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Sample records for ganglia shape abnormalities

  1. Basal Ganglia Shapes Predict Social, Communication, and Motor Dysfunctions in Boys with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Qiu, Anqi; Adler, Marcy; Crocetti, Deana; Miller, Michael I.; Mostofsky, Stewart H.

    2010-01-01

    Objective: Basal ganglia abnormalities have been suggested as contributing to motor, social, and communicative impairments in autism spectrum disorder (ASD). Volumetric analyses offer limited ability to detect localized differences in basal ganglia structure. Our objective was to investigate basal ganglia shape abnormalities and their association…

  2. Basal Ganglia Shapes Predict Social, Communication, and Motor Dysfunctions in Boys with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Qiu, Anqi; Adler, Marcy; Crocetti, Deana; Miller, Michael I.; Mostofsky, Stewart H.

    2010-01-01

    Objective: Basal ganglia abnormalities have been suggested as contributing to motor, social, and communicative impairments in autism spectrum disorder (ASD). Volumetric analyses offer limited ability to detect localized differences in basal ganglia structure. Our objective was to investigate basal ganglia shape abnormalities and their association…

  3. Tooth - abnormal shape

    MedlinePLUS

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  4. Role of movement in long-term basal ganglia changes: implications for abnormal motor responses

    PubMed Central

    Simola, Nicola; Morelli, Micaela; Frazzitta, Giuseppe; Frau, Lucia

    2013-01-01

    Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson’s disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management. PMID:24167489

  5. Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1?/? Mice

    PubMed Central

    Lim, Soo-Yeon; Mah, Won

    2015-01-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2–3 months old) and juvenile (4 weeks old) Git1?/? mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in Git1?/? mice. PMID:25997734

  6. Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1(-/-) Mice.

    PubMed

    Lim, Soo-Yeon; Mah, Won

    2015-06-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2-3 months old) and juvenile (4 weeks old) Git1(-/-) mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in Git1(-/-) mice. PMID:25997734

  7. Sperm shape abnormalities in carbaryl-exposed employees.

    PubMed

    Wyrobek, A J; Watchmaker, G; Gordon, L; Wong, K; Moore, D; Whorton, D

    1981-08-01

    Semen was collected from 50 men occupationally exposed to carbaryl (1-naphthyl methyl carbamate) in a produciton plant for durations of 1 to 18 years and compared to semen from a control group of 34 unexposed, newly-hired workers. Employment, fertility, health, personal data, and blood samples were collected for each individual. Semen samples were analyzed for changes in sperm count, morphology, and frequency of sperm carrying double flourescent bodies (YFF). As a group, the exposed workers showed a significantly higher proportion of sperm with abnormal head shapes than did the control group (p < 0.005). Age, smoking habits, and medical problems did not appear to affect this result. This finding appears to be limited to men working in the carbaryl production area at the time of sampling. Sperm count and YFF did not show similar differences, which may be because they are known to be statistically less sensitive to small changes. Formerly exposed workers (away from carbaryl for an average of 6.3 years) showed a marginally significant elevation in sperm abnormalities compared to controls (p < .05, one-tailed statistical analyses) suggesting that the increase in abnormal morphology may not be reversible. However, the question of reversibility is sensitive to confounding factors and small sample sizes and, therefore, requires further study. With these data a definitive link between carbaryl exposure and human seminal defects cannot be established. Although a distinct effect on sperm morphology was seen in the exposed group, the increases in sperm shape abnormalities were not related to exposure dose (estimated by number of years on the job or job classification during the year prior to semen collection). Inexplicably, the increases in sperm abnormalities were seen primarily in currently exposed men who had worked with carbaryl for less than approximately 6 years. These findings suggest the need for further study since other workplace-related factor(s) may be responsible for the elevated sperm abnormalities seen in this study. PMID:6791917

  8. SHAPE OF THE BASAL GANGLIA IN PREADOLESCENT CHILDREN IS ASSOCIATED WITH COGNITIVE PERFORMANCE

    PubMed Central

    Sandman, Curt A.; Head, Kevin; Muftuler, L. Tugan; Su, Lydia; Buss, Claudia; Davis, Elysia Poggi.

    2014-01-01

    Current studies support the belief that high levels of performance and intellectual abilities are associated with increased brain size or volume. With few exceptions, this conclusion is restricted to studies of post-adolescent subjects and to cerebral cortex. There is evidence that “bigger is better” may not pertain to children and further, that there are areas of the brain in which larger structures are associated with cognitive deficits. In 50 preadolescent children (21 girls) a structural survey of the brain (VBM) was conducted to determine and locate areas in which gray matter volume was associated with poor cognitive performance. Only increased gray matter volume in particular areas of the basal ganglia and specifically the putamen were significantly associated with poor performance on tests of memory, response speed and a general marker and subtests of intelligence. Based on the VBM findings, volumetric analysis of basal ganglia structures were performed using FSL/FIRST. However, no significant changes in total volume of putamen or other basal ganglia structures were detected with this analysis. The disagreement between measures of localized gray matter differences and volumetric analysis suggested that there might be local regional deformity rather than widespread volumetric changes of the putamen. Surface analysis with FSL/FIRST demonstrated that bilateral outward deformation of the putamen, but especially the left, was associated with poor performance on several cognitive tests. Expansion of the globus pallidus and caudate nucleus also was associated with poor performance. Moreover a significant association was detected between a reliable test of language-free intelligence and topographically distinct outward and inward deformation of the putamen. Expansion and contraction of the putamen as a predictor of intelligence may explain why this association was not observed with measures of total volume. These results suggest that deformity is a sensitive measure of function, and that distortion of the basal ganglia may be a neurophenotype for risk of developmental impairment. PMID:24844741

  9. Shape of the basal ganglia in preadolescent children is associated with cognitive performance.

    PubMed

    Sandman, Curt A; Head, Kevin; Muftuler, L Tugan; Su, Lydia; Buss, Claudia; Davis, Elysia Poggi

    2014-10-01

    Current studies support the belief that high levels of performance and intellectual abilities are associated with increased brain size or volume. With few exceptions, this conclusion is restricted to studies of post-adolescent subjects and to cerebral cortex. There is evidence that "bigger is better" may not pertain to children and further, that there are areas of the brain in which larger structures are associated with cognitive deficits. In 50 preadolescent children (21 girls) a structural survey of the brain (VBM) was conducted to determine and locate areas in which gray matter volume was associated with poor cognitive performance. Only increased gray matter volume in particular areas of the basal ganglia and specifically the putamen was significantly associated with poor performance on tests of memory, response speed and a general marker and subtests of intelligence. Based on the VBM findings, volumetric analysis of basal ganglia structures was performed using FSL/FIRST. However, no significant changes in total volume of putamen or other basal ganglia structures were detected with this analysis. The disagreement between measures of localized gray matter differences and volumetric analysis suggested that there might be local regional deformity rather than widespread volumetric changes of the putamen. Surface analysis with FSL/FIRST demonstrated that bilateral outward deformation of the putamen, but especially the left, was associated with poor performance on several cognitive tests. Expansion of the globus pallidus and caudate nucleus also was associated with poor performance. Moreover a significant association was detected between a reliable test of language-free intelligence and topographically distinct outward and inward deformation of the putamen. Expansion and contraction of the putamen as a predictor of intelligence may explain why this association was not observed with measures of total volume. These results suggest that deformity is a sensitive measure of function, and that distortion of the basal ganglia may be a neurophenotype for risk of developmental impairment. PMID:24844741

  10. Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

    PubMed Central

    Portmann, Thomas; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L.; Zhengqui, Zhou; Miller, Michael A.; Lerch, Jason P.; Henkelman, Mark; Shamloo, Mehrdad; Malenka, Robert C.; Crawley, Jacqueline N.; Dolmetsch, Ricardo E.

    2014-01-01

    Summary A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/− mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/− mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. PMID:24794428

  11. Stimulation of serotonin2C receptors elicits abnormal oral movements by acting on pathways other than the sensorimotor one in the rat basal ganglia.

    PubMed

    Beyeler, A; Kadiri, N; Navailles, S; Boujema, M Ben; Gonon, F; Moine, C Le; Gross, C; De Deurwaerdère, P

    2010-08-11

    Serotonin2C (5-HT(2C)) receptors act in the basal ganglia, a group of sub-cortical structures involved in motor behavior, where they are thought to modulate oral activity and participate in iatrogenic motor side-effects in Parkinson's disease and Schizophrenia. Whether abnormal movements initiated by 5-HT(2C) receptors are directly consequent to dysfunctions of the motor circuit is uncertain. In the present study, we combined behavioral, immunohistochemical and extracellular single-cell recordings approaches in rats to investigate the effect of the 5-HT(2C) agonist Ro-60-0175 respectively on orofacial dyskinesia, the expression of the marker of neuronal activity c-Fos in basal ganglia and the electrophysiological activity of substantia nigra pars reticulata (SNr) neuron connected to the orofacial motor cortex (OfMC) or the medial prefrontal cortex (mPFC). The results show that Ro-60-0175 (1 mg/kg) caused bouts of orofacial movements that were suppressed by the 5-HT(2C) antagonist SB-243213 (1 mg/kg). Ro-60-0175 (0.3, 1, 3 mg/kg) dose-dependently enhanced Fos expression in the striatum and the nucleus accumbens. At the highest dose, it enhanced Fos expression in the subthalamic nucleus, the SNr and the entopeduncular nucleus but not in the external globus pallidus. However, the effect of Ro-60-0175 was mainly associated with associative/limbic regions of basal ganglia whereas subregions of basal ganglia corresponding to sensorimotor territories were devoid of Fos labeling. Ro-60-0175 (1-3 mg/kg) did not affect the electrophysiological activity of SNr neurons connected to the OfMC nor their excitatory-inhibitory-excitatory responses to the OfMC electrical stimulation. Conversely, Ro-60-0175 (1 mg/kg) enhanced the late excitatory response of SNr neurons evoked by the mPFC electrical stimulation. These results suggest that oral dyskinesia induced by 5-HT(2C) agonists are not restricted to aberrant signalling in the orofacial motor circuit and demonstrate discrete modifications in associative territories. PMID:20447448

  12. The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson's disease.

    PubMed

    Cagnan, Hayriye; Duff, Eugene Paul; Brown, Peter

    2015-06-01

    Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance-related pathological circuit interactions. PMID:25888552

  13. Use of a Novel High-Resolution Magnetic Resonance Neurography Protocol to Detect Abnormal Dorsal Root Ganglia in Sjögren Patients With Neuropathic Pain

    PubMed Central

    Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C.; Carrino, John; Chhabra, Avneesh

    2014-01-01

    Abstract The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional “stocking-and-glove” distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system—the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain. We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients whose neuropathic pain resolved with intravenous immunoglobulin (IVIg) therapy had improvement of MRN DRG abnormalities. We have developed a novel MRN protocol that can detect DRG abnormalities in SS patients with neuropathic pain who do not have markers of peripheral neuropathy. We found that SS patients with MRN DRG abnormalities had statistically significant, increased IENFD on skin biopsy studies, which may suggest a relationship between trophic mediators and neuropathic pain. Given that our literature review has demonstrated that many SS neuropathic pain patients do not have a neuropathy, our findings suggest an important niche for this MRN DRG technique in the evaluation of broader subsets of SS neuropathic pain patients who may not have underlying neuropathies. The improvement of MRN DRG abnormalities in patients with IVIg-induced remission of neuropathic pain suggests that our MRN protocol may be capturing reversible, immune-mediated mechanisms targeting the DRG. PMID:24797167

  14. Hippocampal Shape Abnormalities of Patients with Childhood-Onset Schizophrenia and Their Unaffected Siblings

    ERIC Educational Resources Information Center

    Johnson, Sarah L. M.; Wang, Lei; Alpert, Kathryn I.; Greenstein, Deanna; Clasen, Liv; Lalonde, Francois; Miller, Rachel; Rapoport, Judith; Gogtay, Nitin

    2013-01-01

    Objective: The hippocampus has been implicated in the pathogenesis of schizophrenia, and hippocampal volume deficits have been a consistently reported abnormality, but the subregional specificity of the deficits remains unknown. The authors explored the nature and developmental trajectory of subregional shape abnormalities of the hippocampus in…

  15. Hippocampal Shape Abnormalities of Patients with Childhood-Onset Schizophrenia and Their Unaffected Siblings

    ERIC Educational Resources Information Center

    Johnson, Sarah L. M.; Wang, Lei; Alpert, Kathryn I.; Greenstein, Deanna; Clasen, Liv; Lalonde, Francois; Miller, Rachel; Rapoport, Judith; Gogtay, Nitin

    2013-01-01

    Objective: The hippocampus has been implicated in the pathogenesis of schizophrenia, and hippocampal volume deficits have been a consistently reported abnormality, but the subregional specificity of the deficits remains unknown. The authors explored the nature and developmental trajectory of subregional shape abnormalities of the hippocampus in…

  16. Subcortical shape and volume abnormalities in an elderly HIV+ cohort

    NASA Astrophysics Data System (ADS)

    Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.

    2015-03-01

    Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

  17. CELL ADHESION MOLECULE CADHERIN-6 FUNCTION IN ZEBRAFISH CRANIAL AND LATERAL LINE GANGLIA DEVELOPMENT

    PubMed Central

    Liu, Q.; Dalman, M. R.; Sarmah, S.; Chen, S.; Chen, Y.; Hurlbut, A. K.; Spencer, M. A.; Pancoe, L.; Marrs, J. A.

    2015-01-01

    Cadherins regulate the vertebrate nervous system development. We previously showed that cadherin-6 message (cdh6) was strongly expressed in the majority of the embryonic zebrafish cranial and lateral line ganglia during their development. Here, we present evidence that cdh6 has specific functions during cranial and lateral line ganglia and nerve development. We analyzed the consequences of cdh6 loss-of-function on cranial ganglion and nerve differentiation in zebrafish embryos. Embryos injected with zebrafish cdh6 specific antisense morpholino oligonucleotides (MOs, which suppress gene expression during development; cdh6 morphant embryos) displayed a specific phenotype, including (i) altered shape and reduced development of a subset of the cranial and lateral line ganglia (e.g. the statoacoustic ganglion and vagal ganglion) and (ii) cranial nerves were abnormally formed. This data illustrates an important role for cdh6 in the formation of cranial ganglia and their nerves. PMID:21584906

  18. Striatal shape abnormalities as novel neurodevelopmental endophenotypes in schizophrenia: a longitudinal study.

    PubMed

    Chakravarty, M Mallar; Rapoport, Judith L; Giedd, Jay N; Raznahan, Armin; Shaw, Philip; Collins, D Louis; Lerch, Jason P; Gogtay, Nitin

    2015-04-01

    There are varying, often conflicting, reports with respect to altered striatal volume and morphometry in the major psychoses due to the influences of antipsychotic medications on striatal volume. Thus, disassociating disease effects from those of medication become exceedingly difficult. For the first time, using a longitudinally studied sample of structural magnetic resonance images from patients with childhood onset schizophrenia (COS; neurobiologically contiguous with the adult onset form of schizophrenia), their nonpsychotic siblings (COSSIBs), and novel shape mapping algorithms that are volume independent, we report the familial contribution of striatal morphology in schizophrenia. The results of our volumetric analyses demonstrate age-related increases in overall striatal volumes specific only to COS. However, both COS and COSSIBs showed overlapping shape differences in the striatal head, which normalized in COSSIBs by late adolescence. These results mirror previous studies from our group, demonstrating cortical thickness deficits in COS and COSSIBs as these deficits normalize in COSSIBs in the same age range as our striatal findings. Finally, there is a single region of nonoverlapping outward displacement in the dorsal aspect of the caudate body, potentially indicative of a response to medication. Striatal shape may be considered complimentary to volume as an endophenotype, and, in some cases may provide information that is not detectable using standard volumetric techniques. Our striatal shape findings demonstrate the striking localization of abnormalities in striatal the head. The neuroanatomical localization of these findings suggest the presence of abnormalities in the striatal-prefrontal circuits in schizophrenia and resilience mechanisms in COSSIBs with age dependent normalization. PMID:25504933

  19. Abnormalities of cortical thickness, subcortical shapes, and white matter integrity in subcortical vascular cognitive impairment.

    PubMed

    Thong, Jamie Yu Jin; Du, Jia; Ratnarajah, Nagulan; Dong, Yanhong; Soon, Hock Wei; Saini, Monica; Tan, Ming Zhen; Ta, Anh Tuan; Chen, Christopher; Qiu, Anqi

    2014-05-01

    Subcortical vascular cognitive impairment (sVCI) is caused by lacunar infarcts or extensive and/or diffuse lesions in the white matter that may disrupt the white matter circuitry connecting cortical and subcortical regions and result in the degeneration of neurons in these regions. This study used structural magnetic resonance imaging (MRI) and high angular resolution diffusion imaging (HARDI) techniques to examine cortical thickness, subcortical shapes, and white matter integrity in mild vascular cognitive impairment no dementia (VCIND Mild) and moderate-to-severe VCI (MSVCI). Our study found that compared to controls (n = 25), VCIND Mild (n = 25), and MSVCI (n = 30) showed thinner cortex predominantly in the frontal cortex. The cortex in MSVCI was thinner in the parietal and lateral temporal cortices than that in VCIND Mild. Moreover, compared to controls, VCIND Mild and MSVCI showed smaller shapes (i.e., volume reduction) in the thalamus, putamen, and globus pallidus and ventricular enlargement. Finally, compared to controls, VCIND Mild, and MSVCI showed an increased mean diffusivity in the white matter, while decreased generalized fractional anisotropy was only found in the MSVCI subjects. The major axonal bundles involved in the white matter abnormalities were mainly toward the frontal regions, including the internal capsule/corona radiata, uncinate fasciculus, and anterior section of the inferior fronto-occipital fasciculus, and were anatomically connected to the affected cortical and subcortical structures. Our findings suggest that abnormalities in cortical, subcortical, and white matter morphology in sVCI occur in anatomically connected structures, and that abnormalities progress along a similar trajectory from the mild to moderate and severe conditions. PMID:23861356

  20. The basal ganglia communicate with the cerebellum.

    PubMed

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2010-05-01

    The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically separate and to perform distinct functional operations. We investigated whether there is any direct route for basal ganglia output to influence cerebellar function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence cerebellar function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated functional network. PMID:20404184

  1. Erythrocyte Shape Abnormalities, Membrane Oxidative Damage, and ?-Actin Alterations: An Unrecognized Triad in Classical Autism

    PubMed Central

    Ciccoli, Lucia; De Felice, Claudio; Pecorelli, Alessandra; Belmonte, Giuseppe; Guerranti, Roberto; Cortelazzo, Alessio; Durand, Thierry; Valacchi, Giuseppe; Rossi, Marcello; Hayek, Joussef

    2013-01-01

    Autism spectrum disorders (ASDs) are a complex group of neurodevelopment disorders steadily rising in frequency and treatment refractory, where the search for biological markers is of paramount importance. Although red blood cells (RBCs) membrane lipidomics and rheological variables have been reported to be altered, with some suggestions indicating an increased lipid peroxidation in the erythrocyte membrane, to date no information exists on how the oxidative membrane damage may affect cytoskeletal membrane proteins and, ultimately, RBCs shape in autism. Here, we investigated RBC morphology by scanning electron microscopy in patients with classical autism, that is, the predominant ASDs phenotype (age range: 6–26 years), nonautistic neurodevelopmental disorders (i.e., “positive controls”), and healthy controls (i.e., “negative controls”). A high percentage of altered RBCs shapes, predominantly elliptocytes, was observed in autistic patients, but not in both control groups. The RBCs altered morphology in autistic subjects was related to increased erythrocyte membrane F2-isoprostanes and 4-hydroxynonenal protein adducts. In addition, an oxidative damage of the erythrocyte membrane ?-actin protein was evidenced. Therefore, the combination of erythrocyte shape abnormalities, erythrocyte membrane oxidative damage, and ?-actin alterations constitutes a previously unrecognized triad in classical autism and provides new biological markers in the diagnostic workup of ASDs. PMID:24453417

  2. Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder

    PubMed Central

    Womer, Fay Y.; Wang, Lei; Alpert, Kathryn; Smith, Matthew J.; Csernansky, John G.; Barch, Deanna; Mamah, Daniel

    2014-01-01

    In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing the BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies. PMID:24957866

  3. SPACA1-deficient male mice are infertile with abnormally shaped sperm heads reminiscent of globozoospermia.

    PubMed

    Fujihara, Yoshitaka; Satouh, Yuhkoh; Inoue, Naokazu; Isotani, Ayako; Ikawa, Masahito; Okabe, Masaru

    2012-10-01

    SPACA1 is a membrane protein that localizes in the equatorial segment of spermatozoa in mammals and is reported to function in sperm-egg fusion. We produced a Spaca1 gene-disrupted mouse line and found that the male mice were infertile. The cause of this sterility was abnormal shaping of the sperm head reminiscent of globozoospermia in humans. Disruption of Spaca1 led to the disappearance of the nuclear plate, a dense lining of the nuclear envelope facing the inner acrosomal membrane. This coincided with the failure of acrosomal expansion during spermiogenesis and resulted in the degeneration and disappearance of the acrosome in mature spermatozoa. Thus, these findings clarify part of the cascade leading to globozoospermia. PMID:22949614

  4. Imaging basal ganglia function

    PubMed Central

    BROOKS, DAVID J.

    2000-01-01

    In this review, the value of functional imaging for providing insight into the role of the basal ganglia in motor control is reviewed. Brain activation findings in normal subjects and Parkinson's disease patients are examined and evidence supporting the existence for functionally independent distributed basal ganglia-frontal loops is presented. It is argued that the basal ganglia probably act to focus and filter cortical output, optimising the running of motor programs. PMID:10923986

  5. Cortico-Basal Ganglia Circuit Function in Psychiatric Disease.

    PubMed

    Gunaydin, Lisa A; Kreitzer, Anatol C

    2016-02-10

    Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico-basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders. PMID:26667072

  6. The expanding universe of disorders of the basal ganglia.

    PubMed

    Obeso, Jose A; Rodriguez-Oroz, Maria C; Stamelou, Maria; Bhatia, Kailash P; Burn, David J

    2014-08-01

    The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made. PMID:24954674

  7. [Molecular mechanism of idiopathic basal ganglia calcification].

