex of these noise-exposed rats also were reversed partially. The observed behavioral and physiological effects induced by enrichment were accompanied by recovery of cortical expressions of certain NMDA and GABAA receptor subunits and brain-derived neurotrophic factor. These studies in a rodent model show that environmental acoustic enrichment promotes recovery from early noise-induced auditory cortical dysfunction and indicate a therapeutic potential of this noninvasive approach for normalizing neurological function from pathologies that cause hearing and associated language impairments in older children and adults.

  20. Visualization of Cortical Dynamics

    NASA Astrophysics Data System (ADS)

    Grinvald, Amiram

    2003-03-01

    Recent progress in studies of cortical dynamics will be reviewed including the combination of real time optical imaging based on voltage sensitive dyes, single and multi- unit recordings, LFP, intracellular recordings and microstimulation. To image the flow of neuronal activity from one cortical site to the next, in real time, we have used optical imaging based on newly designed voltage sensitive dyes and a Fuji 128x 128 fast camera which we modified. A factor of 20-40 fold improvement in the signal to noise ratio was obtained with the new dye during in vivo imaging experiments. This improvements has facilitates the exploration of cortical dynamics without signal averaging in the millisecond time domain. We confirmed that the voltage sensitive dye signal indeed reflects membrane potential changes in populations of neurons by showing that the time course of the intracellular activity recorded intracellularly from a single neuron was highly correlated in many cases with the optical signal from a small patch of cortex recorded nearby. We showed that the firing of single cortical neurons is not a random process but occurs when the on-going pattern of million of neurons is similar to the functional architecture map which correspond to the tuning properties of that neuron. Chronic optical imaging, combined with electrical recordings and microstimulation, over a long period of times of more than a year, was successfully applied also to the study of higher brain functions in the behaving macaque monkey.

  1. Plastic condoms.

    PubMed

    1968-01-01

    Only simple equipment, simple technology and low initial capital investment are needed in their manufacture. The condoms can be made by people who were previously unskilled or only semi-skilled workers. Plastic condoms differ from those made of latex rubber in that the nature of the plastic film allows unlimited shelf-life. Also, the plastic has a higher degree of lubricity than latex rubber; if there is a demand for extra lubrication in a particular market, this can be provided. Because the plastic is inert, these condoms need not be packaged in hermetically sealed containers. All these attributes make it possible to put these condoms on the distributors' shelves in developing countries competitively with rubber condoms. The shape of the plastic condom is based on that of the lamb caecum, which has long been used as luxury-type condom. The plastic condom is made from plastic film (ethylene ethyl acrilate) of 0.001 inch (0.0254 mm.) thickness. In addition, a rubber ring is provided and sealed into the base of the condom for retention during coitus. The advantage of the plastic condom design and the equipment on which it is made is that production can be carried out either in labour-intensive economy or with varying degrees of mechanization and automation. The uniform, finished condom if made using previously untrained workers. Training of workers can be done in a matter of hours on the two machines which are needed to produce and test the condoms. The plastic film is provided on a double wound roll, and condom blanks are prepared by means of a heat-sealing die on the stamping machine. The rubber rings are united to the condom blanks on an assembly machine, which consists of a mandrel and heat-sealing equipment to seal the rubber ring to the base of the condom. Built into the assembly machine is a simple air-testing apparatus that can detect the smallest pinhole flaw in a condom. The manufacturing process is completed by unravelling the condom from the assembly

  2. The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices.

    PubMed

    Krause, T; Asseyer, S; Taskin, B; Flöel, A; Witte, A V; Mueller, K; Fiebach, J B; Villringer, K; Villringer, A; Jungehulsing, G J

    2016-01-01

    It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed.