    PubMed

    Wang, Cheng; Xu, Xuan; Li, Lulu; Wang, Tao; Zhang, Min; Shen, Lu; Tang, Beisha; Liu, Jingyu

    2015-08-01

    Idiopathic basal ganglia calcification (IBGC), also known as Fahr’s disease, is an inheritable neurodegenerative syndrome characterized by mineral deposits in the basal ganglia and other brain regions. Patients with IBGC are often accompanied with movement disorders, cognitive impairment as well as psychiatric abnormalities. So far, no therapeutic drug has been developed for the treatment of IBGC. Recently, genetic studies have identified several genes associated with IBGC, including SLC20A2, PDGFRB, PDGFB, ISG15 and XPR1. Loss-of-function mutations in these genes have been associated with disturbance in phosphate homeostasis in brain regions, the dysfunction of blood-brain barrier as well as enhanced IFN-?/? immunity. In this review, we summarize the latest research progress in the studies on molecular genetics of IBGC, and discuss the molecular mechanisms underlying the pathophysiology of mutations of different genes. PMID:26353387

  8. Automatic Detection of Tuberculosis in Chest Radiographs Using a Combination of Textural, Focal, and Shape Abnormality Analysis.

    PubMed

    Hogeweg, Laurens; Sánchez, Clara I; Maduskar, Pragnya; Philipsen, Rick; Story, Alistair; Dawson, Rodney; Theron, Grant; Dheda, Keertan; Peters-Bax, Liesbeth; van Ginneken, Bram

    2015-12-01

    Tuberculosis (TB) is a common disease with high mortality and morbidity rates worldwide. Automatic systems to detect TB on chest radiographs (CXRs) can improve the efficiency of diagnostic algorithms for pulmonary TB. The diverse manifestation of TB on CXRs from different populations requires a system that can be adapted to deal with different types of abnormalities. A computer aided detection (CAD) system was developed which combines several subscores of supervised subsystems detecting textural, shape, and focal abnormalities into one TB score. A general framework was developed to combine an arbitrary number of subscores: subscores were normalized, collected in a feature vector and then combined using a supervised classifier into one combined score. The method was evaluated on two databases, both consisting of 200 digital CXRs, from: (A) Western high-risk group screening, (B) TB suspect screening in Africa. The subscores and combined score were compared to (1) an external, non-radiological, reference and (2) a radiological reference determined by a human expert. Performance was measured using Receiver Operator Characteristic (ROC) analysis. Different subscores performed best in the two databases. The combined TB score performed better than the individual subscores, except for the external reference in database B. The performances of the independent observer were slightly higher than the combined TB score. Compared to the external reference, differences in performance between the combined TB score and the independent observer were not significant in both databases. Supervised combination to compute an overall TB score allows for a necessary adaptation of the CAD system to different settings or different operational requirements. PMID:25706581

  9. [Information analysis of spinal ganglia].

    PubMed

    Lobko, P I; Kovaleva, D V; Kovalchuk, I E; Pivchenko, P G; Rudenok, V V; Davydova, L A

    2000-01-01

    Information parameters (entropia and redundancy) of cervical and thoracic spinal ganglia of albino rat foetuses, mature animals (cat and dog) and human subjects were analysed. Information characteristics of spinal ganglia were shown to be level-specified and to depend on their functional peculiarities. Information parameters of thoracic spinal ganglia of man and different animals are specie specified and may be used in assessment of morphological structures as information systems. PMID:12629803

  10. Basal ganglia echogenicity in tauopathies.

    PubMed

    Sadowski, Krzysztof; Serafin-Król, Małgorzata; Szlachta, Karol; Friedman, Andrzej

    2015-06-01

    Accumulating data confirm the usefulness of transcranial sonography (TCS) in the diagnosis of Parkinson's disease. The relevance of basal ganglia abnormalities depicted by TCS in atypical parkinsonian syndromes still needs further assessment. In the present study, 20 patients with progressive supranuclear palsy (PSP) and 13 patients with corticobasal syndrome (CBS) were studied with the use of transcranial sonography. Echogenicity of the substantia nigra (SN) and lenticular nucleus (LN) were assessed. 0/20 patients with PSP and 8/12 (66.6 %) patients with CBS were characterized with SN hyperechogenicity. LN hyperechogenicity was observed in 9/20 patients diagnosed with PSP and 0/11 of CBS patients. The combination of SN isoechogenicity and LN hyperechogenicity reached 100 % sensitivity and positive predictive value for the diagnosis of PSP. The results of this study point out that CBS has to be taken into consideration when SN hyperechogenicity is depicted in a patient with parkinsonian syndrome. Normal echogenicity of the SN coexisting with LN hyperechogenicity practically excludes CBS. PMID:25204278

  11. Automatic classification of squamosal abnormality in micro-CT images for the evaluation of rabbit fetal skull defects using active shape models

    NASA Astrophysics Data System (ADS)

    Chen, Antong; Dogdas, Belma; Mehta, Saurin; Bagchi, Ansuman; Wise, L. David; Winkelmann, Christopher

    2014-03-01

    High-throughput micro-CT imaging has been used in our laboratory to evaluate fetal skeletal morphology in developmental toxicology studies. Currently, the volume-rendered skeletal images are visually inspected and observed abnormalities are reported for compounds in development. To improve the efficiency and reduce human error of the evaluation, we implemented a framework to automate the evaluation process. The framework starts by dividing the skull into regions of interest and then measuring various geometrical characteristics. Normal/abnormal classification on the bone segments is performed based on identifying statistical outliers. In pilot experiments using rabbit fetal skulls, the majority of the skeletal abnormalities can be detected successfully in this manner. However, there are shape-based abnormalities that are relatively subtle and thereby difficult to identify using the geometrical features. To address this problem, we introduced a model-based approach and applied this strategy on the squamosal bone. We will provide details on this active shape model (ASM) strategy for the identification of squamosal abnormalities and show that this method improved the sensitivity of detecting squamosal-related abnormalities from 0.48 to 0.92.

  12. Ability of abnormally-shaped human spermatozoa to adhere to and penetrate zona-free hamster eggs: correlation with sperm morphology and postincubation motility.

    PubMed

    Bronson, Richard A; Bronson, Susan K; Oula, Lucila D

    2007-01-01

    A body of evidence indicates that morphologically abnormal human spermatozoa may exhibit impaired ability to fertilize. Yet teratospermia has widely varying etiologies, including associations with varicoceles, following fever, cigarette smoking, and exposure to polychlorinated biphenyls. Abnormalities of sperm shape in mice have also been shown to be associated with autosomal gene mutations. These varying causes of teratospermia could have different molecular consequences reflected in altered sperm function. We studied the ability of morphologically abnormal human sperm to penetrate zona-free hamster eggs as a measure of their ability to undergo an acrosome reaction and gamete membrane fusion. Motile sperm from ejaculates containing 15% normal sperm or less, as judged by World Health Organization (1999) criteria, were recovered by ISolate density centrifugation and capacitated by overnight incubation. Zona-free hamster eggs were inseminated with 1 x 10(6) motile capacitated cells and scored for sperm penetration after 3 hours of coincubation. A significant trend was found between the percent of abnormal spermatozoa within the ejaculate and impaired egg-penetrating ability, reflected in the percent of eggs penetrated, the number of penetrating sperm per egg, and the number of sperm adherent to the oolemma. Because only acrosome-reacted human spermatozoa adhere to the oolemma, these results support the notion that abnormally shaped sperm may exhibit an impaired ability to undergo an acrosome reaction. A correlation was also noted between the loss of motility of sperm following overnight incubation and impairment of their ability to undergo gamete membrane fusion. These results confirm prior findings at the level of the zona pellucida that abnormally shaped sperm exhibit functional abnormalities. However, a wide variation was observed between men in the behavior of such sperm, including occasionally high rates of egg penetration. These observations suggest that assessment of morphology may be an unreliable measure, for the individual, of sperm fertilizing ability and emphasize that sperm function testing is an important part of the evaluation of teratospermia. PMID:17460097

  13. Basal ganglia lesions in children and adults.

    PubMed

    Bekiesinska-Figatowska, Monika; Mierzewska, Hanna; Jurkiewicz, El?bieta

    2013-05-01

    The term "basal ganglia" refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) - to a lesser degree - allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or - more frequently - bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic-ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive. PMID:23313708

  14. [Anti-basal ganglia antibody].

    PubMed

    Hayashi, Masaharu

    2013-04-01

    Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS. PMID:23568985

  15. Magnetic resonance imaging findings in bilateral basal ganglia lesions.

    TOXLINE Toxicology Bibliographic Information

    Lim CC

    2009-09-01

    INTRODUCTION: Radiologists may encounter bilaterally symmetrical abnormalities of the basal ganglia on magnetic resonance imaging (MRI), typically in the context of diffuse systemic, toxic or metabolic diseases. A systematic approach and broad knowledge of pathology causing this uncommon group of conditions would be useful.MATERIALS AND METHODS: This review uses illustrative images to highlight metabolic conditions, such as Leigh's syndrome, citrullinaemia, hypoglycaemia or carbon monoxide poisoning, as well as other causes of bilateral basal ganglia lesions such as osmotic myelinolysis, deep cerebral venous thrombosis and Creutzfeldt-Jakob disease.RESULTS: Careful assessment of radiological findings outside the basal ganglia, such as involvement of the cortex, white matter, thalamus and pons, together with clinical correlation, may be helpful in narrowing the differential diagnosis, and directing further radiological, biochemical or genetic investigations. Recent advances in MR technology have resulted in newer techniques including diffusion-weighted (DW) MR imaging and MR spectroscopy (MRS); these may be helpful if appropriately used.CONCLUSIONS: Abnormal MRI findings in the basal ganglia should not be interpreted in isolation. A systematic approach including DW MR imaging, MRS, and a broad knowledge of diffuse systemic, toxic or metabolic diseases is helpful.

  16. Anatomical MRI study of basal ganglia in major depressive disorder.

    PubMed

    Lacerda, Acioly L T; Nicoletti, Mark A; Brambilla, Paolo; Sassi, Roberto B; Mallinger, Alan G; Frank, Ellen; Kupfer, David J; Keshavan, Matcheri S; Soares, Jair C

    2003-11-30

    The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age+/-S.D.=41+/-11 years) and 48 healthy controls (29 M; age+/-S.D.=35+/-10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder. PMID:14623065

  17. Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

    PubMed Central

    Criswell, Susan R; Perlmutter, Joel S; Huang, John L; Golchin, Nima; Flores, Hubert P; Hobson, Angela; Aschner, Michael; Erikson, Keith M; Checkoway, Harvey; Racette, Brad A

    2013-01-01

    Objectives Manganese exposure leads to diffuse cerebral metal deposition with the highest concentration in the globus pallidus associated with increased T1-weighted MRI signal. T1 signal intensity in extra-pallidal basal ganglia (caudate and putamen) has not been studied in occupationally exposed workers. Diffusion weighted imaging is a non-invasive measure of neuronal damage and may provide a quantification of neurotoxicity associated with welding and manganese exposure. This study investigated extra-pallidal T1 basal ganglia signal intensity as a marker of manganese exposure and basal ganglia diffusion weighted imaging abnormalities as a potential marker of neurotoxicity. Methods A 3T MR case:control imaging study was performed on 18 welders and 18 age- and gender-matched controls. Basal ganglia regions of interest were identified for each subject. T1-weighted intensity indices and apparent diffusion coefficients were generated for each region. Results All regional indices were higher in welders than controls (p≤0.05). Combined basal ganglia (ρ=0.610), caudate (ρ=0.645), anterior (ρ=0.595) and posterior putamen (ρ=0.511) indices were more correlated with exposure than pallidal (ρ=0.484) index. Welder apparent diffusion coefficient values were lower than controls for globus pallidus (p=0.03) and anterior putamen (p=0.004). Conclusions Welders demonstrated elevated T1 indices throughout the basal ganglia. Combined basal ganglia, caudate and putamen indices were more correlated with exposure than pallidal index suggesting more inclusive basal ganglia sampling results in better exposure markers. Elevated indices were associated with diffusion weighted abnormalities in the pallidum and anterior putamen suggesting neurotoxicity in these regions. PMID:22447645

  18. The cerebellum communicates with the basal ganglia.

    PubMed

    Hoshi, Eiji; Tremblay, Léon; Féger, Jean; Carras, Peter L; Strick, Peter L

    2005-11-01

    The cerebral cortex is interconnected with two major subcortical structures: the basal ganglia and the cerebellum. How and where cerebellar circuits interact with basal ganglia circuits has been a longstanding question. Using transneuronal transport of rabies virus in macaques, we found that a disynaptic pathway links an output stage of cerebellar processing, the dentate nucleus, with an input stage of basal ganglia processing, the striatum. PMID:16205719

  19. Basal ganglia correlates of fatigue in young adults.

    PubMed

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Kotozaki, Yuka; Shinada, Takamitsu; Maruyama, Tsukasa; Sekiguchi, Atsushi; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Magistro, Daniele; Sakaki, Kohei; Jeong, Hyeonjeong; Sasaki, Yukako; Kawashima, Ryuta

    2016-01-01

    Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward. PMID:26893077

  20. Basal ganglia correlates of fatigue in young adults

    PubMed Central

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Kotozaki, Yuka; Shinada, Takamitsu; Maruyama, Tsukasa; Sekiguchi, Atsushi; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Magistro, Daniele; Sakaki, Kohei; Jeong, Hyeonjeong; Sasaki, Yukako; Kawashima, Ryuta

    2016-01-01

    Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward. PMID:26893077

  1. Basal ganglia activity patterns in parkinsonism and computational modeling of their downstream effects

    PubMed Central

    Rubin, Jonathan E.; McIntyre, Cameron C.; Turner, Robert S.; Wichmann, Thomas

    2012-01-01

    The availability of suitable animal models and of the opportunity to record electrophysiologic data in movement disorder patients undergoing neurosurgical procedures has allowed researchers to investigate parkinsonism-related changes in neuronal firing patterns in the basal ganglia and associated areas of thalamus and cortex. These studies have shown that parkinsonism is associated with increased activity in the basal ganglia output nuclei, along with an increase in burst discharges, oscillatory firing, and synchronous firing patterns throughout the basal ganglia. Computational approaches have the potential to play an important role in the interpretation of these data. Such efforts can provide a formalized view of neuronal interactions in the network of connections between basal ganglia, thalamus and cortex, allow for the exploration of possible contributions of particular network components to parkinsonism, and potentially result in new conceptual frameworks and hypotheses that can be subjected to biological testing. It has proven very difficult, however, to integrate the wealth of the experimental findings into coherent models of the disease. In this review, we provide an overview of the abnormalities in neuronal activity that have been associated with parkinsonism. Subsequently, we discuss some particular efforts to model the pathophysiologic mechanisms that may link abnormal basal ganglia activity to the cardinal parkinsonian motor signs and may help explain the mechanisms underlying the therapeutic efficacy of deep brain stimulation for Parkinson’s disease. We emphasize the logical structure of these computational studies, making clear the assumptions from which they proceed and the consequences and predictions that follow from these assumptions. PMID:22805066

  2. Developmental Venous Anomaly With Asymmetrical Basal Ganglia Calcification: Two Case Reports and Review of the Literature

    PubMed Central

    Sarp, Ali Firat; Batki, Ozan; Gelal, Mustafa Fazil

    2015-01-01

    Developmental venous anomaly (DVA) is a common lesion formerly known as venous angioma. DVAs drain normal brain parenchyma; however, parenchymal abnormalities surrounding DVAs have been reported. Unilateral putamen and caudate calcification in the drainage territory of DVAs has so far been reported in 7 cases, all with deep venous drainage. We present two additional cases of DVAs, one with superficial and the other one with deep venous drainage, associated with basal ganglia calcifications. We emphasize that DVAs should be in the differential diagnosis of unilateral basal ganglia calcifications. PMID:26557273

  3. The Basal Ganglia-Circa 1982

    NASA Technical Reports Server (NTRS)

    Mehler, William R.

    1981-01-01

    Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

  4. The Cerebellum and Basal Ganglia are Interconnected

    PubMed Central

    Strick, Peter L.

    2012-01-01

    The cerebellum and the basal ganglia are major subcortical nuclei that control multiple aspects of behavior largely through their interactions with the cerebral cortex. Discrete multisynaptic loops connect both the cerebellum and the basal ganglia with multiple areas of the cerebral cortex. Interactions between these loops have traditionally been thought to occur mainly at the level of the cerebral cortex. Here, we review a series of recent anatomical studies in nonhuman primates that challenge this perspective. We show that the anatomical substrate exists for substantial interactions between the cerebellum and the basal ganglia. Furthermore, we discuss how these pathways may provide a useful framework for understanding cerebellar contributions to the manifestation of two prototypical basal ganglia disorders, Parkinson’s disease and dystonia. PMID:20811947

  5. Synaptic organisation of the basal ganglia

    PubMed Central

    BOLAM, J. P.; HANLEY, J. J.; BOOTH, P. A. C.; BEVAN, M. D.

    2000-01-01

    The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context-dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is ‘processed’ within the striatum and passed via the so-called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical ‘premotor’ regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed-forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic integration of functionally diverse information derived from the cortex. It is concluded that the essential concept of the direct and indirect pathways of information flow through the basal ganglia remains intact but that the role of the indirect pathway is more complex than previously suggested and that neurons of the globus pallidus are in a position to control the activity of virtually the whole of the basal ganglia. PMID:10923985

  6. Basal Ganglia Damage in Experimental Subarachnoid Hemorrhage.

    PubMed

    Zhang, Haining; Okubo, Shuichi; Hua, Ya; Keep, Richard F; Xi, Guohua

    2016-01-01

    Research suggests that early brain injury following subarachnoid hemorrhage (SAH) is a primary therapeutic target, and early SAH-induced basal ganglia injury is not well studied. The present study examined basal ganglia injury in a rat model of SAH. Adult male Sprague-Dawley rats (n?=?78) weighing 275-300 g underwent endovascular perforation to mimic aneurysmal SAH. Sham rats (n?=?12) underwent the same procedure but without perforation. Magnetic resonance imaging (T2 MRI) was performed at 24 h after SAH to measure ventricle volumes and brain T2 lesion. Hydrocephalus in SAH rats was defined as a ventricular volume greater than three standard deviations above that in shams. Western blotting and immunochemistry were utilized to assess basal ganglia damage. Sixty rats survived the SAH and 40 % of those animals had T2 lesions in the basal ganglia. Twenty-six SAH rats had hydrocephalus. Rats with hydrocephalus had higher incidence of basal ganglia lesion (69 vs. 18 % in rats without hydrocephalus; p?ganglia neuronal injury was also determined by examining the levels of dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32). We found that rats with hydrocephalus had more severe basal ganglia injury with greater DARPP-32 depletion (DARPP-32/beta-actin: 0.38?±?0.32 vs. 0.86?±?0.45 in rats without hydrocephalus and 1.10?±?0.28 in sham, p?ganglia damage, which is associated with hydrocephalus development. PMID:26463938

  7. Extrastriatal Dopaminergic Circuits of the Basal Ganglia

    PubMed Central

    Rommelfanger, Karen S.; Wichmann, Thomas

    2010-01-01

    The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction. PMID:21103009

  8. Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures

    PubMed Central

    Kotsenas, Amy L.; Britton, Jeffrey W.; McKeon, Andrew; Watson, Robert E.; Klein, Christopher J.; Boeve, Bradley F.; Lowe, Val; Ahlskog, J. Eric; Shin, Cheolsu; Boes, Christopher J.; Crum, Brian A.; Laughlin, Ruple S.; Pittock, Sean J.

    2015-01-01

    Objective: To characterize the clinical features and MRI abnormalities of leucine-rich glioma-inactivated 1 (LGI1)-autoantibody (Ab) faciobrachial dystonic seizures (FBDS). Methods: Forty-eight patients with LGI1-Ab encephalopathy were retrospectively identified by searching our clinical and serologic database from January 1, 2002, to June 1, 2015. Of these, 26 met inclusion criteria for this case series: LGI1-Ab seropositivity and FBDS. In a separate analysis of all 48 patients initially identified, the MRIs of patients with (n = 26) and without (n = 22) FBDS were compared by 2 neuroradiologists blinded to the clinical details. Results: The median age of the 26 included patients was 62.5 years (range 37–78); 65% were men. FBDS involved arm (26), face (22), and leg (12). Ten were previously diagnosed as psychogenic. Ictal EEGs were normal in 20 of 23 assessed. Basal ganglia T1 and T2 signal abnormalities were detected in 11 patients (42%), with excellent agreement between neuroradiologists (κ scores of 0.86 and 0.93, respectively), and included T1 hyperintensity alone (2), T2 hyperintensity alone (1), or both (8). The T1 hyperintensities persisted longer than the T2 hyperintensities (median 11 weeks vs 1 week, p = 0.02). Improvement with immunotherapy (18/18) was more frequent than with antiepileptic medications (10/24). A separate analysis of all 48 patients initially identified with LGI1-Ab encephalopathy showed that basal ganglia MRI abnormalities were present in 11 of 26 with FBDS but not present in those without FBDS (0/22) (p < 0.001). In contrast, mesial temporal MRI abnormalities were less common among those with FBDS (42%) than those without (91%) (p < 0.001). Conclusions: Basal ganglia T1 hyperintensity is a clinically useful MRI biomarker of LGI1-Ab FBDS and suggests a basal ganglia localization. PMID:26468474

  9. Psychosis revealing familial idiopathic basal ganglia calcification.

    PubMed

    Nicolas, Gaël; Guillin, Olivier; Borden, Alaina; Bioux, Sandrine; Lefaucheur, Romain; Hannequin, Didier

    2013-01-01

    We describe the case of a 39-year-old woman presenting with auditory hallucinations and delusions responsive to antipsychotic drugs. Computerized tomography scans revealed basal ganglia calcifications in the proband and in her two asymptomatic parents. Extensive etiological clinicobiological assessment allowed us to exclude known causes of brain calcifications and diagnose familial idiopathic basal ganglia calcification (IBGC). Neurological symptoms associated with psychiatric symptoms are common in IBGC. Nevertheless, purely psychiatric presentations, as demonstrated by the present case, are possible. However, a fortuitous association between asymptomatic IBGC and schizophrenia cannot be ruled out. Only brain imaging, followed by an extensive etiological assessment, allows for diagnosis of this rare disorder. PMID:23122487

  10. The connectome of the basal ganglia.

    PubMed

    Schmitt, Oliver; Eipert, Peter; Kettlitz, Richard; Leßmann, Felix; Wree, Andreas

    2016-03-01

    The basal ganglia of the laboratory rat consist of a few core regions that are specifically interconnected by efferents and afferents of the central nervous system. In nearly 800 reports of tract-tracing investigations the connectivity of the basal ganglia is documented. The readout of connectivity data and the collation of all the connections of these reports in a database allows to generate a connectome. The collation, curation and analysis of such a huge amount of connectivity data is a great challenge and has not been performed before (Bohland et al. PloS One 4:e7200, 2009) in large connectomics projects based on meta-analysis of tract-tracing studies. Here, the basal ganglia connectome of the rat has been generated and analyzed using the consistent cross-platform and generic framework neuroVIISAS. Several advances of this connectome meta-study have been made: the collation of laterality data, the network-analysis of connectivity strengths and the assignment of regions to a hierarchically organized terminology. The basal ganglia connectome offers differences in contralateral connectivity of motoric regions in contrast to other regions. A modularity analysis of the weighted and directed connectome produced a specific grouping of regions. This result indicates a correlation of structural and functional subsystems. As a new finding, significant reciprocal connections of specific network motifs in this connectome were detected. All three principal basal ganglia pathways (direct, indirect, hyperdirect) could be determined in the connectome. By identifying these pathways it was found that there exist many further equivalent pathways possessing the same length and mean connectivity weight as the principal pathways. Based on the connectome data it is unknown why an excitation pattern may prefer principal rather than other equivalent pathways. In addition to these new findings the local graph-theoretical features of regions of the connectome have been determined. By performing graph theoretical analyses it turns out that beside the caudate putamen further regions like the mesencephalic reticular formation, amygdaloid complex and ventral tegmental area are important nodes in the basal ganglia connectome. The connectome data of this meta-study of tract-tracing reports of the basal ganglia are available for further network studies, the integration into neocortical connectomes and further extensive investigations of the basal ganglia dynamics in population simulations. PMID:25432770

  11. Psychopharmacologic intervention after hemorrhagic basal ganglia damage.

    PubMed

    Al Owesie, Rafat Mohammed; Morton, Catherine Saino

    2012-11-15

    Traumatic brain injury (TBI) can result in cognitive and behavioral impairments such as poor attention, learning, memory and planning ability and uncontrolled crying that can be more persistent problems than the physical disabilities. Cognitive enhancers have been shown to improve cognitive and behavioral impairments in patients with hemorrhagic basal ganglia lesions as well as other forms of TBI. There is little research about the use of cognitive enhancers after hemorrhagic basal ganglia damage. We present a case of a 38 year old male who made significant recovery with the use of cognitive enhancers. PMID:22795553

  12. Altered Basal Ganglia Network Integration in Schizophrenia

    PubMed Central

    Duan, Mingjun; Chen, Xi; He, Hui; Jiang, Yuchao; Jiang, Sisi; Xie, Qiankun; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-01-01

    The basal ganglia involve in a range of functions that are disturbed in schizophrenia patients. This study decomposed the resting-state data of 28 schizophrenia patients and 31 healthy controls with spatial independent component analysis and identified increased functional integration in the bilateral caudate nucleus in schizophrenia patients. Further, the caudate nucleus in patients showed altered functional connection with the prefrontal area and cerebellum. These results identified the importance of basal ganglia in schizophrenia patients. Clinical Trial Registration: Chinese Clinical Trial Registry. Registration number ChiCTR-RCS-14004878. PMID:26528167

  13. Coupling in the cortico-basal ganglia circuit is aberrant in the ketamine model of schizophrenia.

    PubMed

    Cordon, Ivan; Nicolás, María Jesús; Arrieta, Sandra; Lopetegui, Eneko; López-Azcárate, Jon; Alegre, Manuel; Artieda, Julio; Valencia, Miguel

    2015-08-01

    Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals? behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients. PMID:25910422

  14. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  15. The basal ganglia’s contributions to perceptual decision-making

    PubMed Central

    Ding, Long; Gold, Joshua I.

    2013-01-01

    Perceptual decision-making is a computationally demanding process that requires the brain to interpret incoming sensory information in the context of goals, expectations, preferences, and other factors. These integrative processes engage much of cortex but also require contributions from subcortical structures to affect behavior. Here we summarize recent evidence supporting specific computational roles of the basal ganglia in perceptual decision-making. These roles likely share common mechanisms with the basal ganglia’s other, more well-established functions in motor control, learning, and other aspects of cognition and thus can provide insights into the general roles of this important subcortical network in higher brain function. PMID:23972593

  16. Genetics Home Reference: Biotin-thiamine-responsive basal ganglia disease

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Biotin-thiamine-responsive basal ganglia disease On this page: ... names Glossary definitions Reviewed January 2014 What is biotin-thiamine-responsive basal ganglia disease? Biotin-thiamine-responsive ...

  17. Dopaminergic Control of the Exploration-Exploitation Trade-Off via the Basal Ganglia

    PubMed Central

    Humphries, Mark D.; Khamassi, Mehdi; Gurney, Kevin

    2012-01-01

    We continuously face the dilemma of choosing between actions that gather new information or actions that exploit existing knowledge. This “exploration-exploitation” trade-off depends on the environment: stability favors exploiting knowledge to maximize gains; volatility favors exploring new options and discovering new outcomes. Here we set out to reconcile recent evidence for dopamine’s involvement in the exploration-exploitation trade-off with the existing evidence for basal ganglia control of action selection, by testing the hypothesis that tonic dopamine in the striatum, the basal ganglia’s input nucleus, sets the current exploration-exploitation trade-off. We first advance the idea of interpreting the basal ganglia output as a probability distribution function for action selection. Using computational models of the full basal ganglia circuit, we showed that, under this interpretation, the actions of dopamine within the striatum change the basal ganglia’s output to favor the level of exploration or exploitation encoded in the probability distribution. We also found that our models predict striatal dopamine controls the exploration-exploitation trade-off if we instead read-out the probability distribution from the target nuclei of the basal ganglia, where their inhibitory input shapes the cortical input to these nuclei. Finally, by integrating the basal ganglia within a reinforcement learning model, we showed how dopamine’s effect on the exploration-exploitation trade-off could be measurable in a forced two-choice task. These simulations also showed how tonic dopamine can appear to affect learning while only directly altering the trade-off. Thus, our models support the hypothesis that changes in tonic dopamine within the striatum can alter the exploration-exploitation trade-off by modulating the output of the basal ganglia. PMID:22347155

  18. Abnormal selective area growth of irregularly-shaped GaN structures on the apex of GaN pyramids and its application for wide spectral emission

    NASA Astrophysics Data System (ADS)

    Yu, Yeon Su; Lee, Jun Hyeong; Ahn, Hyung Soo; Yang, Min

    2014-12-01

    We report on the growth and the characterization of three-dimensional randomly-shaped InGaN/GaN structures selectively grown on the apex of GaN pyramids for the purpose of enlarging the emission spectral range. We found that the variations in the shape and the size of the three-dimensional GaN structures depend on the growth temperature and the surface area for selective growth under intentional turbulence in the gas stream. The selectively grown GaN structures grown at 1020 °C have irregular shape, while the samples grown at 1100 °C have rather uniform hexagonal pyramidal shapes. Irregularly shaped GaN structures were also obtained on the apex of GaN pyramids when the SiO2 mask was removed to 1/10 of the total height of the underlying GaN pyramid. When only 1/5 of the SiO2 mask was removed, however, the selectively grown GaN structures had similar hexagonal pyramidal shapes resembling those of the underlying GaN pyramids. The CL (Cathodoluminescence) spectra of the InGaN layers grown on the randomly shaped GaN structures showed a wide emission spectral range from 388 to 433 nm due to the non-uniform thickness and spatially inhomogeneous indium composition of the InGaN layers. This new selective growth method might have great potential for applications of non-phosphor white light emitting diodes (LEDs) with optimized growth conditions for InGaN active layers of high indium composition and with optimum process for fabrication of electrodes for electrical injection.

  19. Herpes Simplex Virus 1 Reactivates from Autonomic Ciliary Ganglia Independently from Sensory Trigeminal Ganglia To Cause Recurrent Ocular Disease

    PubMed Central

    Lee, Sungseok; Ives, Angela M.

    2015-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. HSV-1 reactivates from latency to cause recurrent orofacial disease, and while HSV-1 also causes genital lesions, HSV-2 recurs more efficiently in the genital region and rarely causes ocular disease. The mechanisms regulating these anatomical preferences are unclear. To determine whether differences in latent infection and reactivation in autonomic ganglia contribute to differences in HSV-1 and HSV-2 anatomical preferences for recurrent disease, we compared HSV-1 and HSV-2 clinical disease, acute and latent viral loads, and viral gene expression in sensory trigeminal and autonomic superior cervical and ciliary ganglia in a guinea pig ocular infection model. HSV-2 produced more severe acute disease, correlating with higher viral DNA loads in sensory and autonomic ganglia, as well as higher levels of thymidine kinase expression, a marker of productive infection, in autonomic ganglia. HSV-1 reactivated in ciliary ganglia, independently from trigeminal ganglia, to cause more frequent recurrent symptoms, while HSV-2 replicated simultaneously in autonomic and sensory ganglia to cause more persistent disease. While both HSV-1 and HSV-2 expressed the latency-associated transcript (LAT) in the trigeminal and superior cervical ganglia, only HSV-1 expressed LAT in ciliary ganglia, suggesting that HSV-2 is not reactivation competent or does not fully establish latency in ciliary ganglia. Thus, differences in replication and viral gene expression in autonomic ganglia may contribute to differences in HSV-1 and HSV-2 acute and recurrent clinical disease. IMPORTANCE Herpes simplex virus 1 (HSV-1) and HSV-2 establish latent infections, from which the viruses reactivate to cause recurrent disease throughout the life of the host. However, the viruses exhibit different manifestations and frequencies of recurrent disease. HSV-1 and HSV-2 establish latency in both sensory and autonomic ganglia. Autonomic ganglia are more responsive than sensory ganglia to stimuli associated with recurrent disease in humans, such as stress and hormone fluctuations, suggesting that autonomic ganglia may play an important role in recurrent disease. We show that HSV-1 can reactivate from autonomic ganglia, independently from sensory ganglia, to cause recurrent ocular disease. We found no evidence that HSV-2 could reactivate from autonomic ganglia independently from sensory ganglia after ocular infection, but HSV-2 did replicate in both ganglia simultaneously to cause persistent disease. Thus, viral replication and reactivation in autonomic ganglia contribute to different clinical disease manifestations of HSV-1 and HSV-2 after ocular infection. PMID:26041294

  20. Modulation of the basal ganglia dopaminergic system in a transgenic mouse exhibiting dystonia-like features

    PubMed Central

    Giannakopoulou, D.; Armata, I. A.; Mitsacos, A.; Shashidharan, P.; Giompres, P.

    2011-01-01

    Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected) transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates A decrease in the density of striatal D2 binding sites, measured by [3H]raclopride binding, and D2 mRNA expression in substantia nigra pars compacta (SNpc) was revealed in affected an unaffected transgenic mice when compared with non-transgenic. No difference in D1 receptor binding and DAT binding, measured by [3H]SCH23390 and [3H]WIN35428 binding, respectively, was found in striatum of transgenic animals. In SNpc, increased levels of DAT binding sites were observed in affected and unaffected animals compared to non-transgenic, whereas no change in DAT mRNA expression was found. Our results show selective neurochemical changes in the basal ganglia dopaminergic system, suggesting a possible involvement in the pathophysiology of dystonialike motor hyperactivity. PMID:21136125

  1. Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia

    ERIC Educational Resources Information Center

    Brown, S.M.; Kieffaber, P.D.; Carroll, C.A.; Vohs, J.L.; Tracy, J.A.; Shekhar, A.; O'Donnell, B.F.; Steinmetz, J.E.; Hetrick, W.P.

    2005-01-01

    Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar…

  2. Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia

    ERIC Educational Resources Information Center

    Brown, S.M.; Kieffaber, P.D.; Carroll, C.A.; Vohs, J.L.; Tracy, J.A.; Shekhar, A.; O'Donnell, B.F.; Steinmetz, J.E.; Hetrick, W.P.

    2005-01-01

    Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar…

  3. Control of Basal Ganglia Output by Direct and Indirect Pathway Projection Neurons

    PubMed Central

    Freeze, Benjamin S.; Kravitz, Alexxai V.; Hammack, Nora; Berke, Joshua D.

    2013-01-01

    The direct and indirect efferent pathways from striatum ultimately reconverge to influence basal ganglia output nuclei, which in turn regulate behavior via thalamocortical and brainstem motor circuits. However, the distinct contributions of these two efferent pathways in shaping basal ganglia output are not well understood. We investigated these processes using selective optogenetic control of the direct and indirect pathways, in combination with single-unit recording in the basal ganglia output nucleus substantia nigra pars reticulata (SNr) in mice. Optogenetic activation of striatal direct and indirect pathway projection neurons produced diverse cellular responses in SNr neurons, with stimulation of each pathway eliciting both excitations and inhibitions. Despite this response heterogeneity, the effectiveness of direct pathway stimulation in producing movement initiation correlated selectively with the subpopulation of inhibited SNr neurons. In contrast, effective indirect pathway-mediated motor suppression was most strongly influenced by excited SNr neurons. Our results support the theory that key basal ganglia output neurons serve as an inhibitory gate over motor output that can be opened or closed by striatal direct and indirect pathways, respectively. PMID:24259575

  4. Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia

    PubMed Central

    Wang, Xu-yang; Gu, Pei-yuan; Chen, Shi-wen; Gao, Wen-wei; Tian, Heng-li; Lu, Xiang-he; Zheng, Wei-ming; Zhuge, Qi-chuan; Hu, Wei-xing

    2015-01-01

    In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1–5 and L7–S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy. PMID:26807126

  5. Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease).

    PubMed

    Oliveira, J R M; Spiteri, E; Sobrido, M J; Hopfer, S; Klepper, J; Voit, T; Gilbert, J; Wszolek, Z K; Calne, D B; Stoessl, A J; Hutton, M; Manyam, B V; Boller, F; Baquero, M; Geschwind, D H

    2004-12-14

    Familial idiopathic basal ganglia calcification (IBGC, Fahr disease) is an inherited neurologic condition characterized by basal ganglia and extra-basal ganglia brain calcifications, parkinsonism, and neuropsychiatric symptoms. The authors examined six families for linkage to the previously identified genetic locus (IBGC1) located on chromosome 14q. The authors found evidence against linkage to IBGC1 in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC. PMID:15596772

  6. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    PubMed

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy. PMID:7699389

  7. The Basal Ganglia and Adaptive Motor Control

    NASA Astrophysics Data System (ADS)

    Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

    1994-09-01

    The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

  8. Mössbauer spectroscopy of Basal Ganglia

    SciTech Connect

    Miglierini, Marcel; Lančok, Adriana; Kopáni, Martin; Boča, Roman

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  9. Cannabinoids and neuroprotection in basal ganglia disorders.

    PubMed

    Sagredo, Onintza; García-Arencibia, Moisés; de Lago, Eva; Finetti, Simone; Decio, Alessandra; Fernández-Ruiz, Javier

    2007-08-01

    Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity, calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders including Parkinson's disease and Huntington's chorea, two chronic diseases that are originated as a consequence of the degeneration of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases have been still scarcely explored at the clinical level for a possible application of cannabinoids to delay the progressive degeneration of the basal ganglia. However, the preclinical evidence seems to be solid and promising. There are two key mechanisms involved in the neuroprotection by cannabinoids in experimental models of these two disorders: first, a cannabinoid receptor-independent mechanism aimed at producing a decrease in the oxidative injury and second, an induction/upregulation of cannabinoid CB2 receptors, mainly in reactive microglia, that is capable to regulate the influence of these glial cells on neuronal homeostasis. Considering the relevance of these preclinical data and the lack of efficient neuroprotective strategies in both disorders, we urge the development of further studies that allow that the promising expectatives generated for these molecules progress from the present preclinical evidence till a real clinical application. PMID:17952653

  10. Gait function in high-functioning autism and Asperger's disorder : evidence for basal-ganglia and cerebellar involvement?

    PubMed

    Rinehart, Nicole J; Tonge, Bruce J; Bradshaw, John L; Iansek, Robert; Enticott, Peter G; McGinley, Jenny

    2006-08-01

    Gait abnormalities have been widely reported in individuals with autism and Asperger's disorder. There is controversy as to whether the cerebellum or the basal-ganglia frontostriatal regions underpin these abnormalities. This is the first direct comparison of gait and upper-body postural features in autism and Asperger's disorder. Clinical and control groups were matched according to age, height, weight, performance, and full scale IQ. Consistent with Hallet's (1993) cerebellar-gait hypothesis, the autistic group showed significantly increased stride-length variability in their gait in comparison to control and Asperger's disorder participants. No quantitative gait deficits were found for the Asperger's disorder group. In support of Damasio and Maurer's (1982) basal-ganglia frontostriatal-gait hypothesis, both clinical groups were rated as showing abnormal arm posturing, however, only the Asperger's group were rated as significantly different from controls in terms of head and trunk posturing. While DSM-IV-TR suggests that Asperger's disorder, but not autism, is associated with motoric clumsiness, our data suggest that both clinical groups are uncoordinated and lacking in motor smoothness. Gait differences in autism and Asperger's disorder were suggested to reflect differential involvement of the cerebellum, with commonalities reflecting similar involvement of the basal-ganglia frontostriatal region. PMID:16554961

  11. The basal ganglia and cerebellum interact in the expression of dystonic movement

    PubMed Central

    Neychev, Vladimir K.; Fan, Xueliang; Mitev, V. I.; Hess, Ellen J.

    2008-01-01

    Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements or abnormal posturing. Traditional views place responsibility for dystonia with dysfunction of basal ganglia circuits, yet recent evidence has pointed towards cerebellar circuits as well. In the current studies we used two strategies to explore the hypothesis that the expression of dystonic movements depends on influences from a motor network that includes both the basal ganglia and cerebellum. The first strategy was to evaluate the consequences of subthreshold lesions of the striatum in two different animal models where dystonic movements are thought to originate from abnormal cerebellar function. The second strategy employed microdialysis to search for changes in striatal dopamine release in these two animal models where the cerebellum has been already implicated. One of the animal models involved tottering mice, which exhibit paroxysmal dystonia due to an inherited defect affecting calcium channels. In keeping with prior results implicating the cerebellum in this model, surgical removal of the cerebellum eliminated their dystonic attacks. In contrast, subclinical lesions of the striatum with either 6-hydroxydopamine (6OHDA) or quinolinic acid (QA) exaggerated their dystonic attacks. Microdialysis of the striatum revealed dystonic attacks in tottering mice to be associated with a significant reduction in extracellular striatal dopamine. The other animal model involved the induction of dystonia via pharmacological excitation of the cerebellar cortex by local application of kainic acid in normal mice. In this model the site of stimulation determines the origin of dystonia in the cerebellum. However, subclinical striatal lesions with either 6OHDA or QA again exaggerated their generalized dystonia. When dystonic movements were triggered by pharmacological stimulation of the cerebellum, microdialysis revealed significant reductions in striatal dopamine release. These results demonstrate important functional relationships between cerebellar and basal ganglia circuits in two different animal models of dystonia. They suggest that expression of dystonic movements depends on influences from both basal ganglia and cerebellum in both models. These results support the hypothesis that dystonia may result from disruption of a motor network involving both the basal ganglia and cerebellum, rather than isolated dysfunction of only one motor system. PMID:18669484

  12. Mineralizing angiopathy with basal ganglia stroke in an infant

    PubMed Central

    Jain, Puneet; Kishore, Praveen; Bhasin, Jasjit Singh; Arya, Subhash Chand

    2015-01-01

    Basal ganglia stroke is known following trivial head trauma. Recently a distinct clinic-radiological entity termed ‘mineralizing angiopathy’ was described. We report an infant who developed basal ganglia stroke following trivial fall. His clinic-radiological features are described. PMID:26019426

  13. Herpes Simplex Virus 1 Reactivates from Autonomic Ciliary Ganglia Independently from Sensory Trigeminal Ganglia To Cause Recurrent Ocular Disease.