  3. Developmental cortical thinning in fetal alcohol spectrum disorders.

    PubMed

    Zhou, Dongming; Lebel, Catherine; Lepage, Claude; Rasmussen, Carmen; Evans, Alan; Wyper, Katy; Pei, Jacqueline; Andrew, Gail; Massey, Ashleigh; Massey, Donald; Beaulieu, Christian

    2011-09-01

    Regional cortical thickness was evaluated using CIVET processing of 3D T1-weighted images (i) to compare the variation in cortical thickness between 33 participants with fetal alcohol spectrum disorders (FASD) aged 6-30 years (mean age 12.3 years) versus 33 age/sex/hand-matched controls, and (ii) to examine developmental changes in cortical thickness with age from children to young adults in both groups. Significant cortical thinning was found in the participants with FASD in large areas of the bilateral middle frontal lobe, pre- and post- central areas, lateral and inferior temporal and occipital lobes compared to controls. No significant cortical thickness increases were observed for the FASD group. Cortical thinning with age in a linear model was observed in both groups, but the locations were different for each group. FASD participants showed thinning with age in the left middle frontal, bilateral precentral, bilateral precuneus and paracingulate, left inferior occipital and bilateral fusiform gyri; while controls showed decreases with age in the bilateral middle frontal gyrus, right inferior frontal gyrus, bilateral precuneus gyrus, and bilateral occipital gyrus. A battery of cognitive assessments of memory, attention, motor, and verbal abilities was conducted with many of the FASD participants, but no significant correlations were found between these cognitive scores and regional cortical thickness. Non-invasive measurements of cortical thickness in children to young adults with FASD have identified both key regions of cortex that may be more deleteriously affected by prenatal alcohol exposure as well as cortical changes with age that differ from normal developmental thinning.

  4. Early depolarizing GABA controls critical period plasticity in the rat visual cortex

    PubMed Central

    Deidda, Gabriele; Allegra, Manuela; Cerri, Chiara; Naskar, Shovan; Bony, Guillaume; Zunino, Giulia; Bozzi, Yuri; Caleo, Matteo; Cancedda, Laura

    2014-01-01

    SUMMARY Hyperpolarizing and inhibitory GABA regulates “critical periods” for plasticity in sensory cortices. Here, we examine the role of early, depolarizing GABA in controlling plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical period plasticity in visual cortical circuits, without affecting overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, down-regulation of BDNF expression, and reduced density of extracellular matrix-perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long-lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF. PMID:25485756

  5. Synapse-Centric Mapping of Cortical Models to the SpiNNaker Neuromorphic Architecture.

    PubMed

    Knight, James C; Furber, Steve B

    2016-01-01

    While the adult human brain has approximately 8.8 × 10(10) neurons, this number is dwarfed by its 1 × 10(15) synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows 4× more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously.

  6. Synapse-Centric Mapping of Cortical Models to the SpiNNaker Neuromorphic Architecture

    PubMed Central

    Knight, James C.; Furber, Steve B.

    2016-01-01

    While the adult human brain has approximately 8.8 × 1010 neurons, this number is dwarfed by its 1 × 1015 synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows 4× more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously.

  7. Synapse-Centric Mapping of Cortical Models to the SpiNNaker Neuromorphic Architecture.

    PubMed

    Knight, James C; Furber, Steve B

    2016-01-01

    While the adult human brain has approximately 8.8 × 10(10) neurons, this number is dwarfed by its 1 × 10(15) synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows 4× more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously. PMID:27683540

  8. Synapse-Centric Mapping of Cortical Models to the SpiNNaker Neuromorphic Architecture

    PubMed Central

    Knight, James C.; Furber, Steve B.

    2016-01-01

    While the adult human brain has approximately 8.8 × 1010 neurons, this number is dwarfed by its 1 × 1015 synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows 4× more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously. PMID:27683540

  9. Acute Stress, But not Corticosterone, Disrupts Short- and Long-Term Synaptic Plasticity in Rat Dorsal Subiculum Via Glucocorticoid Receptor Activation

    PubMed Central

    MacDougall, Matthew J.; Howland, John G.

    2015-01-01

    The subiculum (SUB) serves as the major output structure of the hippocampus; therefore, exploring synaptic plasticity within this region is of great importance for understanding the dynamics of hippocampal circuitry and hippocampal–cortical interactions. Previous research has shown exposure to acute stress dramatically alters synaptic plasticity within the hippocampus proper. Using in vivo electrophysiological recordings in urethane-anesthetized adult male Sprague–Dawley rats, we tested the effects of either acute restraint stress (30 min) or corticosterone (CORT) injections (3 mg/kg; s.c.) on short- and long-term forms of synaptic plasticity in the Cornu Ammonis 1–SUB pathway. Paired-pulse facilitation and two forms of long-term plasticity (long-term potentiation and late-developing potentiation) were significantly reduced after exposure to acute stress but not CORT treatment. Measurements of plasma CORT confirmed similar levels of circulating hormone in animals exposed to either acute stress or CORT treatment. The disruptive effects of acute stress on both short- and long-term forms of synaptic plasticity are mediated by glucocorticoid receptor (GR) activation as these disruptions were blocked by pre-treatment with the selective GR antagonist RU38486 (10 mg/kg; s.c.). The present results highlight the susceptibility of subicular plasticity to acute stress and provide evidence that GR activation is necessary but not sufficient for mediating these alterations. PMID:22918985

  10. Emergence of a Stable Cortical Map for Neuroprosthetic Control

    PubMed Central

    Ganguly, Karunesh; Carmena, Jose M.

    2009-01-01

    Cortical control of neuroprosthetic devices is known to require neuronal adaptations. It remains unclear whether a stable cortical representation for prosthetic function can be stored and recalled in a manner that mimics our natural recall of motor skills. Especially in light of the mixed evidence for a stationary neuron-behavior relationship in cortical motor areas, understanding this relationship during long-term neuroprosthetic control can elucidate principles of neural plasticity as well as improve prosthetic function. Here, we paired stable recordings from ensembles of primary motor cortex neurons in macaque monkeys with a constant decoder that transforms neural activity to prosthetic movements. Proficient control was closely linked to the emergence of a surprisingly stable pattern of ensemble activity, indicating that the motor cortex can consolidate a neural representation for prosthetic control in the presence of a constant decoder. The importance of such a cortical map was evident in that small perturbations to either the size of the neural ensemble or to the decoder could reversibly disrupt function. Moreover, once a cortical map became consolidated, a second map could be learned and stored. Thus, long-term use of a neuroprosthetic device is associated with the formation of a cortical map for prosthetic function that is stable across time, readily recalled, resistant to interference, and resembles a putative memory engram. PMID:19621062

  11. Assessing cortical network properties using TMS-EEG.

    PubMed

    Rogasch, Nigel C; Fitzgerald, Paul B

    2013-07-01

    The past decade has seen significant developments in the concurrent use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to directly assess cortical network properties such as excitability and connectivity in humans. New hardware solutions, improved EEG amplifier technology, and advanced data processing techniques have allowed substantial reduction of the TMS-induced artifact, which had previously rendered concurrent TMS-EEG impossible. Various physiological artifacts resulting from TMS have also been identified, and methods are being developed to either minimize or remove these sources of artifact. With these developments, TMS-EEG has unlocked regions of the cortex to researchers that were previously inaccessible to TMS. By recording the TMS-evoked response directly from the cortex, TMS-EEG provides information on the excitability, effective connectivity, and oscillatory tuning of a given cortical area, removing the need to infer such measurements from indirect measures. In the following review, we investigate the different online and offline methods for reducing artifacts in TMS-EEG recordings and the physiological information contained within the TMS-evoked cortical response. We then address the use of TMS-EEG to assess different cortical mechanisms such as cortical inhibition and neural plasticity, before briefly reviewing studies that have utilized TMS-EEG to explore cortical network properties at rest and during different functional brain states.

  12. Cortical entrainment to music and its modulation by expertise.

    PubMed

    Doelling, Keith B; Poeppel, David

    2015-11-10

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta-theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.