    PubMed

    Lee, Sungseok; Ives, Angela M; Bertke, Andrea S

    2015-08-01

    Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. HSV-1 reactivates from latency to cause recurrent orofacial disease, and while HSV-1 also causes genital lesions, HSV-2 recurs more efficiently in the genital region and rarely causes ocular disease. The mechanisms regulating these anatomical preferences are unclear. To determine whether differences in latent infection and reactivation in autonomic ganglia contribute to differences in HSV-1 and HSV-2 anatomical preferences for recurrent disease, we compared HSV-1 and HSV-2 clinical disease, acute and latent viral loads, and viral gene expression in sensory trigeminal and autonomic superior cervical and ciliary ganglia in a guinea pig ocular infection model. HSV-2 produced more severe acute disease, correlating with higher viral DNA loads in sensory and autonomic ganglia, as well as higher levels of thymidine kinase expression, a marker of productive infection, in autonomic ganglia. HSV-1 reactivated in ciliary ganglia, independently from trigeminal ganglia, to cause more frequent recurrent symptoms, while HSV-2 replicated simultaneously in autonomic and sensory ganglia to cause more persistent disease. While both HSV-1 and HSV-2 expressed the latency-associated transcript (LAT) in the trigeminal and superior cervical ganglia, only HSV-1 expressed LAT in ciliary ganglia, suggesting that HSV-2 is not reactivation competent or does not fully establish latency in ciliary ganglia. Thus, differences in replication and viral gene expression in autonomic ganglia may contribute to differences in HSV-1 and HSV-2 acute and recurrent clinical disease. PMID:26041294

  14. Protocadherin 17 regulates presynaptic assembly in topographic corticobasal Ganglia circuits.

    PubMed

    Hoshina, Naosuke; Tanimura, Asami; Yamasaki, Miwako; Inoue, Takeshi; Fukabori, Ryoji; Kuroda, Teiko; Yokoyama, Kazumasa; Tezuka, Tohru; Sagara, Hiroshi; Hirano, Shinji; Kiyonari, Hiroshi; Takada, Masahiko; Kobayashi, Kazuto; Watanabe, Masahiko; Kano, Masanobu; Nakazawa, Takanobu; Yamamoto, Tadashi

    2013-06-01

    Highly topographic organization of neural circuits exists for the regulation of various brain functions in corticobasal ganglia circuits. Although neural circuit-specific refinement during synapse development is essential for the execution of particular neural functions, the molecular and cellular mechanisms for synapse refinement are largely unknown. Here, we show that protocadherin 17 (PCDH17), one of the nonclustered δ2-protocadherin family members, is enriched along corticobasal ganglia synapses in a zone-specific manner during synaptogenesis and regulates presynaptic assembly in these synapses. PCDH17 deficiency in mice causes facilitated presynaptic vesicle accumulation and enhanced synaptic transmission efficacy in corticobasal ganglia circuits. Furthermore, PCDH17(-/-) mice exhibit antidepressant-like phenotypes that are known to be regulated by corticobasal ganglia circuits. Our findings demonstrate a critical role for PCDH17 in the synaptic development of specific corticobasal ganglia circuits and suggest the involvement of PCDH17 in such circuits in depressive behaviors. PMID:23684785

  15. Basal Ganglia Mechanisms Underlying Precision Grip Force Control

    PubMed Central

    Prodoehl, Janey; Corcos, Daniel M.; Vaillancourt, David E.

    2009-01-01

    The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force. PMID:19428499

  16. Calcium Signaling in Intact Dorsal Root Ganglia

    PubMed Central

    Gemes, Geza; Rigaud, Marcel; Koopmeiners, Andrew S.; Poroli, Mark J.; Zoga, Vasiliki; Hogan, Quinn H.

    2013-01-01

    Background Ca2+ is the dominant second messenger in primary sensory neurons. In addition, disrupted Ca2+ signaling is a prominent feature in pain models involving peripheral nerve injury. Standard cytoplasmic Ca2+ recording techniques use high K+ or field stimulation and dissociated neurons. To compare findings in intact dorsal root ganglia, we used a method of simultaneous electrophysiologic and microfluorimetric recording. Methods Dissociated neurons were loaded by bath-applied Fura-2-AM and subjected to field stimulation. Alternatively, we adapted a technique in which neuronal somata of intact ganglia were loaded with Fura-2 through an intracellular microelectrode that provided simultaneous membrane potential recording during activation by action potentials (APs) conducted from attached dorsal roots. Results Field stimulation at levels necessary to activate neurons generated bath pH changes through electrolysis and failed to predictably drive neurons with AP trains. In the intact ganglion technique, single APs produced measurable Ca2+ transients that were fourfold larger in presumed nociceptive C-type neurons than in nonnociceptive A?-type neurons. Unitary Ca2+ transients summated during AP trains, forming transients with amplitudes that were highly dependent on stimulation frequency. Each neuron was tuned to a preferred frequency at which transient amplitude was maximal. Transients predominantly exhibited monoexponential recovery and had sustained plateaus during recovery only with trains of more than 100 APs. Nerve injury decreased Ca2+ transients in C-type neurons, but increased transients in A?-type neurons. Conclusions Refined observation of Ca2+ signaling is possible through natural activation by conducted APs in undissociated sensory neurons and reveals features distinct to neuronal types and injury state. PMID:20526180

  17. The basal ganglia-circa 1982. A review and commentary.

    PubMed

    Mehler, W R

    1981-01-01

    Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's [88] proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's [72] more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement. PMID:6126156

  18. Anatomic study of human laryngeal ganglia: number and distribution.

    PubMed

    Maranillo, Eva; Vazquez, Teresa; Ibanez, Marta; Hurtado, Miguel; Pascual-Font, Aran; McHanwell, Stephen; Valderrama-Canales, Francisco; Sanudo, Jose

    2008-10-01

    We have studied 12 laryngeal nerves: six internal branches of the superior laryngeal nerve (ILN) and six recurrent laryngeal nerves (RLN) from three human adult larynges (two males and one female). After dissection of each individual laryngeal nerve using a surgical microscope, the nerves were preserved in 10% formalin, embedded in paraffin wax, serially sectioned transversely at a thickness of 10 microm and stained with hematoxylin and eosin. We found 2-4 ganglia associated with the ILN. At least two ganglia were always present (six out of six cases), the largest one being associated with the branch of the nerve innervating the vestibule and the smallest one associated with the branch innervating the aryepiglottic fold. Other ganglia were found associated with the branches for the glosso-epiglottic fold and vallecula (four out of six cases) and interarytenoid muscle (three out of six cases). The RLN showed from two to six ganglia, all of them located in its anterior terminal division. Two of the ganglia were located in the part of the nerve between the origin of the branches for the interarytenoid and lateral cricoarytenoid muscles (three out of six cases). The remaining ganglia were located close to or at the origin of the muscular branches innervating the intrinsic laryngeal muscles. The cytology of the ganglia reported suggests that they were all autonomic in nature, probably parasympathetic. PMID:18773473

  19. Convergent evidence for abnormal striatal synaptic plasticity in dystonia

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

    2010-01-01

    Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes linking etiology to pathophysiology of the disease. PMID:20005952

  20. Cooccurrence of Multiple Sclerosis and Idiopathic Basal Ganglia Calcification

    PubMed Central

    Abedini, M.; Karimi, N.; Tabrizi, N.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of central nervous system that affects both white and gray matter. Idiopathic calcification of the basal ganglia is a rare neurodegenerative disorder of unknown cause that is characterized by sporadic or familial brain calcification. Concurrence of multiple sclerosis (MS) and idiopathic basal ganglia calcification (Fahr's disease) is very rare event. In this study, we describe a cooccurrence of idiopathic basal ganglia calcification with multiple sclerosis. The association between this disease and MS is unclear and also maybe probably coincidental. PMID:26351460

  1. The basal ganglia-circa 1982 - A review and commentary

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1981-01-01

    A review is presented of recent studies which utilize new anterograde and retrograde axon transport methods in order to improve knowledge of the projection of the basal ganglia and to clarify their sites of origin. These studies have thrown new light on certain topographic connectional relationships and have revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Also examined are the many new histochemical techniques that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in or interconnecting with the basal ganglia.

  2. [Immunohistochemical detection of rabies virus antigen in the cardiac ganglia of dogs in paraffin sections].

    PubMed

    Feiden, W; Metze, K

    1991-06-01

    The hearts of five naturally infected rabid dogs were studied by immunohistochemistry on paraffin sections using a monoclonal antibody and the peroxidase labelled streptavidin-biotin method to detect rabies ribonucleoprotein. In all cases distinct small granular and ring-shaped antigen deposits were found within the nerve cells of the cardiac ganglia thus reflecting the early centrifugal spread of virus along the pathway of the vagal nerve to the heart. Histologic findings consisted only of single small eosinophilic inclusions in some nerve cell bodies. These findings may be of diagnostic value. PMID:1887438

  3. Segmentation of nerve bundles and ganglia in spine MRI using particle filters.

    PubMed

    Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

    2011-01-01

    Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation. PMID:22003741

  4. Segmentation of Nerve Bundles and Ganglia in Spine MRI Using Particle Filters

    PubMed Central

    Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

    2011-01-01

    Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation. PMID:22003741

  5. Synaptic dimorphism in Onychophoran cephalic ganglia.

    PubMed

    Peña-Contreras, Z; Mendoza-Briceño, R V; Miranda-Contreras, L; Palacios-Prü, E L

    2007-03-01

    The taxonomic location of the Onychophora has been controversial because of their phenotypic and genotypic characteristics, related to both annelids and arthropods. We analyzed the ultrastructure of the neurons and their synapses in the cephalic ganglion of a poorly known invertebrate, the velvet worm Peripatus sedgwicki, from the mountainous region of El Valle, Mérida, Venezuela. Cephalic ganglia were dissected, fixed and processed for transmission electron microscopy. The animal has a high degree of neurobiological development, as evidenced by the presence of asymmetric (excitatory) and symmetric (inhibitory) synapses, as well as the existence of glial cell processes in a wide neuropile zone. The postsynaptic terminals were seen to contain subsynaptic cisterns formed by membranes of smooth endoplasmic reticulum beneath the postsynaptic density, whereas the presynaptic terminal showed numerous electron transparent synaptic vesicles. From the neurophylogenetic perspectives, the ultrastructural characteristics of the central nervous tissue of the Onychophora show important evolutionary acquirements, such as the presence of both excitatory and inhibitory synapses, indicating functional synaptic transmission, and the appearance of mature glial cells. PMID:18457135

  6. Clinical manifestation and neuroimaging methods in diagnosing basal ganglia calcifications.

    PubMed

    Stenc Bradvica, Ivanka; Jan?uljak, Davor; Butkovi?-Soldo, Silva; Mihaljevi?, Ivan; Vladeti?, Mirjana; Bradvica, Mario

    2013-02-01

    The aim of this case study was to evaluate the clinical symptoms in patients with basal ganglia calcifications and compare the neuroimaging methods used in confirming this state. The clinical status and performed transcranial sonography of basal ganglia structures in patients with brain calcifications found by computed brain tomography was examined. In one of these patients DaTSCAN was performed. A large spectrum of different symptoms was found. Transcranial sonography of basal ganglia showed the hyperechogenicity of nucleus lenticularis in eight out of 10 patients. DaTSCAN, which was performed to one patient with parkinsonian signs and the hyperechogenicity of substantia nigra found by transcranial sonography, was normal. Transcranial sonography is a newly neuroimaging method which can contribute to diagnosing basal ganglia calcifications in patients with different neurological signs. Computed tomography of brain remains the most adequate technique in visualising calcifications. PMID:23348181

  7. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

    Chen, Christopher H.; Fremont, Rachel; Arteaga-Bracho, Eduardo E.; Khodakhah, Kamran

    2014-01-01

    The graceful, purposeful motion of our body is an engineering feat which remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. Here we show in mice that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway. Under physiological conditions this short latency pathway is capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition this pathway relays aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  8. Human laryngeal ganglia contain both sympathetic and parasympathetic cell types.

    PubMed

    Ibanez, Marta; Valderrama-Canales, Francisco J; Maranillo, Eva; Vazquez, Teresa; Pascual-Font, Arán; McHanwell, Stephen; Sanudo, Jose

    2010-09-01

    The presence of ganglia associated with the laryngeal nerves is well documented. In man, these ganglia have been less well studied than in other species and, in particular, the cell types within these ganglia are less well characterized. Using a panel of antibodies to a variety of markers found in the paraganglion cells of other species, we were able to show the existence of at least two populations of cells within human laryngeal paraganglia. One population contained chromogranin and tyrosine hydroxylase representing a neurosecretory population possibly secreting dopamine. A second population of choline acetyltransferase positive cells would appear to have a putative parasympathetic function. Further work is needed to characterize these cell populations more fully before it will be possible to assign functions to these cell types but our results are consistent with the postulated functions of these ganglia as chemoreceptors, neurosecretory cells, and regulators of laryngeal mucus secretion. PMID:20821402

  9. Genetics Home Reference: Biotin-thiamine-responsive basal ganglia disease

    MedlinePLUS

    ... disability, and seizures. Severe cases may result in coma and become life-threatening. Typically, the neurological symptoms ... ganglia disease? ataxia ; autosomal ; autosomal recessive ; biotin ; cell ; coma ; deficiency ; disability ; dysphagia ; dystonia ; encephalopathy ; fever ; gene ; hemiparesis ; ...

  10. Alarin in cranial autonomic ganglia of human and rat.

    PubMed

    Schrödl, Falk; Kaser-Eichberger, Alexandra; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Bruckner, Daniela; Krefft, Karolina; Kofler, Barbara; Brandtner, Herwig; Reitsamer, Herbert A

    2015-02-01

    Extrinsic and intrinsic sources of the autonomic nervous system contribute to choroidal innervation, thus being responsible for the control of choroidal blood flow, aqueous humor production or intraocular pressure. Neuropeptides are involved in this autonomic control, and amongst those, alarin has been recently introduced. While alarin is present in intrinsic choroidal neurons, it is not clear if these are the only source of neuronal alarin in the choroid. Therefore, we here screened for the presence of alarin in human cranial autonomic ganglia, and also in rat, a species lacking intrinsic choroidal innervation. Cranial autonomic ganglia (i.e., ciliary, CIL; pterygopalatine, PPG; superior cervical, SCG; trigeminal ganglion, TRI) of human and rat were prepared for immunohistochemistry against murine and human alarin, respectively. Additionally, double staining experiments for alarin and choline acetyltransferase (ChAT), tyrosine hydroxilase (TH), substance P (SP) were performed in human and rat ganglia for unequivocal identification of ganglia. For documentation, confocal laser scanning microscopy was used, while quantitative RT-PCR was applied to confirm immunohistochemical data and to detect alarin mRNA expression. In humans, alarin-like immunoreactivity (alarin-LI) was detected in intrinsic neurons and nerve fibers of the choroidal stroma, but was lacking in CIL, PPG, SCG and TRI. In rat, alarin-LI was detected in only a minority of cranial autonomic ganglia (CIL: 3.5%; PPG: 0.4%; SCG: 1.9%; TRI: 1%). qRT-PCR confirmed the low expression level of alarin mRNA in rat ganglia. Since alarin-LI was absent in human cranial autonomic ganglia, and only present in few neurons of rat cranial autonomic ganglia, we consider it of low impact in extrinsic ocular innervation in those species. Nevertheless, it seems important for intrinsic choroidal innervation in humans, where it could serve as intrinsic choroidal marker. PMID:25497346

  11. Cognitive-motor interactions of the basal ganglia in development

    PubMed Central

    Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

  12. Reassessing Models of Basal Ganglia Function and Dysfunction

    PubMed Central

    Nelson, Alexandra B.; Kreitzer, Anatol C.

    2015-01-01

    The basal ganglia are a series of interconnected subcortical nuclei. The function and dysfunction of these nuclei has been studied intensively as it pertains to motor control, but more recently our knowledge of these functions has broadened to include prominent roles in cognition and affective control. This review will summarize historical models of basal ganglia function, findings which have supported or conflicted with these models, and emphasize recent work in animals and humans directly testing the hypotheses generated by these models. PMID:25032493

  13. Cognitive-motor interactions of the basal ganglia in development.

    PubMed

    Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

  14. Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.

    PubMed

    Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf; Huang, Neng C; Poston, Kathleen L; Bronte-Stewart, Helen M; Schulte, Tilman

    2015-09-01

    Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance. PMID:25280970

  15. Automatic Evaluation of Speech Rhythm Instability and Acceleration in Dysarthrias Associated with Basal Ganglia Dysfunction

    PubMed Central

    Rusz, Jan; Hlavni?ka, Jan; ?mejla, Roman; R?ži?ka, Evžen

    2015-01-01

    Speech rhythm abnormalities are commonly present in patients with different neurodegenerative disorders. These alterations are hypothesized to be a consequence of disruption to the basal ganglia circuitry involving dysfunction of motor planning, programing, and execution, which can be detected by a syllable repetition paradigm. Therefore, the aim of the present study was to design a robust signal processing technique that allows the automatic detection of spectrally distinctive nuclei of syllable vocalizations and to determine speech features that represent rhythm instability (RI) and rhythm acceleration (RA). A further aim was to elucidate specific patterns of dysrhythmia across various neurodegenerative disorders that share disruption of basal ganglia function. Speech samples based on repetition of the syllable /pa/ at a self-determined steady pace were acquired from 109 subjects, including 22 with Parkinson’s disease (PD), 11 progressive supranuclear palsy (PSP), 9 multiple system atrophy (MSA), 24 ephedrone-induced parkinsonism (EP), 20 Huntington’s disease (HD), and 23 healthy controls. Subsequently, an algorithm for the automatic detection of syllables as well as features representing RI and RA were designed. The proposed detection algorithm was able to correctly identify syllables and remove erroneous detections due to excessive inspiration and non-speech sounds with a very high accuracy of 99.6%. Instability of vocal pace performance was observed in PSP, MSA, EP, and HD groups. Significantly increased pace acceleration was observed only in the PD group. Although not significant, a tendency for pace acceleration was observed also in the PSP and MSA groups. Our findings underline the crucial role of the basal ganglia in the execution and maintenance of automatic speech motor sequences. We envisage the current approach to become the first step toward the development of acoustic technologies allowing automated assessment of rhythm in dysarthrias. PMID:26258122

  16. Quantitation of the human basal ganglia with Positron Emission Tomography

    SciTech Connect

    Bendriem, B.; Dewey, S.L.; Schlyer, D.J.; Wolf, A.P.; Volkow, N.D.

    1990-01-01

    The accurate measurement of the concentration of a radioisotope in small structures with PET requires a correction for quantitation loss due to the partial volume effect and the effect of scattered radiation. To evaluate errors associated with measures in the human basal ganglia (BG) we have built a unilateral model of the BG that we have inserted in a 20 cm cylinder. The recovery coefficient (RC = measured activity/true activity) for our BG phantom has been measured on a CTI tomograph (model 931-08/12) with different background concentrations (contrast) and at different axial locations in the gantry. The BG was visualized on 4 or 5 slices depending on its position in the gantry and on the contrast used. The RC was 0.75 with no background (contrast equal to 1.0). Increasing the relative radioactivity concentration in the background increased the RC from 0.75 to 2.00 when the contrast was {minus}0.7 (BG < Background). The RC was also affected by the size and the shape of the region of interest (ROI) used (RC from 0.75 to 0.67 with ROI size from 0.12 to 1.41 cm{sup 2}). These results show that accurate RC correction depends not only on the volume of the structure but also on its contrast with its surroundings as well as on the selection of the ROI. They also demonstrate that the higher the contrast the more sensitive to axial positioning PET measurements in the BG are. These data provide us with some information about the variability of PET measurements in small structure like the BG and we have proposed some strategies to improve the reproducibility. 18 refs., 3 figs., 5 tabs.

  17. Genetic screening and functional characterization of PDGFRB mutations associated with basal ganglia calcification of unknown etiology.

    PubMed

    Sanchez-Contreras, Monica; Baker, Matthew C; Finch, NiCole A; Nicholson, Alexandra; Wojtas, Aleksandra; Wszolek, Zbigniew K; Ross, Owen A; Dickson, Dennis W; Rademakers, Rosa

    2014-08-01

    Three causal genes for idiopathic basal ganglia calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet-derived growth factor receptor family type ?, and PDGFB, encoding PDGF-B, the specific ligand of PDGFR?, were found implicating the PDGF-B/PDGFR? pathway in abnormal brain calcification. In this study, we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFR? and two previously reported mutants, p.L658P and p.R987W PDGFR? in cell culture. We show that, in response to PDGF-BB stimulation, the p.L658P mutation completely suppresses PDGFR? autophosphorylation, whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC. PMID:24796542

  18. Genetic screening and functional characterization of PDGFRB mutations associated with Basal Ganglia Calcification of Unknown Etiology

    PubMed Central

    Sanchez-Contreras, Monica; Baker, Matthew C.; Finch, NiCole A.; Nicholson, Alexandra; Wojtas, Aleksandra; Wszolek, Zbigniew K.; Ross, Owen A.; Dickson, Dennis W.; Rademakers, Rosa

    2014-01-01

    Three causal genes for Idiopathic Basal Ganglia Calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet-derived growth factor receptor family type ?, and PDGFB, encoding PDGF-B, the specific ligand of PDGFR?, were found implicating the PDGF-B/PDGFR? pathway in abnormal brain calcification. In this study we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFR? and two previously reported mutants, p.L658P and p.R987W PDGFR? in cell culture. We show that, in response to PDGF-BB stimulation, the p.L658P mutation completely suppresses PDGFR? autophosphorylation whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC. PMID:24796542

  19. Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia

    PubMed Central

    Stoessl, A. Jon; Lehericy, Stephane; Strafella, Antonio P.