  13. Cortical entrainment to music and its modulation by expertise.

    PubMed

    Doelling, Keith B; Poeppel, David

    2015-11-10

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta-theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition. PMID:26504238

  14. Cortical entrainment to music and its modulation by expertise

    PubMed Central

    Doelling, Keith B.; Poeppel, David

    2015-01-01

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (<8 Hz; delta–theta) oscillations, similarly entrain to music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15–30 Hz)—often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition. PMID:26504238

  15. Cosmetic Plastic Surgery Statistics

    MedlinePlus

    2014 Cosmetic Plastic Surgery Statistics Cosmetic Procedure Trends 2014 Plastic Surgery Statistics Report Please credit the AMERICAN SOCIETY OF PLASTIC SURGEONS when citing statistical data or using ...

  16. Plastics Technician.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document contains 16 units to consider for use in a tech prep competency profile for the occupation of plastics technician. All the units listed will not necessarily apply to every situation or tech prep consortium, nor will all the competencies within each unit be appropriate. Several units appear within each specific occupation and would…

  17. Learning strategy refinement reverses early sensory cortical map expansion but not behavior: Support for a theory of directed cortical substrates of learning and memory.

    PubMed

    Elias, Gabriel A; Bieszczad, Kasia M; Weinberger, Norman M

    2015-12-01

    Primary sensory cortical fields develop highly specific associative representational plasticity, notably enlarged area of representation of reinforced signal stimuli within their topographic maps. However, overtraining subjects after they have solved an instrumental task can reduce or eliminate the expansion while the successful behavior remains. As the development of this plasticity depends on the learning strategy used to solve a task, we asked whether the loss of expansion is due to the strategy used during overtraining. Adult male rats were trained in a three-tone auditory discrimination task to bar-press to the CS+ for water reward and refrain from doing so during the CS- tones and silent intertrial intervals; errors were punished by a flashing light and time-out penalty. Groups acquired this task to a criterion within seven training sessions by relying on a strategy that was "bar-press from tone-onset-to-error signal" ("TOTE"). Three groups then received different levels of overtraining: Group ST, none; Group RT, one week; Group OT, three weeks. Post-training mapping of their primary auditory fields (A1) showed that Groups ST and RT had developed significantly expanded representational areas, specifically restricted to the frequency band of the CS+ tone. In contrast, the A1 of Group OT was no different from naïve controls. Analysis of learning strategy revealed this group had shifted strategy to a refinement of TOTE in which they self-terminated bar-presses before making an error ("iTOTE"). Across all animals, the greater the use of iTOTE, the smaller was the representation of the CS+ in A1. Thus, the loss of cortical expansion is attributable to a shift or refinement in strategy. This reversal of expansion was considered in light of a novel theoretical framework (CONCERTO) highlighting four basic principles of brain function that resolve anomalous findings and explaining why even a minor change in strategy would involve concomitant shifts of involved brain

  18. Learning strategy refinement reverses early sensory cortical map expansion but not behavior: Support for a theory of directed cortical substrates of learning and memory.

    PubMed

    Elias, Gabriel A; Bieszczad, Kasia M; Weinberger, Norman M

    2015-12-01

    Primary sensory cortical fields develop highly specific associative representational plasticity, notably enlarged area of representation of reinforced signal stimuli within their topographic maps. However, overtraining subjects after they have solved an instrumental task can reduce or eliminate the expansion while the successful behavior remains. As the development of this plasticity depends on the learning strategy used to solve a task, we asked whether the loss of expansion is due to the strategy used during overtraining. Adult male rats were trained in a three-tone auditory discrimination task to bar-press to the CS+ for water reward and refrain from doing so during the CS- tones and silent intertrial intervals; errors were punished by a flashing light and time-out penalty. Groups acquired this task to a criterion within seven training sessions by relying on a strategy that was "bar-press from tone-onset-to-error signal" ("TOTE"). Three groups then received different levels of overtraining: Group ST, none; Group RT, one week; Group OT, three weeks. Post-training mapping of their primary auditory fields (A1) showed that Groups ST and RT had developed significantly expanded representational areas, specifically restricted to the frequency band of the CS+ tone. In contrast, the A1 of Group OT was no different from naïve controls. Analysis of learning strategy revealed this group had shifted strategy to a refinement of TOTE in which they self-terminated bar-presses before making an error ("iTOTE"). Across all animals, the greater the use of iTOTE, the smaller was the representation of the CS+ in A1. Thus, the loss of cortical expansion is attributable to a shift or refinement in strategy. This reversal of expansion was considered in light of a novel theoretical framework (CONCERTO) highlighting four basic principles of brain function that resolve anomalous findings and explaining why even a minor change in strategy would involve concomitant shifts of involved brain

  19. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    SciTech Connect

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Takeyoshi, Masahiro; Imatanaka, Nobuya; Itahashi, Megu; Murakami, Tomoaki; Shibutani, Makoto

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc{sup +} neurons at 1000 ppm and Fos{sup +} neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues

  20. [In vivo investigation of human brain networks by using cortico-cortical evoked potentials].

    PubMed

    Matsumoto, Riki; Kunieda, Takeharu; Ikeda, Akio

    2012-09-01

    A better understanding of seizure networks and the mechanisms underlying human higher cortical functions requires a detailed knowledge of neuronal connectivity. As it relates to higher cortical functions, such as language, in humans, studies performed in nonhuman primates are less relevant. By using subdural electrodes implanted for presurgical evaluation, we developed an in vivo electrical tract-tracing technique of cortico-cortical evoked potentials (CCEPs). Cortico-cortical connections could be traced by applying repetitive single-pulse electrical stimuli to a part of the cortices and recording evoked cortical potentials from adjacent and remote cortical regions by averaging electrocorticogram time-locked to stimulus onset. This technique has contributed to the understanding of human cortico-cortical networks involved in higher brain functions, such as language, praxis, and higher motor control. Establishing a CCEP connectivity map in the MNI standard space is also of academic importance, since a standardized CCEP connectivity map would provide a substantial reference for noninvasive network analyses. In addition to its importance in basic systems neuroscience, this method, in combination with conventional cortical mapping, could be used to clinically map functional brain systems by tracking cortico-cortical connections among functional cortical regions in individual patients. This approach may help identify the cortico-cortical network of a given function within the context of pathology and any resultant plasticity of brain systems. In relation to epileptogenicity, as CCEPs can be used as a measure of regional cortical excitability, stimulating the epileptic focus and recording CCEPs in adjacent areas could help evaluate cortical excitability at and around the focus.

  1. Cortical entrainment of human hypoglossal motor unit activities

    PubMed Central

    Laine, Christopher M.; Nickerson, Laura A.

    2012-01-01

    Output from the primary motor cortex contains oscillations that can have frequency-specific effects on the firing of motoneurons (MNs). Whereas much is known about the effects of oscillatory cortical drive on the output of spinal MN pools, considerably less is known about the effects on cranial motor nuclei, which govern speech/oromotor control. Here, we investigated cortical input to one such motor pool, the hypoglossal motor nucleus (HMN), which controls muscles of the tongue. We recorded intramuscular genioglossus electromyogram (EMG) and scalp EEG from healthy adult subjects performing a tongue protrusion task. Cortical entrainment of HMN population activity was assessed by measuring coherence between EEG and multiunit EMG activity. In addition, cortical entrainment of individual MN firing activity was assessed by measuring phase locking between single motor unit (SMU) action potentials and EEG oscillations. We found that cortical entrainment of multiunit activity was detectable within the 15- to 40-Hz frequency range but was inconsistent across recordings. By comparison, cortical entrainment of SMU spike timing was reliable within the same frequency range. Furthermore, this effect was found to be intermittent over time. Our study represents an important step in understanding corticomuscular synchronization in the context of human oromotor control and is the first study to document SMU entrainment by cortical oscillations in vivo. PMID:22049332