    2015-01-01

    Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson’s disease from healthy controls, and show great promise for differentiation between Parkinson’s disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson’s disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson’s disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression. PMID:24954673

  20. A selective role for right insula—basal ganglia circuits in appetitive stimulus processing

    PubMed Central

    Vijayaraghavan, Lavanya; Adolphs, Ralph; Kennedy, Daniel P.; Cassell, Martin; Tranel, Daniel; Paradiso, Sergio

    2013-01-01

    Hemispheric lateralization of hedonic evaluation (‘liking’) and incentive motivation (‘wanting’) in neural networks connecting the basal ganglia and insula (BG-I) in humans was examined. Participants with brain damage restricted to the BG-I of the right (n = 5) or left (n = 5) hemisphere, and 26 healthy participants matched on age, sex and intelligence quotient were tested on positively and negatively valenced pictures drawn from varied stimulus categories (Vijayaraghavan et al., 2008). Liking was assessed with explicit ratings of pleasantness using a nine-point Likert scale. Wanting was quantified as the amount of work (via repeated keypresses) that participants expended to increase (approach) or decrease (withdraw) viewing time. Right-lesion patients showed abnormally low viewing times and liking ratings for positive images. For a subset of positive images depicting sexual content, right-lesion patients exhibited active withdrawal, while the other two groups approached such stimuli. These results suggest that the right basal ganglia–insula complex plays a greater role than the left in supporting hedonic evaluation and motivational approach to positively valenced stimuli. The finding that active avoidance of stimuli that were not ‘liked’ was spared in both right- and left-sided lesion subjects suggests that unilateral damage to insula/basal ganglia circuits may not be sufficient to affect general incentive motivation independent of preference. PMID:22798397

  1. Expression and localization of aquaporin-4 in sensory ganglia.

    PubMed

    Kato, Jungo; Takai, Yoshiki; Hayashi, Mariko Kato; Kato, Yasuhiro; Tanaka, Manami; Sohma, Yoshiro; Abe, Yoichiro; Yasui, Masato

    2014-09-01

    Aquaporin-4 (AQP4) is a water channel protein that is predominantly expressed in astrocytes in the CNS. The rapid water flux through AQP4 may contribute to electrolyte/water homeostasis and may support neuronal activities in the CNS. On the other hand, little is known about the expression of AQP4 in the peripheral nervous system (PNS). Using AQP4(-/-) mice as a negative control, we demonstrated that AQP4 is also expressed in sensory ganglia, such as trigeminal ganglia and dorsal root ganglia in the PNS. Immunohistochemistry revealed that AQP4 is exclusively localized to satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in the sensory ganglia. Biochemical analyses revealed that the expression levels of AQP4 in sensory ganglia were considerably lower than those in astrocytes in the CNS. Consistently, behavioral analyses did not show any significant difference in terms of mechanical and cold sensitivity between wild type and AQP4(-/-) mice. Overall, although the pathophysiological relevance of AQP4 in somatosensory perception remains unclear, our findings provide new insight into the involvement of water homeostasis in the peripheral sensory system. PMID:25124666

  2. Basal ganglia and Dopamine Contributions to Probabilistic Category Learning

    PubMed Central

    Shohamy, D.; Myers, C.E.; Kalanithi, J.; Gluck, M.A.

    2009-01-01

    Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge. PMID:18061261

  3. Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

    PubMed Central

    Pappas, Samuel S.; Leventhal, Daniel K.; Albin, Roger L.; Dauer, William T.

    2014-01-01

    This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role—Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. PMID:24947237

  4. Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation

    PubMed Central

    Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H.

    2013-01-01

    A typical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). “Neurally impaired” versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands, and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable’s motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

  5. Cell adhesion molecule contactin-associated protein 3 is expressed in the mouse basal ganglia during early postnatal stages.

    PubMed

    Hirata, Haruna; Umemori, Juzoh; Yoshioka, Hiroki; Koide, Tsuyoshi; Watanabe, Kazutada; Shimoda, Yasushi

    2016-01-01

    Cell adhesion molecules play important roles in the development of the nervous system. Among the contactin-associated protein (Caspr; also known as Cntnap) family, which belongs to the neurexin superfamily of proteins, Caspr and Caspr2 are indispensable for the formation and maintenance of myelinated nerves. In contrast, a physiological role for Caspr3 remains to be elucidated. This study examines the expression and localization of Caspr3 in the mouse brain using newly generated Caspr3 antibodies. Caspr3 was expressed abundantly between the first and the second postnatal weeks. During this period, Caspr3 was localized especially to the basal ganglia, including the striatum, external segment of the globus pallidus, and substantia nigra, and no gross abnormalities were apparent in the basal ganglia of Caspr3 knockout mice. In the striatum, Caspr3 was expressed by a subpopulation of medium spiny neurons that constitute the direct and indirect pathways. Caspr3 immunostaining was observed as punctate around the cell bodies as well as in the soma. These Caspr3 signals did not, however, overlap with those of synaptic markers. Our findings suggest that Caspr3 may play an important role in basal ganglia development during early postnatal stages. © 2015 Wiley Periodicals, Inc. PMID:26389685

  6. Oscillations and the basal ganglia: Motor control and beyond

    PubMed Central

    Brittain, John-Stuart; Brown, Peter

    2016-01-01

    Oscillations form a ubiquitous feature of the central nervous system. Evidence is accruing from cortical and sub-cortical recordings that these rhythms may be functionally important, although the precise details of their roles remain unclear. The basal ganglia share this predilection for rhythmic activity which, as we see in Parkinson’s disease, becomes further enhanced in the dopamine depleted state. While certain cortical rhythms appear to penetrate the basal ganglia, others are transformed or blocked. Here, we discuss the functional association of oscillations in the basal ganglia and their relationship with cortical activity. We further explore the neural underpinnings of such oscillatory activity, including the important balance to be struck between facilitating information transmission and limiting information coding capacity. Finally, we introduce the notion that synchronised oscillatory activity can be broadly categorised as immutability promoting rhythms that reinforce incumbent processes, and mutability promoting rhythms that favour novel processing. PMID:23711535

  7. BASAL GANGLIA PATHOLOGY IN SCHIZOPHRENIA: DOPAMINE CONNECTIONS and ANOMALIES

    PubMed Central

    Perez-Costas, Emma; Melendez-Ferro, Miguel; Roberts, Rosalinda C.

    2010-01-01

    Schizophrenia is a severe mental illness that affects 1% of the world population. The disease usually manifests itself in early adulthood with hallucinations, delusions, cognitive and emotional disturbances and disorganized thought and behavior. Dopamine was the first neurotransmitter to be implicated in the disease, and though no longer the only suspect in schizophrenia pathophysiology, it obviously plays an important role. The basal ganglia are the site of most of the dopamine neurons in the brain and the target of antipsychotic drugs. In this review we will start with an overview of basal ganglia anatomy emphasizing dopamine circuitry. Then, we will review the major deficits in dopamine function in schizophrenia, emphasizing the role of excessive dopamine in the basal ganglia and the link to psychosis. PMID:20089137

  8. Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors.

    PubMed

    Espinosa-Medina, I; Outin, E; Picard, C A; Chettouh, Z; Dymecki, S; Consalez, G G; Coppola, E; Brunet, J-F

    2014-07-01

    Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest cells coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b) together with markers of Schwann cell precursors. Some give rise to Schwann cells after down-regulation of PHOX2b. Others form parasympathetic ganglia after being guided to the site of ganglion formation by the nerves that carry preganglionic fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development. PMID:24925912

  9. Rhythmic Cortical Neurons Increase their Oscillations and Sculpt Basal Ganglia Signaling During Motor Learning

    PubMed Central

    Day, Nancy F.; Nick, Teresa A.

    2014-01-01

    The function and modulation of neural circuits underlying motor skill may involve rhythmic oscillations (Feller, 1999; Marder and Goaillard, 2006; Churchland et al., 2012). In the proposed pattern generator for birdsong, the cortical nucleus HVC, the frequency and power of oscillatory bursting during singing increases with development (Crandall et al., 2007; Day et al., 2009). We examined the maturation of cellular activity patterns that underlie these changes. Single unit ensemble recording combined with antidromic identification (Day et al., 2011) was used to study network development in anesthetized zebra finches. Autocovariance quantified oscillations within single units. A subset of neurons oscillated in the theta/alpha/mu/beta range (8–20 Hz), with greater power in adults compared to juveniles. Across the network, the normalized oscillatory power in the 8–20 Hz range was greater in adults than juveniles. In addition, the correlated activity between rhythmic neuron pairs increased with development. We next examined the functional impact of the oscillators on the output neurons of HVC. We found that the firing of oscillatory neurons negatively correlated with the activity of cortico-basal ganglia neurons (HVCXs), which project to Area X (the song basal ganglia). If groups of oscillators work together to tonically inhibit and precisely control the spike timing of adult HVCXs with coordinated release from inhibition, then the activity of HVCXs in juveniles should be decreased relative to adults due to uncorrelated, tonic inhibition. Consistent with this hypothesis, HVCXs had lower activity in juveniles. These data reveal network changes that shape cortical-to-basal ganglia signaling during motor learning. PMID:23776169

  10. 42 CFR 37.54 - Notification of abnormal radiographic findings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other significant abnormal findings... in accordance with section 203 of the Act (see 30 CFR part 90). Positive findings with regard to... shape or size, tuberculosis, cancer, complicated pneumoconiosis, and any other significant...

  11. Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy.

    PubMed

    Vernino, Steven; Hopkins, Steve; Wang, Zhengbei

    2009-03-12

    Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (alpha3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Ganglionic AChR antibodies are found in many patients with autoimmune autonomic ganglionopathy (AAG). These antibodies recognize the alpha3 subunit of the ganglionic AChR, and thus do not bind non-specifically to other nicotinic AChR. Patients with high levels of ganglionic AChR antibodies typically present with rapid onset of severe autonomic failure, with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia gravis, AAG is an antibody-mediated neurological disorder. Antibodies from patients with AAG inhibit ganglionic AChR currents and impair transmission in autonomic ganglia. An animal model of AAG in the rabbit recapitulates the important clinical features of the human disease and provides additional evidence that AAG is an antibody-mediated disorder caused by impairment of synaptic transmission in autonomic ganglia. PMID:18951069

  12. Abnormal Head Position

    MedlinePLUS

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  13. Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

    PubMed

    Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D

    2015-11-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  14. Intracellular recordings from pancreatic ganglia of the cat.

    PubMed Central

    King, B F; Love, J A; Szurszewski, J H

    1989-01-01

    1. The anatomy, morphology, and electrophysiology of parasympathetic ganglia of cat pancreas were studied in vitro. 2. Pancreatic ganglia existed as an interconnected plexus of small ganglia (ten to fifty cells) lying in the interlobular connective tissue. Occasionally smaller ganglia (four to ten cells) were observed lying on or within nerve trunks. 3. Electron micrographs revealed the presence of neurones and satellite cells as well as unmyelinated axons and nerve terminals. Nerve terminals contained small clear vesicles and/or large, dense-cored vesicles. 4. Intracellular recording of electrical activity revealed the presence of two types of ganglion cells. Type I ganglion cells exhibited resting membrane potentials that ranged from -40 to -63 mV and input resistances that ranged from 8 to 168 M omega. They responded to intracellular depolarizing current with action potentials, and received synaptic inputs which when activated caused fast and slow depolarizing responses. Type I cells were considered to be ganglionic neurones. Type II ganglion cells had higher resting membrane potentials that ranged from -61 to -83 mV, lower input resistances that ranged from 5 to 83 M omega and were electrically unexcitable. Repetitive stimulation of preganglionic nerves evoked a slow depolarization that was frequency dependent. Type II cells were considered to be satellite cells. 5. Stimulation of nerve trunks both central and peripheral to the ganglia evoked multiple, subthreshold, fast EPSPs in all type I cells tested. Fast EPSPs were blocked by the nicotinic antagonist hexamethonium. 6. Antidromic potentials were also observed following stimulation of either central or peripheral nerve trunks but never both. 7. In type I cells repetitive stimulation of both central and peripheral nerve trunks resulted in a slow, synaptically mediated depolarization which persisted during superfusion with nicotinic and muscarinic receptor antagonists. 8. Periods of low-frequency, spontaneous fast EPSPs and action potentials were observed in all type I cells tested. 9. It was concluded that parasympathetic neurones in cat pancreatic ganglia receive convergent fast and slow synaptic inputs from central and possibly peripheral sources and may function in vivo as sites of integration. The occurrence of spontaneous synaptic potentials in pancreatic ganglia suggests the possibility of intrinsic neural control of pancreatic function. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:2621634

  15. Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X

    PubMed Central

    Haesler, Sebastian; Rochefort, Christelle; Georgi, Benjamin; Licznerski, Pawel; Osten, Pavel; Scharff, Constance

    2007-01-01

    The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2. PMID:18052609

  16. 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. PMID:25445191

  17. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

    PubMed

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  18. Cerebellar networks with the cerebral cortex and basal ganglia

    PubMed Central

    Bostan, Andreea C.; Dum, Richard P.; Strick, Peter L.

    2013-01-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent results from neuroanatomical, behavioral and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that the output from the cerebellum reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, indicating that the two subcortical structures are part of a densely interconnected network. Altogether, these results provide the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  19. Canceling actions involves a race between basal ganglia pathways

    PubMed Central

    Schmidt, Robert; Leventhal, Daniel K.; Mallet, Nicolas; Chen, Fujun; Berke, Joshua D.

    2013-01-01

    Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return. PMID:23852117

  20. Basal ganglia circuits for reward value-guided behavior

    PubMed Central

    Hikosaka, Okihide; Kim, Hyoung F.; Yasuda, Masaharu; Yamamoto, Shinya

    2014-01-01

    The basal ganglia are equipped with inhibitory and disinhibitory mechanisms that enable to choose valuable objects and actions. Notably, a value can be determined flexibly by recent experience or stably by prolonged experience. Recent studies have revealed that the head and tail of the caudate nucleus selectively and differentially process flexible and stable values of visual objects. These signals are sent to the superior colliculus through different parts of the substantia nigra, so that the animal looks preferentially at high-valued objects, but in different manners. Relying on short-term value memories, the caudate head circuit allows gaze to move expectantly to recently valued objects. Relying on long-term value memories, the caudate tail circuit allows gaze to move automatically to previously valued objects. The basal ganglia also contain an equivalent parallel mechanism for action values. Such flexible-stable parallel mechanisms for object and action values create a highly adaptable system for decision making. PMID:25032497

  1. Basal ganglia iron in tardive dyskinesia: an MRI study.

    PubMed

    Elkashef, A M; Egan, M F; Frank, J A; Hyde, T M; Lewis, B K; Wyatt, R J

    1994-01-01

    Alterations in brain iron could play an important role in the development of tardive dyskinesia in patients receiving neuroleptic medication. To test this hypothesis, magnetic resonance imaging scans of the brain were performed on 21 chronic schizophrenic patients. Ten patients met research diagnostic criteria for persistent tardive dyskinesia, and 11 were free of tardive dyskinesia. All patients had received long-term neuroleptic treatment and were on a stable neuroleptic dose for at least 3 months before scanning. The signal intensity of basal ganglia structures was obtained as a quantitative estimate of brain iron content. No difference was found in the signal intensity ratios between the two groups. This suggests that iron deposition in the basal ganglia, at least as assessed by this measure, does not play a role in the pathophysiology of tardive dyskinesia. PMID:8167198

  2. Centrality of Striatal Cholinergic Transmission in Basal Ganglia Function

    PubMed Central

    Bonsi, Paola; Cuomo, Dario; Martella, Giuseppina; Madeo, Graziella; Schirinzi, Tommaso; Puglisi, Francesca; Ponterio, Giulia; Pisani, Antonio

    2011-01-01

    Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction. Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson's disease and dystonia. Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders. PMID:21344017

  3. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in treating neurodegenerative disorders.

  4. Gene Therapy of the Peripheral Nervous System: Celiac Ganglia.

    PubMed

    Hammond, Bradley; Kreulen, David L

    2016-01-01

    Gene therapy has played an integral role in advancing our understanding of the central nervous system. However, gene therapy techniques have yet to be widely utilized in the peripheral nervous system. Critical targets for gene therapy within the PNS are the neurons in sympathetic ganglia, which are the final pathway to end organs. Thus they are the most specific targets for organ-specific neuron modification. This presents challenges because neurons are not viscerotopically organized within the ganglia and therefore cannot be targeted by their location. However, organ-specific neurons have been identified in sympathetic ganglia of some species and this offers an opportunity for targeting and transducing neurons by way of their target. In fact, alterations in sympathetic neurons have had pathological effects, and transducing organ-specific sympathetic neurons offer an exciting opportunity to selectively modify sympathetic pathology. In this chapter, we describe a method to virally transduce the celiac ganglion (CG), a prevertebral sympathetic ganglion that innervates abdominal organs, with AAV serotypes 1 and 6; thereby, providing a potential avenue to modulate specific subsets of neurons within the celiac ganglion. PMID:26611594

  5. Proactive Selective Response Suppression Is Implemented via the Basal Ganglia

    PubMed Central

    Majid, D. S. Adnan; Cai, Weidong; Corey-Bloom, Jody

    2013-01-01

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway. PMID:23946385

  6. Comprehensive RNA-Seq Expression Analysis of Sensory Ganglia with a Focus on Ion Channels and GPCRs in Trigeminal Ganglia

    PubMed Central

    Manteniotis, Stavros; Lehmann, Ramona; Flegel, Caroline; Vogel, Felix; Hofreuter, Adrian; Schreiner, Benjamin S. P.; Altmüller, Janine; Becker, Christian; Schöbel, Nicole; Hatt, Hanns; Gisselmann, Günter

    2013-01-01

    The specific functions of sensory systems depend on the tissue-specific expression of genes that code for molecular sensor proteins that are necessary for stimulus detection and membrane signaling. Using the Next Generation Sequencing technique (RNA-Seq), we analyzed the complete transcriptome of the trigeminal ganglia (TG) and dorsal root ganglia (DRG) of adult mice. Focusing on genes with an expression level higher than 1 FPKM (fragments per kilobase of transcript per million mapped reads), we detected the expression of 12984 genes in the TG and 13195 in the DRG. To analyze the specific gene expression patterns of the peripheral neuronal tissues, we compared their gene expression profiles with that of the liver, brain, olfactory epithelium, and skeletal muscle. The transcriptome data of the TG and DRG were scanned for virtually all known G-protein-coupled receptors (GPCRs) as well as for ion channels. The expression profile was ranked with regard to the level and specificity for the TG. In total, we detected 106 non-olfactory GPCRs and 33 ion channels that had not been previously described as expressed in the TG. To validate the RNA-Seq data, in situ hybridization experiments were performed for several of the newly detected transcripts. To identify differences in expression profiles between the sensory ganglia, the RNA-Seq data of the TG and DRG were compared. Among the differentially expressed genes (> 1 FPKM), 65 and 117 were expressed at least 10-fold higher in the TG and DRG, respectively. Our transcriptome analysis allows a comprehensive overview of all ion channels and G protein-coupled receptors that are expressed in trigeminal ganglia and provides additional approaches for the investigation of trigeminal sensing as well as for the physiological and pathophysiological mechanisms of pain. PMID:24260241

  7. Urine - abnormal color

    MedlinePLUS

    The usual color of urine is straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. ... Abnormal urine color may be caused by infection, disease, medicines, or food you eat. Cloudy or milky urine is a sign ...

  8. Skeletal limb abnormalities

    MedlinePLUS

    Skeletal limb abnormalities refers to a variety of bone structure problems in the arms or legs (limbs). ... The term skeletal limb abnormalities is most often used to describe defects in the legs or arms that are due to a problem with your ...

  9. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  10. Coronary disease, cardioneuropathy, and conduction system abnormalities in the cardiomyopathy of Friedreich's ataxia.

    PubMed Central

    James, T N; Cobbs, B W; Coghlan, H C; McCoy, W C; Fisch, C

    1987-01-01

    Abnormalities of the heart are a frequent and possibly ubiquitous problem in patients with Friedreich's ataxia, but their pathogenesis is unclear. Postmortem findings are reported from the hearts of three patients with Friedreich's ataxia who died of congestive heart failure and atrial arrhythmias. Particular attention was paid to the following: the large and small coronary arteries, the nerves and ganglia, the conduction system, and the histological and cellular features of the cardiomyopathy. There were pleomorphic nuclei and focal fibrosis and degeneration throughout each heart including the conduction system. There were distinctive abnormalities of both large and small coronary arteries, and focal degeneration of nerves and ganglia. These observations suggest a mosaic concept for the pathogenesis for the cardiomyopathy of Friedreich's ataxia that involves the interplay of molecular faults, cardiomyopathy, cardioneuropathy, and coronary disease. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 PMID:3593615

  11. Hypomyelination with atrophy of the basal ganglia and cerebellum: further delineation of the phenotype and genotype–phenotype correlation

    PubMed Central

    Hamilton, Eline M.; Polder, Emiel; Vanderver, Adeline; Naidu, Sakkubai; Schiffmann, Raphael; Fisher, Kate; Raguž, Ana Boban; Blumkin, Luba; van Berkel, Carola G. M.; Waisfisz, Quinten; Simons, Cas; Taft, Ryan J.; Abbink, Truus E. M.; Wolf, Nicole I.