  2. Cortical control of anticipatory postural adjustments prior to stepping.

    PubMed

    Varghese, J P; Merino, D M; Beyer, K B; McIlroy, W E

    2016-01-28

    Human bipedal balance control is achieved either reactively or predictively by a distributed network of neural areas within the central nervous system with a potential role for cerebral cortex. While the role of the cortex in reactive balance has been widely explored, only few studies have addressed the cortical activations related to predictive balance control. The present study investigated the cortical activations related to the preparation and execution of anticipatory postural adjustment (APA) that precede a step. This study also examined whether the preparatory cortical activations related to a specific movement is dependent on the context of control (postural component vs. focal component). Ground reaction forces and electroencephalographic (EEG) data were recorded from 14 healthy adults while they performed lateral weight shift and lateral stepping with and without initially preloading their weight to the stance leg. EEG analysis revealed that there were distinct movement-related potentials (MRPs) with concurrent event-related desynchronization (ERD) of mu and beta rhythms prior to the onset of APA and also to the onset of foot-off during lateral stepping in the fronto-central cortical areas. Also, the MRPs and ERD prior to the onset of APA and onset of lateral weight shift were not significantly different suggesting the comparable cortical activations for the generation of postural and focal movements. The present study reveals the occurrence of cortical activation prior to the execution of an APA that precedes a step. Importantly, this cortical activity appears independent of the context of the movement. PMID:26608123

  3. Dynamics of Ionic Shifts in Cortical Spreading Depression

    PubMed Central

    Enger, Rune; Tang, Wannan; Vindedal, Gry Fluge; Jensen, Vidar; Johannes Helm, P.; Sprengel, Rolf; Looger, Loren L.; Nagelhus, Erlend A.

    2015-01-01

    Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity. Accumulating evidence indicates that cortical spreading depression underlies the migraine aura and that similar waves promote tissue damage in stroke, trauma, and hemorrhage. Cortical spreading depression is characterized by neuronal swelling, profound elevation of extracellular potassium and glutamate, multiphasic blood flow changes, and drop in tissue oxygen tension. The slow speed of the cortical spreading depression wave implies that it is mediated by diffusion of a chemical substance, yet the identity of this substance and the pathway it follows are unknown. Intercellular spread between gap junction-coupled neurons or glial cells and interstitial diffusion of K+ or glutamate have been proposed. Here we use extracellular direct current potential recordings, K+-sensitive microelectrodes, and 2-photon imaging with ultrasensitive Ca2+ and glutamate fluorescent probes to elucidate the spatiotemporal dynamics of ionic shifts associated with the propagation of cortical spreading depression in the visual cortex of adult living mice. Our data argue against intercellular spread of Ca2+ carrying the cortical spreading depression wavefront and are in favor of interstitial K+ diffusion, rather than glutamate diffusion, as the leading event in cortical spreading depression. PMID:25840424

  4. Purely Cortical Anaplastic Ependymoma

    PubMed Central

    Romero, Flávio Ramalho; Zanini, Marco Antônio; Ducati, Luis Gustavo; Vital, Roberto Bezerra; de Lima Neto, Newton Moreira; Gabarra, Roberto Colichio

    2012-01-01

    Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. It may occur outside the ventricular structures, representing the extraventicular form, or without any relationship of ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic ependymomas were reported and less than five were anaplastic. We report a rare case of pure cortical ectopic anaplastic ependymoma. PMID:23119204

  5. Purely cortical anaplastic ependymoma.

    PubMed

    Romero, Flávio Ramalho; Zanini, Marco Antônio; Ducati, Luis Gustavo; Vital, Roberto Bezerra; de Lima Neto, Newton Moreira; Gabarra, Roberto Colichio

    2012-01-01

    Ependymomas are glial tumors derived from ependymal cells lining the ventricles and the central canal of the spinal cord. It may occur outside the ventricular structures, representing the extraventicular form, or without any relationship of ventricular system, called ectopic ependymona. Less than fifteen cases of ectopic ependymomas were reported and less than five were anaplastic. We report a rare case of pure cortical ectopic anaplastic ependymoma.