    2014-01-01

    Hypomyelination with atrophy of the basal ganglia and cerebellum is a rare leukoencephalopathy that was identified using magnetic resonance imaging in 2002. In 2013, whole exome sequencing of 11 patients with the disease revealed that they all had the same de novo mutation in TUBB4A, which encodes tubulin ?-4A. We investigated the mutation spectrum in a cohort of 42 patients and the relationship between genotype and phenotype. Patients were selected on the basis of clinical and magnetic resonance imaging abnormalities that are indicative of hypomyelination with atrophy of the basal ganglia and cerebellum. Genetic testing and a clinical inventory were performed, and sequential magnetic resonance images were evaluated using a standard protocol. The heterozygous TUBB4A mutation observed in the first 11 patients was the most common (25 patients). Additionally, 13 other heterozygous mutations were identified, located in different structural domains of tubulin ?-4A. We confirmed that the mutations were de novo in all but three patients. In two of these three cases we lacked parental DNA and in one the mutation was also found in the mother, most likely due to mosaicism. Patients showed a phenotypic continuum ranging from neonatal to childhood disease onset, normal to delayed early development and slow to more rapid neurological deterioration. Neurological symptomatology consisted of extrapyramidal movement abnormalities, spasticity, ataxia, cognitive deficit and sometimes epilepsy. Three patients died and the oldest living patient was 29 years of age. The patients’ magnetic resonance images showed an absent or disappearing putamen, variable cerebellar atrophy and highly variable cerebral atrophy. Apart from hypomyelination, myelin loss was evident in several cases. Three severely affected patients had similar, somewhat atypical magnetic resonance image abnormalities. The study results were strongly suggestive of a genotype–phenotype correlation. The 25 patients with the common c.745G>A mutation generally had a less rapidly progressive disease course than the 17 cases with other TUBB4A mutations. Overall, this work demonstrates that the distinctive magnetic resonance imaging pattern for hypomyelination with atrophy of the basal ganglia and cerebellum defines a homogeneous clinical phenotype of variable severity. Patients almost invariably have prominent extrapyramidal movement abnormalities, which are rarely seen in patients with hypomyelination of different origin. A dominant TUBB4A mutation is also associated with dystonia type 4, in which magnetic resonance images of the brain seem normal. It is highly likely that there is a disease continuum associated with TUBB4A mutations, of which hypomyelination with atrophy of the basal ganglia and cerebellum and dystonia type 4 are the extremes. This would indicate that extrapyramidal movement abnormalities constitute the core feature of the disease spectrum related to dominant TUBB4A mutations and that all other features are variable. PMID:24785942

  12. Chromosomal abnormalities in oocytes.

    PubMed

    Plachot, M

    2001-10-22

    Since the beginning of in vitro fertilization (IVF), basic research has provided insight in the field of human reproduction, especially in genetics. Indeed, the contribution of chromosomal abnormalities to oocyte disorders and impaired embryonic development is now well known. Of oocytes that fail to fertilize after in vitro insemination, 26.5% have been found to be abnormal, with 13.3% showing hypohaploidy, 8.1% hyperhaploidy, 1.6% structural abnormalities and 3.5% diploidy. The total incidence of abnormalities seems to be correlated with the fertility status of the woman. It is higher in oocytes from women with tubal or unexplained infertility than in those from women whose husband's infertility is the sole cause of infertility in the couple. Although few oocytes recovered during natural cycles have been studied, gonadotropins, which are widely used to stimulate follicle growth and ovulation, do not increase the risk of abnormalities. The effect of maternal age on fetal aneuploidy, well documented at birth, has not been unambiguously shown to result from an increase in the frequency of aneuploid oocytes. Intra- and extra-follicular influences (perifollicular microvasculature, oxygenation, and the presence of residues from cigarette smoke) may disturb maturation, leading to immaturity and aneuploidy. Thus, oocyte meiosis is very sensitive to endogenous and exogenous factors that could result in oocytes with chromosomal abnormalities and therefore, abnormal zygotes. PMID:11576735

  13. Purification and culture of adult rat dorsal root ganglia neurons.

    PubMed

    Delree, P; Leprince, P; Schoenen, J; Moonen, G

    1989-06-01

    To study the trophic requirements of adult rat dorsal root ganglia neurons (DRG) in vitro, we developed a purification procedure that yields highly enriched neuronal cultures. Forty to fifty ganglia are dissected from the spinal column of an adult rat. After enzymatic and mechanical dissociation of the ganglia, myelin debris are eliminated by centrifugation on a Percoll gradient. The resulting cell suspension is layered onto a nylon mesh with a pore size of 10 microns. Most of the neurons, the diameter of which ranged from 17 microns to greater than 100 microns, are retained on the upper surface of the sieve; most of the non-neuronal cells with a caliber of less than 10 microns after trypsinization go through it. Recovery of neurons is achieved by reversing the mesh onto a Petri dish containing culture medium. Neurons to non-neurons ratio is 1 to 10 in the initial cell suspension and 1 to 1 after separation. When these purified neurons are seeded at a density of 3,000 neurons/cm2 in 6 mm polyornithine-laminin (PORN-LAM) coated wells, neuronal survival (assessed by the ability to extend neurites), measured after 48 hr of culture, is very low (from 0 to 16%). Addition of nerve growth factor (NGF) does not improve neuronal survival. However, when neurons are cultured in the presence of medium conditioned (CM) by astrocytes or Schwann cells, 60-80% of the seeded, dye-excluding neurons survive. So, purified adult DRG neurons require for their short-term survival and regeneration in culture, a trophic support that is present in conditioned medium from PNS or CNS glia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2754765

  14. [Plexiform neurofibroma and basal ganglia anomaly in Watson syndrome].

    PubMed

    Weber, P; Kotthoff, S; Schuierer, G; Kurlemann, G

    1999-01-01

    A 4 year-old boy was referred for diagnostic reevaluation with known pulmonary valve stenosis. Physical examination revealed multiple cafe-au-lait spots, inguinal freckling and on the right side in supraclavicular region a softly, non-painful tumour. The boy showed a mild mental and language retardation. Ultrasound and MRT demonstrated supraclavicular a plexiform neurofibroma and intracranial increased intensity lesions in basal ganglia and mesencephalon. In our patient, we have diagnosed a Watson-Syndrome, the overlap and differences to neurofibromatosis type I is discussed. PMID:10412128

  15. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    SciTech Connect

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H. ); Murray, R.S. Veterans Administration Medical Center, Denver, CO )

    1988-04-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia.

  16. Abnormal Uterine Bleeding

    MedlinePLUS

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  17. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  18. Aplysia Ganglia Preparation for Electrophysiological and Molecular Analyses of Single Neurons

    PubMed Central

    Akhmedov, Komol; Kadakkuzha, Beena M.; Puthanveettil, Sathyanarayanan V.

    2014-01-01

    A major challenge in neurobiology is to understand the molecular underpinnings of neural circuitry that govern a specific behavior. Once the specific molecular mechanisms are identified, new therapeutic strategies can be developed to treat abnormalities in specific behaviors caused by degenerative diseases or aging of the nervous system. The marine snail Aplysia californica is well suited for the investigations of cellular and molecular basis of behavior because neural circuitry underlying a specific behavior could be easily determined and the individual components of the circuitry could be easily manipulated. These advantages of Aplysia have led to several fundamental discoveries of neurobiology of learning and memory. Here we describe a preparation of the Aplysia nervous system for the electrophysiological and molecular analyses of individual neurons. Briefly, ganglion dissected from the nervous system is exposed to protease to remove the ganglion sheath such that neurons are exposed but retain neuronal activity as in the intact animal. This preparation is used to carry out electrophysiological measurements of single or multiple neurons. Importantly, following the recording using a simple methodology, the neurons could be isolated directly from the ganglia for gene expression analysis. These protocols were used to carry out simultaneous electrophysiological recordings from L7 and R15 neurons, study their response to acetylcholine and quantitating expression of CREB1 gene in isolated single L7, L11, R15, and R2 neurons of Aplysia. PMID:24457225

  19. Interaction between basal ganglia and limbic circuits in learning and memory processes.

    PubMed

    Calabresi, Paolo; Picconi, Barbara; Tozzi, Alessandro; Ghiglieri, Veronica

    2016-01-01

    Hippocampus and striatum play distinctive roles in memory processes since declarative and non-declarative memory systems may act independently. However, hippocampus and striatum can also be engaged to function in parallel as part of a dynamic system to integrate previous experience and adjust behavioral responses. In these structures the formation, storage, and retrieval of memory require a synaptic mechanism that is able to integrate multiple signals and to translate them into persistent molecular traces at both the corticostriatal and hippocampal/limbic synapses. The best cellular candidate for this complex synthesis is represented by long-term potentiation (LTP). A common feature of LTP expressed in these two memory systems is the critical requirement of convergence and coincidence of glutamatergic and dopaminergic inputs to the dendritic spines of the neurons expressing this form of synaptic plasticity. In experimental models of Parkinson's disease abnormal accumulation of α-synuclein affects these two memory systems by altering two major synaptic mechanisms underlying cognitive functions in cholinergic striatal neurons, likely implicated in basal ganglia dependent operative memory, and in the CA1 hippocampal region, playing a central function in episodic/declarative memory processes. PMID:26372625

  20. 42 CFR 37.53 - Notification of abnormal roentgenographic findings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... to the miner by MSHA in accordance with section 203 of the act (see 30 CFR part 90). Positive... findings suggesting, abnormality of cardiac shape or size, tuberculosis, lung cancer, or any...

  1. 42 CFR 37.54 - Notification of abnormal radiographic findings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... shape or size, tuberculosis, lung cancer, or any other significant abnormal findings other than... section 203 of the Act (see 30 CFR part 90). Positive findings with regard to pneumoconiosis will be..., tuberculosis, cancer, complicated pneumoconiosis, and any other significant abnormal findings, NIOSH...

  2. Familial idiopathic basal ganglia calcification (Fahr’s disease)

    PubMed Central

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.

    2014-01-01

    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr’s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr’s disease. PMID:24983277

  3. Familial idiopathic basal ganglia calcification (Fahr`s disease).

    PubMed

    Mufaddel, Amir A; Al-Hassani, Ghanem A

    2014-07-01

    Familial idiopathic basal ganglia calcification (Fahr`s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr`s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr`s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr`s disease. PMID:24983277

  4. Monitoring Temperature and Fan Speed Using Ganglia and Winbond Chips

    SciTech Connect

    McCaffrey, Cattie; /SLAC

    2006-09-27

    Effective monitoring is essential to keep a large group of machines, like the ones at Stanford Linear Accelerator Center (SLAC), up and running. SLAC currently uses Ganglia Monitoring System to observe about 2000 machines, analyzing metrics like CPU usage and I/O rate. However, metrics essential to machine hardware health, such as temperature and fan speed, are not being monitored. Many machines have a Winbond w83782d chip which monitors three temperatures, two of which come from dual CPUs, and returns the information when the sensor command is invoked. Ganglia also provides a feature, gmetric, that allows the users to monitor their own metrics and incorporate them into the monitoring system. The programming language Perl is chosen to implement a script that invokes the sensors command, extracts the temperature and fan speed information, and calls gmetric with the appropriate arguments. Two machines were used to test the script; the two CPUs on each machine run at about 65 Celsius, which is well within the operating temperature range (The maximum safe temperature range is 77-82 Celsius for the Pentium III processors being used). Installing the script on all machines with a Winbond w83782d chip allows the SLAC Scientific Computing and Computing Services group (SCCS) to better evaluate current cooling methods.

  5. Expression of serotonin receptor genes in cranial ganglia.

    PubMed

    Maeda, Naohiro; Ohmoto, Makoto; Yamamoto, Kurumi; Kurokawa, Azusa; Narukawa, Masataka; Ishimaru, Yoshiro; Misaka, Takumi; Matsumoto, Ichiro; Abe, Keiko

    2016-03-23

    Taste cells release neurotransmitters to gustatory neurons to transmit chemical information they received. Sweet, umami, and bitter taste cells use ATP as a neurotransmitter. However, ATP release from sour taste cells has not been observed so far. Instead, they release serotonin when they are activated by sour/acid stimuli. Thus it is still controversial whether sour taste cells use ATP, serotonin, or both. By reverse transcription-polymerase chain reaction and subsequent in situ hybridization (ISH) analyses, we revealed that of 14 serotonin receptor genes only 5-HT3A and 5-HT3B showed significant/clear signals in a subset of neurons of cranial sensory ganglia in which gustatory neurons reside. Double-fluorescent labeling analyses of ISH for serotonin receptor genes with wheat germ agglutinin (WGA) in cranial sensory ganglia of pkd1l3-WGA mice whose sour neural pathway is visualized by the distribution of WGA originating from sour taste cells in the posterior region of the tongue revealed that WGA-positive cranial sensory neurons rarely express either of serotonin receptor gene. These results suggest that serotonin receptors expressed in cranial sensory neurons do not play any role as neurotransmitter receptor from sour taste cells. PMID:26854841

  6. Congenital bronchial abnormalities revisited.

    PubMed

    Ghaye, B; Szapiro, D; Fanchamps, J M; Dondelinger, R F

    2001-01-01

    Bronchial anatomy is adequately demonstrated with the appropriate spiral computed tomographic technique on cross-sectional images, multiplanar reconstruction images, and three-dimensional reconstruction images. Contrary to the numerous variations of lobar or segmental bronchial subdivisions, abnormal bronchi originating from the trachea or main bronchi are rare. Major bronchial abnormalities include accessory cardiac bronchus (ACB) and "tracheal" bronchus. An ACB is a supernumerary bronchus from the inner wall of the right main bronchus or intermediate bronchus that progresses toward the pericardium. Fourteen ACBs were found in 17,500 consecutive patients (frequency, 0.08%). The term tracheal bronchus encompasses a variety of bronchial anomalies originating from the trachea or main bronchus and directed to the upper lobe. In a series of 35 tracheal bronchi, only eight originated from the trachea, three originated from the carina, and 24 originated from the bronchi. Displaced tracheal bronchi (27 of 35) are more frequent than supernumerary tracheal bronchi (eight of 35). Minor bronchial abnormalities include variants of tracheal bronchus, displaced segmental bronchi, and bronchial agenesis. The main embryogenic hypotheses for congenital bronchial abnormalities are the reduction, migration, and selection theories. Knowledge and understanding of congenital bronchial abnormalities may have important implications for diagnosis, bronchoscopy, surgery, brachytherapy, and intubation. PMID:11158647

  7. [Walking abnormalities in children].

    PubMed

    Segawa, Masaya

    2010-11-01

    Walking is a spontaneous movement termed locomotion that is promoted by activation of antigravity muscles by serotonergic (5HT) neurons. Development of antigravity activity follows 3 developmental epochs of the sleep-wake (S-W) cycle and is modulated by particular 5HT neurons in each epoch. Activation of antigravity activities occurs in the first epoch (around the age of 3 to 4 months) as restriction of atonia in rapid eye movement (REM) stage and development of circadian S-W cycle. These activities strengthen in the second epoch, with modulation of day-time sleep and induction of crawling around the age of 8 months and induction of walking by 1 year. Around the age of 1 year 6 months, absence of guarded walking and interlimb cordination is observed along with modulation of day-time sleep to once in the afternoon. Bipedal walking in upright position occurs in the third epoch, with development of a biphasic S-W cycle by the age of 4-5 years. Patients with infantile autism (IA), Rett syndrome (RTT), or Tourette syndrome (TS) show failure in the development of the first, second, or third epoch, respectively. Patients with IA fail to develop interlimb coordination; those with RTT, crawling and walking; and those with TS, walking in upright posture. Basic pathophysiology underlying these condition is failure in restricting atonia in REM stage; this induces dysfunction of the pedunculopontine nucleus and consequently dys- or hypofunction of the dopamine (DA) neurons. DA hypofunction in the developing brain, associated with compensatory upward regulation of the DA receptors causes psychobehavioral disorders in infancy (IA), failure in synaptogenesis in the frontal cortex and functional development of the motor and associate cortexes in late infancy through the basal ganglia (RTT), and failure in functional development of the prefrontal cortex through the basal ganglia (TS). Further, locomotion failure in early childhood causes failure in development of functional specialization of the cortex through the spinal stepping generator-fastigial nucleus-thalamus-cortex pathway. Early detection of locomotion failure and early adjustment of this condition through environmental factors can prevent the development of higher cortical dysfunction. PMID:21068458

  8. Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal

    ERIC Educational Resources Information Center

    Shohamy, Daphna; Myers, Catherine E.; Hopkins, Ramona O.; Sage, Jake; Gluck, Mark A.

    2009-01-01

    The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning--the ability to adaptively change a response when…

  9. Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal

    ERIC Educational Resources Information Center

    Shohamy, Daphna; Myers, Catherine E.; Hopkins, Ramona O.; Sage, Jake; Gluck, Mark A.

    2009-01-01

    The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning--the ability to adaptively change a response when…

  10. [Neurobiology of parkinsonism. I. Neural substrates an neurochemistry of the basal ganglia].

    PubMed

    Ponzoni, S; Garcia-Cairasco, N

    1995-09-01

    Movement disorders, in general, are characterized by a breakdown in the integrated coordination of posture and motion by multiple brain and muscular systems. In the expression of parkinsonism, in particular, critical and altered structures such as substantia nigra, appear to be related to the cortex-basal ganglia and thalamus-basal ganglia sub-circuits. PMID:8585835

  11. Cerebral abnormalities: use of calculated T1 and T2 magnetic resonance images for diagnosis

    SciTech Connect

    Mills, C.M.; Crooks, L.E.; Kaufman, L.; Brant-Zawadzki, M.

    1984-01-01

    The potential clinical importance of T1 and T2 relaxation times in distinguishing normal and pathologic tissue with magnetic resonance (MR) is discussed and clinical examples of cerebral abnormalities are given. Five patients with cerebral infarction, 15 with multiple sclerosis, two with Wilson disease, and four with tumors were imaged. Hemorrhagic and ischemic cerebrovascular accidents were distinguished using the spin echo technique. In the patients with multiple sclerosis, lesions had prolonged T1 and T2 times, but the definition of plaque was limited by spatial resolution. No abnormalities in signal intensity were seen in the patient with Wilson disease who was no longer severly disabled; abnormal increased signal intensity in the basal ganglia was found in the second patient with Wilson disease. Four tumors produced abnormal T1 and T2 relaxation times but these values alone were not sufficient for tumor characterization.

  12. Models of Abnormal Scarring

    PubMed Central

    Seo, Bommie F.; Lee, Jun Yong; Jung, Sung-No

    2013-01-01

    Keloids and hypertrophic scars are thick, raised dermal scars, caused by derailing of the normal scarring process. Extensive research on such abnormal scarring has been done; however, these being refractory disorders specific to humans, it has been difficult to establish a universal animal model. A wide variety of animal models have been used. These include the athymic mouse, rats, rabbits, and pigs. Although these models have provided valuable insight into abnormal scarring, there is currently still no ideal model. This paper reviews the models that have been developed. PMID:24078916

  13. Abnormal trigeminal sensory processing in obese mice.

    PubMed

    Rossi, Heather L; Broadhurst, Kimberly A; Luu, Anthony S K; Lara, Orlando; Kothari, Sunny D; Mohapatra, Durga P; Recober, Ana

    2016-01-01

    Obesity is associated with several pain disorders including headache. The effects of obesity on the trigeminal nociceptive system, which mediates headache, remain unknown. We used 2 complementary mouse models of obesity (high-fat diet and leptin deficiency) to examine this. We assessed capsaicin-induced nocifensive behavior and photophobia in obese and control mice. Calcium imaging was used to determine the effects of obesity on the activity of primary trigeminal afferents in vitro. We found that obese mice had a normal acute response to a facial injection of capsaicin, but they developed photophobic behavior at doses that had no effect on control mice. We observed higher calcium influx in cultured trigeminal ganglia neurons from obese mice and a higher percentage of medium to large diameter capsaicin-responsive cells. These findings demonstrate that obesity results in functional changes in the trigeminal system that may contribute to abnormal sensory processing. Our findings provide the foundation for in-depth studies to improve the understanding of the effects of obesity on the trigeminal system and may have implications for the pathophysiology of headache disorders. PMID:26397933

  14. Motor Control Abnormalities in Parkinson’s Disease

    PubMed Central

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  15. Spontaneous Association of Glial Cells With Regrowing Neurites in Mixed Cultures of Dissociated Spiral Ganglia

    PubMed Central

    Whitlon, Donna S.; Tieu, David; Grover, Mary; Reilly, Brian; Coulson, May T.

    2010-01-01

    Evidence from developmental and regeneration studies of the cochlea and other tissues give reason to hypothesize a role for non-neural cells in the growth and regeneration of cochlear spiral ganglion nerve fibers. We examined the spontaneous associations of regrowing neurites and non-neural cells in mixed cultures of dissociated newborn mouse spiral ganglia. After 7 days in vitro, non-neural cells formed a confluent layer in the culture well. Regrowing neurites grew atop this layer, forming non-uniform patterns that were similar to those formed by endogenously expressed laminin-1, entactin and integrin ?4, but not fibronectin or tenascin. In cultures grown for 42 hours and maintained in three different growth media, all regrowing neurites were preferentially associated with spindle-shaped non-neural cells. The spindle shaped cells incorporated BrdU in culture and were immunoreactive for the proteins S100, laminin-1, laminin-2, Sox10, P75 and connexin29 but negative for fibronectin and GFAP. These cells existed in the culture within a much larger, general population of fibronectin positive cells. Immunolabeling of fixed cochleas from neonatal mice localized Sox10, P75 and connexin29, to peripheral nerve bundles. The observed expressions of protein markers and the bipolar, spindle shape of the neurite-associated cells indicates that they are derived in vitro from the original Schwann or satellite cells in the ganglion or spiral lamina. The spontaneous and preferential association of neurites in culture with mitotic Schwann cells highlights the potential contribution neurite-Schwann cell interactions may have in promoting the growth and regrowth of damaged spiral ganglion neurons in the cochlea. PMID:19324078

  16. Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia.

    PubMed

    Imboden, Hans; Patil, Jaspal; Nussberger, Juerg; Nicoud, Françoise; Hess, Benno; Ahmed, Nermin; Schaffner, Thomas; Wellner, Maren; Müller, Dominik; Inagami, Tadashi; Senbonmatsu, Takaaki; Pavel, Jaroslav; Saavedra, Juan M

    2009-04-10

    To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples. Cathepsin D was detected in the rat trigeminal ganglia indicating the possibility of existence of pathways alternative to renin for Ang I formation. In situ hybridization in rat trigeminal ganglia revealed expression of Ang-N mRNA in the cytoplasm of numerous neurons. By using immunocytochemistry, a number of neurons and their processes in both the rat and human trigeminal ganglia were stained for Ang II. Post in situ hybridization immunocytochemistry reveals that in the rat trigeminal ganglia some, but not all Ang-N mRNA-positive neurons marked for Ang II. In some neurons Substance P was found colocalized with Ang II. Angiotensins from rat trigeminal ganglia were quantitated by radioimmunoassay with and without prior separation by high performance liquid chromatography. Immunoreactive angiotensin II (ir-Ang II) was consistently present and the sum of true Ang II (1-8) octapeptide and its specifically measured metabolites were found to account for it. Radioimmunological and immunocytochemical evidence of ir-Ang II in neuronal tissue is compatible with Ang II as a neurotransmitter. In conclusion, these results suggest that Ang II could be produced locally in the neurons of rat trigeminal ganglia. The localization and colocalization of neuronal Ang II with Substance P in the trigeminal ganglia neurons may be the basis for a participation and function of Ang II in the regulation of nociception and migraine pathology. PMID:19323983

  17. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

    PubMed Central

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

    2015-01-01

    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr's disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly presents with mental damage, convulsion, parkinson-like clinical picture, and neuropsychiatric behavior disorders; however, presentation with impulse control disorder is not a frequent presentation. In the current report, a 43-year-old male patient who has been admitted to psychiatry policlinic with the complaints of aggressive behavior episodes and who has been diagnosed with impulse control disorder and IBGC was evaluated in the light of the literature. PMID:26246920

  18. Basal ganglia output to the thalamus: still a paradox

    PubMed Central

    Farries, Michael A.; Fee, Michale S.

    2013-01-01

    The basal ganglia (BG) recipient thalamus controls motor output but it remains unclear how its activity is regulated. Several studies report that thalamic activation occurs via disinhibition during pauses in the firing of inhibitory pallidal inputs from the BG. Other studies indicate that thalamic spiking is triggered by pallidal inputs via post-inhibitory ‘rebound’ calcium spikes. Finally excitatory cortical inputs can drive thalamic activity, which becomes entrained, or time-locked, to pallidal spikes. We present a unifying framework where these seemingly distinct results arise from a continuum of thalamic firing ‘modes’ controlled by excitatory inputs. We provide a mechanistic explanation for paradoxical pallidothalamic coactivations observed during behavior and raise new questions of what information is integrated in the thalamus to control behavior. PMID:24188636

  19. Congenital midface abnormalities.

    PubMed

    Baxter, Daniel J G; Shroff, Manohar

    2011-08-01

    There are a wide variety of congenital midface abnormalities that originate during transformation of the first pair of pharyngeal arches into adult structures. Computed tomography and magnetic resonance imaging are important components in the comprehensive evaluation of these lesions. A detailed understanding of midface embryogenesis and developmental anatomy is important in directing appropriate patient management. PMID:21807312

  20. Neural code alterations and abnormal time patterns in Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Andres, Daniela Sabrina; Cerquetti, Daniel; Merello, Marcelo

    2015-04-01

    Objective. The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson’s disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. Approach. We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. Main results. At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson’s disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. Significance. We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson’s disease.

  1. Parallel basal ganglia circuits for voluntary and automatic behaviour to reach rewards.

    PubMed

    Kim, Hyoung F; Hikosaka, Okihide

    2015-07-01

    The basal ganglia control body movements, value processing and decision-making. Many studies have shown that the inputs and outputs of each basal ganglia structure are topographically organized, which suggests that the basal ganglia consist of separate circuits that serve distinct functions. A notable example is the circuits that originate from the rostral (head) and caudal (tail) regions of the caudate nucleus, both of which target the superior colliculus. These two caudate regions encode the reward values of visual objects differently: flexible (short-term) values by the caudate head and stable (long-term) values by the caudate tail. These value signals in the caudate guide the orienting of gaze differently: voluntary saccades by the caudate head circuit and automatic saccades by the caudate tail circuit. Moreover, separate groups of dopamine neurons innervate the caudate head and tail and may selectively guide the flexible and stable learning/memory in the caudate regions. Studies focusing on manual handling of objects also suggest that rostrocaudally separated circuits in the basal ganglia control the action differently. These results suggest that the basal ganglia contain parallel circuits for two steps of goal-directed behaviour: finding valuable objects and manipulating the valuable objects. These parallel circuits may underlie voluntary behaviour and automatic skills, enabling animals (including humans) to adapt to both volatile and stable environments. This understanding of the functions and mechanisms of the basal ganglia parallel circuits may inform the differential diagnosis and treatment of basal ganglia disorders. PMID:25981958

  2. Pathways for control of face and neck musculature by the basal ganglia and cerebellum.

    PubMed

    Pong, Milton; Horn, Kris M; Gibson, Alan R

    2008-08-01

    The basal ganglia are believed to influence movement via thalamo-cortical projections. However, the basal ganglia may also affect brainstem areas involved in movement control such as the red nucleus. The red nucleus receives input from the cerebellum and projects to motor neurons and premotor neurons in the contralateral brainstem and spinal cord. Are there pathways that allow output from the basal ganglia to influence processing in the red nucleus? This study uses the bidirectional tracer, WGA-HRP, to demonstrate that regions of the cat red nucleus receive input from the basal ganglia as well as from the cerebellum. Output from the entopeduncular nucleus, the feline equivalent of the internal segment of the globus pallidus, provides a modest direct input to the red nucleus as well as a more substantial indirect input via projections to the zona incerta and the fields of Forel. Regions of the red nucleus with input from the basal ganglia also receive input from the cerebellar dentate nucleus and lateral regions of interpositus. The regions of the red nucleus receiving basal gangliar input project to the contralateral facial nucleus and upper segments of the cervical spinal cord. Therefore, the red nucleus provides a junction where output from the basal ganglia can interact with output of the cerebellum for movement control of the head and face. The pathway may provide a substrate for a variety of movement disorders that are seen with diseases of the basal ganglia such as cervical dystonia and Parkinson's facies. PMID:18199482

  3. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed. PMID:25903257

  4. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  5. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  6. Anatomical Abnormalities in Autism?

    PubMed

    Haar, Shlomi; Berman, Sigal; Behrmann, Marlene; Dinstein, Ilan

    2016-04-01

    Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old. PMID:25316335

  7. Frequency and Abundance of Alphaherpesvirus DNA in Human Thoracic Sympathetic Ganglia

    PubMed Central

    Rempel, April; Huntington, Jonathon; Kim, Forrest; Choe, Alexander; Gilden, Don

    2014-01-01

    Alphaherpesvirus reactivation from thoracic sympathetic ganglia (TSG) and transaxonal spread to target organs cause human visceral disease. Yet alphaherpesvirus latency in TSG has not been well characterized. In this study, quantitative PCR detected varicella-zoster virus (VZV), herpes simplex virus 1 (HSV-1), and HSV-2 DNA in 117 fresh TSG obtained postmortem from 15 subjects. VZV DNA was found in 76 (65%) ganglia from all subjects, HSV-1 DNA was found in 5 (4%) ganglia from 3 subjects, and no HSV-2 was found. PMID:24789785

  8. Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia

    PubMed Central

    Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

    2015-01-01

    Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

  9. Case study: acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy.

    PubMed

    Giedd, J N; Rapoport, J L; Leonard, H L; Richter, D; Swedo, S E

    1996-07-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAs) may arise when antibodies directed against invading bacteria cross-react with basal ganglia structures, resulting in exacerbations of obsessive-compulsive disorder (OCD) or tic disorders. This is a report of severe worsening of obsessive-compulsive symptoms in an adolescent boy following infection with group A beta-hemolytic streptococci for whom serial magnetic resonance imaging scans of the brain were acquired to assess the relationship between basal ganglia size, symptom severity, and treatment with plasmapheresis. These data provide further support for basal ganglia-mediated dysfunction in OCD and the potential for immunological treatments in PANDAs patients. PMID:8768351

  10. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  11. Basal ganglia group II metabotropic glutamate receptors specific binding in non-human primate model of L-Dopa-induced dyskinesias.

    PubMed

    Samadi, Pershia; Grégoire, Laurent; Morissette, Marc; Calon, Fréderic; Hadj Tahar, Abdallah; Bélanger, Nancy; Dridi, Mehdi; Bédard, Paul J; Di Paolo, Thérèse

    2008-02-01

    L-Dopa-induced dyskinesias (LIDs), the disabling abnormal involuntary movements induced by chronic use of L-Dopa, limit the quality of life in Parkinson's disease (PD) patients. Modulation of group II metabotropic glutamate receptors (mGluR2/3) in the basal ganglia, a brain region critically involved in motor control, is considered as an alternative approach in therapy of PD. In this study, receptor binding autoradiography of [3H]LY341495, a mGluR2/3 selective radioligand, was used to investigate possible changes in mGluR2/3 in the basal ganglia of L-Dopa-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys having developed LIDs compared to animals in which LIDs were prevented by adjunct treatments with CI-1041, a selective antagonist of the NR1A/2B subtype of NMDA receptor, or low doses of the dopamine D2 receptor agonist, cabergoline. Our study is the first to provide evidence of: (1) the similar localization of [3H]LY341495 specific binding to mGluR2/3 in the primate basal ganglia as compared to receptor distribution measured by immunohistochemistry in human and rat as well as this ligand binding in intact rat brain; (2) no change of [3H]LY341495 specific binding in basal ganglia after nigrostriatal denervation by MPTP; and (3) a widespread reduction of [(3)H]LY341495 specific binding to mGluR2/3 in the caudate nucleus (-17% to -31%), putamen (-12% to -45%) and globus pallidus (-56 to -59%) of non-dyskinetic animals treated with L-Dopa+cabergoline as compared to controls, MPTP monkeys treated with saline, L-Dopa alone (dyskinetic) or L-Dopa+CI-1041 (non-dyskinetic). This study is the first to propose a close interaction between mGluR2/3 and dopamine D2 receptors activation in the basal ganglia. PMID:18001807

  12. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  13. Abnormal Bursting as a Pathophysiological Mechanism in Parkinson's Disease

    PubMed Central

    Lobb, CJ

    2014-01-01

    Despite remarkable advances in Parkinson's disease (PD) research, the pathophysiological mechanisms causing motor dysfunction remain unclear, possibly delaying the advent of new and improved therapies. Several such mechanisms have been proposed including changes in neuronal firing rates, the emergence of pathological oscillatory activity, increased neural synchronization, and abnormal bursting. This review focuses specifically on the role of abnormal bursting of basal ganglia neurons in PD, where a burst is a physiologically-relevant, transient increase in neuronal firing over some reference period or activity. After reviewing current methods for how bursts are detected and what the functional role of bursts may be under normal conditions, existing studies are reviewed that suggest that bursting is abnormally increased in PD and that this increases with worsening disease. Finally, the influence of therapeutic approaches for PD such as dopamine-replacement therapy with levodopa or dopamine agonists, lesions, or deep brain stimulation on bursting is discussed. Although there is insufficient evidence to conclude that increased bursting causes motor dysfunction in PD, current evidence suggests that targeted investigations into the role of bursting in PD may be warranted. PMID:24729952

  14. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  15. Basal Ganglia Outputs Map Instantaneous Position Coordinates during Behavior

    PubMed Central

    Barter, Joseph W.; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A.; Bartholomew, Ryan A.

    2015-01-01

    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions. PMID:25673860

  16. Basal ganglia neurons dynamically facilitate exploration during associative learning.

    PubMed

    Sheth, Sameer A; Abuelem, Tarek; Gale, John T; Eskandar, Emad N

    2011-03-30

    The basal ganglia (BG) appear to play a prominent role in associative learning, the process of pairing external stimuli with rewarding responses. Accumulating evidence suggests that the contributions of various BG components may be described within a reinforcement learning model, in which a broad repertoire of possible responses to environmental stimuli are evaluated before the most profitable one is chosen. The striatum receives diverse cortical inputs, providing a rich source of contextual information about environmental cues. It also receives projections from midbrain dopaminergic neurons, whose phasic activity reflects a reward prediction error signal. These coincident information streams are well suited for evaluating responses and biasing future actions toward the most profitable response. Still lacking in this model is a mechanistic description of how initial response variability is generated. To investigate this question, we recorded the activity of single neurons in the globus pallidus internus (GPi), the primary BG output nucleus, in nonhuman primates (Macaca mulatta) performing a motor associative learning task. A subset (29%) of GPi neurons showed learning-related effects, decreasing firing during the early stages of learning, then returning to higher baseline rates as associations were mastered. On a trial-by-trial basis, lower firing rates predicted exploratory behavior, whereas higher rates predicted an exploitive response. These results suggest that, during associative learning, BG output is initially permissive, allowing exploration of a variety of responses. Once a profitable response is identified, increased GPi activity suppresses alternative responses, sharpening the response profile and encouraging exploitation of the profitable learned behavior. PMID:21451026

  17. Humanized Foxp2 specifically affects cortico-basal ganglia circuits.

    PubMed

    Reimers-Kipping, S; Hevers, W; Pääbo, S; Enard, W

    2011-02-23

    It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution and influence aspects of speech and language. Recently it was shown that when these substitutions are introduced into the endogenous Foxp2 gene of mice, they increase dendrite length and long-term depression (LTD) in medium spiny neurons of the striatum. Here we investigated if these effects are found in other brain regions. We found that neurons in the cerebral cortex, the thalamus and the striatum have increased dendrite lengths in the humanized mice whereas neurons in the amygdala and the cerebellum do not. In agreement with previous work we found increased LTD in medium spiny neurons, but did not detect alterations of synaptic plasticity in Purkinje cells. We conclude that although Foxp2 is expressed in many brain regions and has multiple roles during mammalian development, the evolutionary changes that occurred in the protein in human ancestors specifically affect brain regions that are connected via cortico-basal ganglia circuits. PMID:21111790

  18. Basal ganglia outputs map instantaneous position coordinates during behavior.

    PubMed

    Barter, Joseph W; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A; Bartholomew, Ryan A; Yin, Henry H

    2015-02-11

    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions. PMID:25673860

  19. Saccade learning with concurrent cortical and subcortical basal ganglia loops

    PubMed Central

    N'Guyen, Steve; Thurat, Charles; Girard, Benoît

    2014-01-01

    The Basal Ganglia (BG) is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks. We propose a model of saccade generation with reinforcement learning capabilities based on our previous BG and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of the saccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks. The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not). Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate. PMID:24795615

  20. Observation of sonified movements engages a basal ganglia frontocortical network

    PubMed Central

    2013-01-01

    Background Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements. Results Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli. Conclusions We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation. PMID:23496827

  1. Interconnections of identified multiaction interneurons in buccal ganglia of Aplysia.

    PubMed

    Gardner, D

    1977-03-01

    1. The 26 identified neurons of Aplysia buccal ganglia include 4 interneurons and their follower cells. Each interneuron makes cholinergic synaptic connections on eight identified ipsilateral follower neurons. Each interneuronal action potential also produces a zero-latency, Mg-intensitive electrotonic coupling potential in one cholinergic and electrotonic input from the interneurons. Electrotonic connections are bidirectional and nonrectifying. 2. Ipsilateral pairs of interneurons receive extensive common synaptic input from several unidentified neurons: each interneuron also receives some input not received by the other. These pairs are linked by bidirectional nonrectifying electronic coupling which is insensitive to high Mg. As a consequence of this organization, ipsilateral interneuron pairs can fire a) independently, or b) synchronously, or c) one active interneuron can depolarize the other. 3. Each follower receiving synaptic input from one ipsilateral interneuron also receives similar input from the other interneuron. Common follower cells thus receive a) asynchronous PSPs, or b) large summated PSPs, or c) an increased number of PSPs from each interneuron. The latter two modes constitute feed-forward summation of interneuronal action. 4. Interneuronal output is confined to ipsilateral neurons. Symmetric pairs of interneurons are coordinated by common inputs and are not directly interconnected by either chemical or electrotonic synapses. Synchrony of firing of symmetric pairs is, therefore, looser than that of ipsilateral pairs. PMID:845626

  2. Origins of basal ganglia output signals in singing juvenile birds

    PubMed Central

    Pidoux, Morgane; Bollu, Tejapratap; Riccelli, Tori

    2014-01-01

    Across species, complex circuits inside the basal ganglia (BG) converge on pallidal output neurons that exhibit movement-locked firing patterns. Yet the origins of these firing patterns remain poorly understood. In songbirds during vocal babbling, BG output neurons homologous to those found in the primate internal pallidal segment are uniformly activated in the tens of milliseconds prior to syllable onsets. To test the origins of this remarkably homogenous BG output signal, we recorded from diverse upstream BG cell types during babbling. Prior to syllable onsets, at the same time that internal pallidal segment-like neurons were activated, putative medium spiny neurons, fast spiking and tonically active interneurons also exhibited transient rate increases. In contrast, pallidal neurons homologous to those found in primate external pallidal segment exhibited transient rate decreases. To test origins of these signals, we performed recordings following lesion of corticostriatal inputs from premotor nucleus HVC. HVC lesions largely abolished these syllable-locked signals. Altogether, these findings indicate a striking homogeneity of syllable timing signals in the songbird BG during babbling and are consistent with a role for the indirect and hyperdirect pathways in transforming cortical inputs into BG outputs during an exploratory behavior. PMID:25392171

  3. Basal Ganglia Contributions to Motor Control: A Vigorous Tutor

    PubMed Central

    Turner, Robert S.; Desmurget, Michel

    2010-01-01

    SUMMARY OF RECENT ADVANCES The roles of the basal ganglia (BG) in motor control are much debated. Many influential hypotheses have grown from studies in which output signals of the BG were not blocked, but pathologically-disturbed. A weakness of that approach is that the resulting behavioral impairments reflect degraded function of the BG per se mixed together with secondary dysfunctions of BG-recipient brain areas. To overcome that limitation, several studies have focused on the main skeletomotor output region of the BG, the globus pallidus internus (GPi). Using single-cell recording and inactivation protocols these studies provide consistent support for two hypotheses: the BG modulates movement performance (“vigor”) according to motivational factors (i.e., context-specific cost/reward functions) and the BG contributes to motor learning. Results from these studies also add to the problems that confront theories positing that the BG selects movement, inhibits unwanted motor responses, corrects errors online, or stores and produces well-learned motor skills. PMID:20850966

  4. Athymhormia and disorders of motivation in Basal Ganglia disease.

    PubMed

    Habib, Michel

    2004-01-01

    The author proposes a general model of human motivation as a separate function at the interface between emotion and action, which can be ascribed to subcortical circuits that are mainly centered on a subset of the basal ganglia and on their limbic connections. It is argued that the long-standing historical understatement of the notion of motivation in neurology is not only due to the complexity of the issue, which has proven hard to disentangle from other domains of dysfunction, but also to the persistence of some misleading conceptual orientations in the way neurologists have considered the brain mechanisms of goal-directed action, torn between a nonspecific "activation" view and an exclusively cognitive conception of motivation. How combining early clinical intuitions of some psychiatrists, careful clinical observations of neurological patients, and data derived from experimental studies in animals provide the basis for a coherent model of human motivation and its specific impairment in clinical neurology is explained. Clinical implications that can be drawn from such a model for some neuropsychiatric conditions are proposed. PMID:15616180

  5. Native opioid-like peptides in Squilla mantis ganglia.

    PubMed

    Marino, G; Palmisano, A; Di Marzo, V; Melck, D; Miralto, A

    1985-01-01

    To detect the presence of a mammalian-like enkephalin precursor in suboesophageal ganglia of Squilla mantis, an arthropod shown to be sensitive in vivo to opiates [8], protein acid extracts were fractionated by gel filtration into three large pools: A(Mr greater than 65,000), B(10,000 less than Mr less than 65,000) and C(Mr less than 10,000). Only the low molecular weight pool, pool C, showed opioid-like activity when assayed by displacing labeled D-Ala2-D-Leu5-enkephalin from rat brain membranes. After trypsin and carboxypeptidase B proteolysis, pool A remained inactive, while pool B turned out to be active and was shown to inhibit the twitch response of electrically stimulated guinea-pig ileum. After HPLC fractionation of proteolyzed pool B, most of the opioid-like activity was found to be associated with a fraction showing an elution volume different from that of opioid peptide standards. Furthermore, no fraction showed immunoreactivity with anti-Met-enkephalin antibodies. The results suggest that native opioid-like peptides are present in Squilla mantis and are most likely released from higher molecular weight precursor(s). PMID:3831968

  6. Cytokine Effects on the Basal Ganglia and Dopamine Function: the Subcortical Source of Inflammatory Malaise

    PubMed Central

    Felger, Jennifer C.; Miller, Andrew H.