  6. Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J; Lehmann, Manja; Schott, Jonathan M; Rabinovici, Gil D; Rossor, Martin N; Fox, Nick C

    2013-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterized by a progressive decline in visuospatial, visuoperceptual, literacy and praxic skills. The progressive neurodegeneration affecting parietal, occipital and occipito-temporal cortices which underlies PCA is attributable to Alzheimer's disease (AD) in the majority of patients. However, alternative underlying aetiologies including Dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and prion disease have also been identified, and not all PCA patients have atrophy on clinical imaging. This heterogeneity has led to diagnostic and terminological inconsistencies, caused difficulty comparing studies from different centres, and limited the generalizability of clinical trials and investigations of factors driving phenotypic variability. Significant challenges remain in identifying the factors associated with both the selective vulnerability of posterior cortical regions and the young age of onset seen in PCA. Greater awareness of the syndrome and agreement over the correspondence between syndrome-and disease-level classifications are required in order to improve diagnostic accuracy, research study design and clinical management. PMID:22265212

  7. Consistent cortical reconstruction and multi-atlas brain segmentation.

    PubMed

    Huo, Yuankai; Plassard, Andrew J; Carass, Aaron; Resnick, Susan M; Pham, Dzung L; Prince, Jerry L; Landman, Bennett A

    2016-09-01

    Whole brain segmentation and cortical surface reconstruction are two essential techniques for investigating the human brain. Spatial inconsistences, which can hinder further integrated analyses of brain structure, can result due to these two tasks typically being conducted independently of each other. FreeSurfer obtains self-consistent whole brain segmentations and cortical surfaces. It starts with subcortical segmentation, then carries out cortical surface reconstruction, and ends with cortical segmentation and labeling. However, this "segmentation to surface to parcellation" strategy has shown limitations in various cohorts such as older populations with large ventricles. In this work, we propose a novel "multi-atlas segmentation to surface" method called Multi-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. A modification called MaCRUISE(+) is designed to perform well when white matter lesions are present. Comparing to the benchmarks CRUISE and FreeSurfer, the surface accuracy of MaCRUISE and MaCRUISE(+) is validated using two independent datasets with expertly placed cortical landmarks. A third independent dataset with expertly delineated volumetric labels is employed to compare segmentation performance. Finally, 200MR volumetric images from an older adult sample are used to assess the robustness of MaCRUISE and FreeSurfer. The advantages of MaCRUISE are: (1) MaCRUISE constructs self-consistent voxelwise segmentations and cortical surfaces, while MaCRUISE(+) is robust to white matter pathology. (2) MaCRUISE achieves more accurate whole brain segmentations than independently conducting the multi-atlas segmentation. (3) MaCRUISE is comparable in accuracy to FreeSurfer (when FreeSurfer does not exhibit global failures) while achieving greater robustness across an older adult population. MaCRUISE has been made freely

  8. Consistent cortical reconstruction and multi-atlas brain segmentation.

    PubMed

    Huo, Yuankai; Plassard, Andrew J; Carass, Aaron; Resnick, Susan M; Pham, Dzung L; Prince, Jerry L; Landman, Bennett A

    2016-09-01

    Whole brain segmentation and cortical surface reconstruction are two essential techniques for investigating the human brain. Spatial inconsistences, which can hinder further integrated analyses of brain structure, can result due to these two tasks typically being conducted independently of each other. FreeSurfer obtains self-consistent whole brain segmentations and cortical surfaces. It starts with subcortical segmentation, then carries out cortical surface reconstruction, and ends with cortical segmentation and labeling. However, this "segmentation to surface to parcellation" strategy has shown limitations in various cohorts such as older populations with large ventricles. In this work, we propose a novel "multi-atlas segmentation to surface" method called Multi-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. A modification called MaCRUISE(+) is designed to perform well when white matter lesions are present. Comparing to the benchmarks CRUISE and FreeSurfer, the surface accuracy of MaCRUISE and MaCRUISE(+) is validated using two independent datasets with expertly placed cortical landmarks. A third independent dataset with expertly delineated volumetric labels is employed to compare segmentation performance. Finally, 200MR volumetric images from an older adult sample are used to assess the robustness of MaCRUISE and FreeSurfer. The advantages of MaCRUISE are: (1) MaCRUISE constructs self-consistent voxelwise segmentations and cortical surfaces, while MaCRUISE(+) is robust to white matter pathology. (2) MaCRUISE achieves more accurate whole brain segmentations than independently conducting the multi-atlas segmentation. (3) MaCRUISE is comparable in accuracy to FreeSurfer (when FreeSurfer does not exhibit global failures) while achieving greater robustness across an older adult population. MaCRUISE has been made freely

  9. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord.

    PubMed

    Karimi-Abdolrezaee, Soheila; Eftekharpour, Eftekhar; Wang, Jian; Schut, Desiree; Fehlings, Michael G

    2010-02-01

    The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for spinal cord injury (SCI). However, to date NPC transplantation has exhibited only limited success in the treatment of chronic SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial scar around the site of chronic SCI negatively influence the long-term survival and integration of transplanted NPCs and their therapeutic potential for promoting functional repair and plasticity. We targeted CSPGs in the chronically injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week later, the same rats were treated with transplants of NPCs and transient infusion of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs successfully integrate and extensively migrate within the host spinal cord and principally differentiate into oligodendrocytes. Furthermore, this combined strategy promoted the axonal integrity and plasticity of the corticospinal tract and enhanced the plasticity of descending serotonergic pathways. These neuroanatomical changes were also associated with significantly improved neurobehavioral recovery after chronic SCI. Importantly, this strategy did not enhance the aberrant synaptic connectivity of pain afferents, nor did it exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key biological and functional benefits for the combined use of ChABC, growth factors, and NPCs to repair the chronically injured spinal cord. These findings could potentially bring us closer to the application of NPCs for patients suffering from chronic SCI or other conditions characterized by the formation of a glial scar.

  10. Plastic bronchitis.

    PubMed

    Singhi, Anil Kumar; Vinoth, Bharathi; Kuruvilla, Sarah; Sivakumar, Kothandam

    2015-01-01

    Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its current understanding. PMID:26556975

  11. Learning New Names for New Objects: Cortical Effects as Measured by Magnetoencephalography

    ERIC Educational Resources Information Center

    Cornelissen, Katri; Laine, Matti; Renvall, Kati; Saarinen, Timo; Martin, Nadine; Salmelin, Riitta

    2004-01-01

    We tracked the evolvement of naming-related cortical dynamics with magnetoencephalography when five normal adults successfully learned names and/or meanings of unfamiliar objects. In all subjects, the learning of new names was associated with pronounced cortical effects. The learning effect was of long latency and emerged as a change of activation…

  12. Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients with Childhood-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

    2011-01-01

    Objective: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to…

  13. Cortical excitability changes following grasping exercise augmented with electrical stimulation.

    PubMed

    Barsi, Gergely I; Popovic, Dejan B; Tarkka, Ina M; Sinkjaer, Thomas; Grey, Michael J

    2008-10-01

    Rehabilitation with augmented electrical stimulation can enhance functional recovery after stroke, and cortical plasticity may play a role in this process. The purpose of this study was to compare the effects of three training paradigms on cortical excitability in healthy subjects. Cortical excitability was evaluated by analysing the input-output relationship between transcranial magnetic stimulation intensity and motor evoked potentials (MEPs) from the flexor muscles of the fingers. The study was performed with 25 healthy volunteers who underwent 20-min simulated therapy sessions of: (1) functional electrical stimulation (FES) of the finger flexors and extensors, (2) voluntary movement (VOL) with sensory stimulation, and (3) therapeutic FES (TFES) where the electrical stimulation augmented voluntary activation. TFES training produced a significant increase in MEP magnitude throughout the stimulation range, suggesting an increase in cortical excitability. In contrast, neither the FES nor voluntary movement alone had such an effect. These results suggest that the combination of voluntary effort and FES has greater potential to induce plasticity in the motor cortex and that TFES might be a more effective approach in rehabilitation after stroke than FES or repetitive voluntary training alone.

  14. Invasive Cortical Stimulation to Promote Recovery of Function After Stroke

    PubMed Central

    Plow, Ela B.; Carey, James R.; Nudo, Randolph J.; Pascual-Leone, Alvaro

    2011-01-01

    Background and Purpose Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result. Summary of Review Regarding cortical stimulation, it is important to determine the