    2012-01-01

    Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. PMID:23000204

  7. Basal Ganglia Subcircuits Distinctively Encode the Parsing and Concatenation of Action Sequences

    PubMed Central

    Jin, Xin; Tecuapetla, Fatuel; Costa, Rui M

    2014-01-01

    Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral sequence at the neural level. Using a task where mice learn rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. Besides start/stop activity signaling sequence parsing, we found neurons displaying inhibited or sustained activity throughout the execution of an entire sequence. This sustained activity covaried with the rate of execution of individual sequence elements, consistent with motor concatenation. Direct and indirect pathways of basal ganglia were concomitantly active during sequence initiation, but behaved differently during sequence performance, revealing a more complex functional organization of these circuits than previously postulated. These results have important implications for understanding the functional organization of basal ganglia during the learning and execution of action sequences. PMID:24464039

  8. A spiking neural network based on the basal ganglia functional anatomy.

    PubMed

    Baladron, Javier; Hamker, Fred H

    2015-07-01

    We introduce a spiking neural network of the basal ganglia capable of learning stimulus-action associations. We model learning in the three major basal ganglia pathways, direct, indirect and hyperdirect, by spike time dependent learning and considering the amount of dopamine available (reward). Moreover, we allow to learn a cortico-thalamic pathway that bypasses the basal ganglia. As a result the system develops new functionalities for the different basal ganglia pathways: The direct pathway selects actions by disinhibiting the thalamus, the hyperdirect one suppresses alternatives and the indirect pathway learns to inhibit common mistakes. Numerical experiments show that the system is capable of learning sets of either deterministic or stochastic rules. PMID:25863288

  9. Symmetric Basal Ganglia Lesion in a Diabetic Dialysis Patient: Recurrence and Pathogenesis

    PubMed Central

    2015-01-01

    This paper describes a diabetic dialysis patient presenting two episodes of symmetric basal ganglia lesions occurring 18 months apart, and discusses the MR imaging findings and the pathogenesis of this condition. PMID:25924173

  10. The evolutionary origin of the vertebrate basal ganglia and its role in action selection

    PubMed Central

    Grillner, Sten; Robertson, Brita; Stephenson-Jones, Marcus

    2013-01-01

    The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters. We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding. A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended. Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the ‘indirect loop’ in mammals as well as lamprey. We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour. PMID:23318875

  11. Mechanism of parkinsonian neuronal oscillations in the primate basal ganglia: some considerations based on our recent work

    PubMed Central

    Nambu, Atsushi; Tachibana, Yoshihisa

    2014-01-01

    Accumulating evidence suggests that abnormal neuronal oscillations in the basal ganglia (BG) contribute to the manifestation of parkinsonian symptoms. In this article, we would like to summarize our recent work on the mechanism underlying abnormal oscillations in the parkinsonian state and discuss its significance in pathophysiology of Parkinson’s disease. We recorded neuronal activity in the BG of parkinsonian monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Systemic administration of L-DOPA alleviated parkinsonian motor signs and decreased abnormal neuronal oscillations (8–15 Hz) in the internal (GPi) and external (GPe) segments of the globus pallidus and the subthalamic nucleus (STN). Inactivation of the STN by muscimol (GABAA receptor agonist) injection also ameliorated parkinsonian signs and suppressed GPi oscillations. The blockade of glutamatergic inputs to the STN by local microinjection of a mixture of 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (glutamatergic NMDA receptor antagonist) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (glutamatergic AMPA/kainate receptor antagonist) suppressed neuronal oscillations in the STN. STN oscillations were also attenuated by the blockade of GABAergic neurotransmission from the GPe to the STN by muscimol inactivation of the GPe. These results suggest that cortical glutamatergic inputs to the STN and reciprocal GPe-STN interconnections are both important for the generation and amplification of the oscillatory activity of GPe and STN neurons in the parkinsonian state. The oscillatory activity in the STN is subsequently transmitted to the GPi and may contribute to manifestation of parkinsonian symptoms. PMID:24904309

  12. Minicolumnar abnormalities in autism.

    PubMed

    Casanova, Manuel F; van Kooten, Imke A J; Switala, Andrew E; van Engeland, Herman; Heinsen, Helmut; Steinbusch, Harry W M; Hof, Patrick R; Trippe, Juan; Stone, Janet; Schmitz, Christoph

    2006-09-01

    Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V (CW)), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 microm in controls and 25.7 microm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity. PMID:16819561

  13. A Rare Stapes Abnormality

    PubMed Central

    Kanona, Hala; Virk, Jagdeep Singh; Kumar, Gaurav; Chawda, Sanjiv; Khalil, Sherif

    2015-01-01

    The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively. PMID:25628909

  14. MRI-identified abnormalities and wrist range of motion in asymptomatic versus symptomatic computer users

    PubMed Central

    2010-01-01

    Background Previous work has shown an association between restricted wrist range of motion (ROM) and upper extremity musculoskeletal disorders in computer users. We compared the prevalence of MRI-identified wrist abnormalities and wrist ROM between asymptomatic and symptomatic computer users. Methods MR images at 1.5 T of both wrists were obtained from 10 asymptomatic controls (8 F, 2 M) and 14 computer users (10 F, 4 M) with chronic wrist pain (10 bilateral; 4 right-side). Maximum wrist range of motion in flexion and radioulnar deviation was measured with an electrogoniometer. Results Extraosseous ganglia were identified in 66.6% of asymptomatic wrists and in 75% of symptomatic wrists. Intraosseous ganglia were identified in 45.8% of asymptomatic wrists and in 75% of symptomatic wrists, and were significantly (p < .05) larger in the symptomatic wrists. Distal ECU tendon instability was identified in 58.4% of both asymptomatic and symptomatic wrists. Dominant wrist flexion was significantly greater in the asymptomatic group (68.8 ± 6.7 deg.) compared to the symptomatic group (60.7 ± 7.3 deg.), p < .01. There was no significant correlation between wrist flexion and intraosseous ganglion burden (p = .09) Conclusions This appears to be the first MRI study of wrist abnormalities in computer users. This study demonstrates that a variety of wrist abnormalities are common in computer users and that only intraosseous ganglia prevalence and size differed between asymptomatic and symptomatic wrists. Flexion was restricted in the dominant wrist of the symptomatic group, but the correlation between wrist flexion and intraosseous ganglion burden did not reach significance. Flexion restriction may be an indicator of increased joint loading, and identifying the cause may help to guide preventive and therapeutic interventions. PMID:21108817

  15. Cognitive deficits in animal models of basal ganglia disorders.

    PubMed

    Brooks, Simon P; Dunnett, Stephen B

    2013-03-01

    The two most common neurological disorders of the basal ganglia are Parkinson's disease (PD) and Huntington's disease (HD). The most overt symptoms of these diseases are motoric, reflecting the loss of the striatal medium spiny neurons in HD and ascending substantia nigra dopaminergic cells in PD. However, both disease processes induce insidious psychiatric and cognitive syndromes that can manifest well in advance of the onset of motor deficits. These early deficits provide an opportunity for prophylactic therapeutic intervention in order to retard disease progression from the earliest possible point. In order to exploit this opportunity, animal models of HD and PD are being probed for the specific cognitive deficits represented in the disease states. At the neuronal level, these deficits are typically, but not exclusively, mediated by disruption of parallel corticostriatal loops that integrate motor information with sensory and higher order, "executive" cognitive functions. Dysfunction in these systems can be probed with sensitive behavioural tests that selectively probe these cognitive functions in mouse models with focal lesions of striatal or cortical regions, or of specific neurotransmitter systems. Typically these tests were designed and validated in rats. With the advent of genetically modified mouse models of disease, validated tests provide an opportunity to screen mouse models of disease for early onset cognitive deficits. This review seeks to draw together the literature on cognitive deficits in HD and PD, to determine the extent to which these deficits are represented in the current animal models of disease, and to evaluate the viability of selecting cognitive deficits as potential therapeutic targets. This article is part of a Special Issue entitled 'Animal Models'. PMID:22588013

  16. Intraneuronal angiotensinergic system in rat and human dorsal root ganglia.

    PubMed

    Patil, Jaspal; Schwab, Alexander; Nussberger, Juerg; Schaffner, Thomas; Saavedra, Juan M; Imboden, Hans

    2010-06-01

    To elucidate the local formation of angiotensin II (Ang II) in the neurons of sensory dorsal root ganglia (DRG), we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of protein renin, Ang II, Substance P and calcitonin gene-related peptide (CGRP) in the rat and human thoracic DRG. Quantitative real time PCR (qRT-PCR) studies revealed that rat DRG expressed substantial amounts of Ang-N- and ACE mRNA, while renin mRNA as well as the protein renin were untraceable. Cathepsin D-mRNA and cathepsin D-protein were detected in the rat DRG indicating the possibility of existence of pathways alternative to renin for Ang I formation. Angiotensin peptides were successfully detected with high performance liquid chromatography and radioimmunoassay in human DRG extracts. In situ hybridization in rat DRG confirmed additionally expression of Ang-N mRNA in the cytoplasm of numerous neurons. Intracellular Ang II staining could be shown in number of neurons and their processes in both the rat and human DRG. Interestingly we observed neuronal processes with angiotensinergic synapses en passant, colocalized with synaptophysin, within the DRG. In the DRG, we also identified by qRT-PCR, expression of Ang II receptor AT(1A) and AT(2)-mRNA while AT(1B)-mRNA was not traceable. In some neurons Substance P and CGRP were found colocalized with Ang II. The intracellular localization and colocalization of Ang II with Substance P and CGRP in the DRG neurons may indicate a participation and function of Ang II in the regulation of nociception. In conclusion, these results suggest that Ang II may be produced locally in the neurons of rat and human DRG and act as a neurotransmitter. PMID:20346377

  17. Varicella-zoster virus latency in human ganglia.

    PubMed

    Kennedy, Peter G E

    2002-01-01

    Varicella-zoster virus (VZV) is a human herpesvirus which causes varicella (chickenpox) as a primary infection, and, following a variable period during which it remains in latent form in trigeminal and dorsal root ganglia, reactivates in later life to cause herpes zoster (shingles). VZV is a significant cause of neurological disease including post-herpetic neuralgia which may be persistent and highly resistant to treatment, and small and large vessel encephalitis. VZV infections are more frequent with advancing age and in immunocompromised individuals. An understanding of the mechanisms of latency is crucial in developing effective therapies for VZV infections of the nervous system. Such studies have been hampered by the difficulties in working with the virus and also the lack of a good animal model of VZV latency. It is known that the ganglionic VZV burden during latency is low. Two of the key questions that have been addressed are the cellular site of latent VZV and the identity of the viral genes which are transcribed during latency. There is now a consensus that latent VZV resides predominantly in ganglionic neurons with less frequent infection of non-neuronal satellite cells. There is considerable evidence to show that at least five viral genes are transcribed during latency. Unlike herpes simplex virus-1 latency, viral protein expression has been demonstrated during VZV latency. A precise knowledge of which viral genes are expressed is crucial in devising novel antiviral therapy using expressed genes as therapeutic targets. Whether gene expression at both the transcriptional and translational levels is more extensive than currently reported will require much more work and probably new molecular technology. PMID:12211045

  18. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia

    PubMed Central

    LI, QINWEN; CHEN, JIANGHAI; CHEN, YANHUA; CONG, XIAOBIN; CHEN, ZHENBING

    2016-01-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post-compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR-labeled DRG neurons were significantly higher, relative to the sham-operated group, however, the numbers of FG-labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)-extracellular signal-regulated kinase 1/2, and significantly lower levels of p-c-Jun N-terminal kinase and p-p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF-β1, CTGF and collagen type I, with involvement of the mitogen-activated protein kinase signaling pathway. PMID:26820076

  19. A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease.

    PubMed

    Kumaravelu, Karthik; Brocker, David T; Grill, Warren M

    2016-04-01

    Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG. PMID:26867734

  20. Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette's disorder.

    PubMed

    Cheon, Keun-Ah; Ryu, Young-Hoon; Namkoong, Kee; Kim, Chan-Hyung; Kim, Jae-Jin; Lee, Jong Doo

    2004-01-15

    There is evidence that abnormalities in the dopaminergic system involving the dopamine transporter (DAT) are involved in the pathophysiology of Tourette's disorder (TD) from previous studies using [(123)I]2beta-carbomethoxy-3-(4-iodophenyl)tropane ([(123)I]beta-CIT) and single photon emission tomography (SPECT). However, because those studies were performed in medicated adult patients with TD, we decided to compare DAT densities in nine drug-naive children with TD and eight normal children. The children with TD did not suffer from associated psychiatric problems such as obsessive-compulsive symptoms, attention deficit hyperactivity disorder, anxiety, depression and developmental difficulties. We performed brain SPECT 2 h after the intravenous administration of I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane ([(123)I]IPT) and carried out both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity of tics in children with TD assessed with the Yale Global Tic Severity Scale (YGTSS) and the specific/non-specific DAT binding ratio of the basal ganglia. Drug-naive children with TD showed a significantly increased specific/non-specific DAT binding ratio in the basal ganglia compared with normal children that did not correlate significantly with the severity of tics. Our results with drug-naive children with TD between the ages of 6 and 12 may help to clarify previous findings concerning DAT binding in adult patients with TD and suggest that DAT densities may be associated directly with the pathophysiology of TD, regardless of disease progress or drug effect. PMID:14972371

  1. Parsing abnormal grain growth in specialty aluminas

    NASA Astrophysics Data System (ADS)

    Lawrence, Abigail Kremer

    Grain growth in alumina is strongly affected by the impurities present in the material. Certain impurity elements are known to have characteristic effects on abnormal grain growth in alumina. Specialty alumina powders contain multiple impurity species including MgO, CaO, SiO2, and Na 2O. In this work, sintered samples made from alumina powders containing various amounts of the impurities in question were characterized by their grain size and aspect ratio distributions. Multiple quantitative methods were used to characterize and classify samples with varying microstructures. The grain size distributions were used to partition the grain size population into subpopulations depending on the observed deviation from normal behavior. Using both grain size and aspect ratio a new visual representation for a microstructure was introduced called a morphology frequency map that gives a fingerprint for the material. The number of subpopulations within a sample and the shape of the distribution on the morphology map provided the basis for a classification scheme for different types of microstructures. Also using the two parameters a series of five metrics were calculated that describe the character of the abnormal grains in the sample, these were called abnormal character values. The abnormal character values describe the fraction of grains that are considered abnormal, the average magnitude of abnormality (including both grain size and aspect ratio), the average size, and variance in size. The final metric is the correlation between grain size and aspect ratio for the entire population of grains. The abnormal character values give a sense of how different from "normal" the sample is, given the assumption that a normal sample has a lognormal distribution of grain size and a Gaussian distribution of aspect ratios. In the second part of the work the quantified measures of abnormality were correlated with processing parameters such as composition and heat treatment conditions. A multivariate statistical tool called canonical correlation analysis was adopted to seek out relationships between a set of input variables and the abnormal character values. The input variables include the MgO, CaO, Na 2O, and SiO2 contents, the ratio of MgO:(CaO+SiO2), and the annealing time and temperature. The analysis was applied to 33 different samples and showed that the composition ratio and MgO content were the strongest processing variables. These variables are most closely related to the correlation between grain size and aspect ratio, the average magnitude of abnormality, and the variance in grain size. The physical implications of these relationships are explored for a number of samples with different abnormal grain growth behaviors. Several of the samples contained a beta"-alumina phase that is shown to have a dampening effect on abnormal grain growth. TEM investigation provides evidence that there is a grain boundary complexion with a different composition and structure than the second phase. A series of samples are compared after annealing for different times and are shown to have very different behaviors as a result of the second phase competing with complexions for control over the microstructure.

  2. Clinico-radiological Characteristics of Spontaneous Basal Ganglia Hemorrhage, According to Regional Classification

    PubMed Central

    Kim, Do Young; Choo, Yeon Soo; Jang, E Wook; Chung, Joonho; Joo, Jin Yang

    2014-01-01

    Objective The clinico-radiologic features of the spontaneous basal ganglia hemorrhage (BGH) may often differ one from another, according to its regional location. Therefore, we attempted to classify the BGH into regional subgroups, and to extrapolate the distinct characteristics of each group of BGH. Materials and Methods A total of 103 BGHs were analyzed by retrospective review of medical records. BGH was classified according to four subgroups; anterior BGH; posterior BGH; lateral BGH; massive BGH. Results The most common BGH was the posterior BGH (56, 54.4%), followed by the lateral BGH (26, 25.2%), the massive BGH (12, 11.7%), and the anterior BGH (9, 8.7%). The shape of hemorrhage tended to be round in anterior, irregular in posterior, and ovoid in lateral BGH. A layered density of hematoma on initial computed tomography showed correlation with hematoma expansion (p = 0.016), which was observed more often in the postero-lateral group of BGH than in the anterior BGH group. Relatively better recovery from the initial insult was observed in the lateral BGH group than in the other regional BGH groups. The proportion of poor outcome (modified Rankin scale 4, 5, 6) was 100% in the massive, 41.1% in the posterior, 34.6% in the lateral, and 0% in the anterior BGH group. Conclusion We observed that BGH can be grouped according to its regional location and each group may have distinct characteristics. Thus, a more sophisticated clinical strategy tailored to each group of BGHs can be implemented. PMID:25340023

  3. Automated segmentation of multifocal basal ganglia T2*-weighted MRI hypointensities

    PubMed Central

    Glatz, Andreas; Bastin, Mark E.; Kiker, Alexander J.; Deary, Ian J.; Wardlaw, Joanna M.; Valdés Hernández, Maria C.

    2015-01-01

    Multifocal basal ganglia T2*-weighted (T2*w) hypointensities, which are believed to arise mainly from vascular mineralization, were recently proposed as a novel MRI biomarker for small vessel disease and ageing. These T2*w hypointensities are typically segmented semi-automatically, which is time consuming, associated with a high intra-rater variability and low inter-rater agreement. To address these limitations, we developed a fully automated, unsupervised segmentation method for basal ganglia T2*w hypointensities. This method requires conventional, co-registered T2*w and T1-weighted (T1w) volumes, as well as region-of-interest (ROI) masks for the basal ganglia and adjacent internal capsule generated automatically from T1w MRI. The basal ganglia T2*w hypointensities were then segmented with thresholds derived with an adaptive outlier detection method from respective bivariate T2*w/T1w intensity distributions in each ROI. Artefacts were reduced by filtering connected components in the initial masks based on their standardised T2*w intensity variance. The segmentation method was validated using a custom-built phantom containing mineral deposit models, i.e. gel beads doped with 3 different contrast agents in 7 different concentrations, as well as with MRI data from 98 community-dwelling older subjects in their seventies with a wide range of basal ganglia T2*w hypointensities. The method produced basal ganglia T2*w hypointensity masks that were in substantial volumetric and spatial agreement with those generated by an experienced rater (Jaccard index = 0.62 ± 0.40). These promising results suggest that this method may have use in automatic segmentation of basal ganglia T2*w hypointensities in studies of small vessel disease and ageing. PMID:25451469

  4. Friedreich ataxia: metal dysmetabolism in dorsal root ganglia

    PubMed Central

    2013-01-01

    Background Friedreich ataxia (FA) causes distinctive lesions of dorsal root ganglia (DRG), including neuronal atrophy, satellite cell hyperplasia, and absorption of dying nerve cells into residual nodules. Two mechanisms may be involved: hypoplasia of DRG neurons from birth and superimposed iron (Fe)- and zinc (Zn)-mediated oxidative injury. This report presents a systematic analysis of DRG in 7 FA patients and 13 normal controls by X-ray fluorescence (XRF) of polyethylene glycol-embedded DRG; double-label confocal immunofluorescence microscopy of Zn- and Fe-related proteins; and immunohistochemistry of frataxin and the mitochondrial marker, ATP synthase F1 complex V ?-polypeptide (ATP5B). Results XRF revealed normal total Zn- and Fe-levels in the neural tissue of DRG in FA (mean ± standard deviation): Zn=5.46±2.29 ?g/ml, Fe=19.99±13.26 ?g/ml in FA; Zn=8.16±6.19 ?g/ml, Fe=23.85±12.23 ?g/ml in controls. Despite these unchanged total metal concentrations, Zn- and Fe-related proteins displayed major shifts in their cellular localization. The Zn transporter Zip14 that is normally expressed in DRG neurons and satellite cells became more prominent in hyperplastic satellite cells and residual nodules. Metallothionein 3 (MT3) stains confirmed reduction of neuronal size in FA, but MT3 expression remained low in hyperplastic satellite cells. In contrast, MT1/2 immunofluorescence was prominent in proliferating satellite cells. Neuronal ferritin immunofluorescence declined but remained strong in hyperplastic satellite cells and residual nodules. Satellite cells in FA showed a larger number of mitochondria expressing ATB5B. Frataxin immunohistochemistry in FA confirmed small neuronal sizes, irregular distribution of reaction product beneath the plasma membrane, and enhanced expression in hyperplastic satellite cells. Conclusions The pool of total cellular Zn in normal DRG equals 124.8 ?M, which is much higher than needed for the proper function of Zn ion-dependent proteins. It is likely that any disturbance of Zn buffering by Zip14 and MT3 causes mitochondrial damage and cell death. In contrast to Zn, sequestration of Fe in hyperplastic satellite cells may represent a protective mechanism. The changes in the cellular localization of Zn- and Fe-handling proteins suggest metal transfer from degenerating DRG neurons to activated satellite cells and connect neuronal metal dysmetabolism with the pathogenesis of the DRG lesion in FA. PMID:24252376

  5. A review of pathologies associated with high T1W signal intensity in the basal ganglia on Magnetic Resonance Imaging

    PubMed Central

    Zaitout, Zahia; Romanowski, Charles; Karunasaagarar, Kavitasagary; Connolly, Daniel; Batty, Ruth

    2014-01-01

    Summary With several functions and a fundamental influence over cognition and motor functions, the basal ganglia are the cohesive centre of the brain. There are several conditions which affect the basal ganglia and these have various clinical and radiological manifestations. Nevertheless, on magnetic resonance imaging there is a limited differential diagnosis for those conditions presenting with T1 weighted spin echo hyperintensity within the central nervous system in general and the basal ganglia in particular. The aim of our review is to explore some of these basal ganglia pathologies and provide image illustrations. PMID:24900164

  6. A method of nodose ganglia injection in Sprague-Dawley rat.

    PubMed

    Calik, Michael W; Radulovacki, Miodrag; Carley, David W

    2014-01-01

    Afferent signaling via the vagus nerve transmits important general visceral information to the central nervous system from many diverse receptors located in the organs of the abdomen and thorax. The vagus nerve communicates information from stimuli such as heart rate, blood pressure, bronchopulmonary irritation, and gastrointestinal distension to the nucleus of solitary tract of the medulla. The cell bodies of the vagus nerve are located in the nodose and petrosal ganglia, of which the majority are located in the former. The nodose ganglia contain a wealth of receptors for amino acids, monoamines, neuropeptides, and other neurochemicals that can modify afferent vagus nerve activity. Modifying vagal afferents through systemic peripheral drug treatments targeted at the receptors on nodose ganglia has the potential of treating diseases such as sleep apnea, gastroesophageal reflux disease, or chronic cough. The protocol here describes a method of injection neurochemicals directly into the nodose ganglion. Injecting neurochemicals directly into the nodose ganglia allows study of effects solely on cell bodies that modulate afferent nerve activity, and prevents the complication of involving the central nervous system as seen in systemic neurochemical treatment. Using readily available and inexpensive equipment, intranodose ganglia injections are easily done in anesthetized Sprague-Dawley rats. PMID:25490160

  7. Decreased uptake of GABA by dorsal ganglia in methylmercury-treated rats

    SciTech Connect

    Araki, K.; Wakabayashi, M.; Sakimura, K.; Kushiya, E.; Ozawa, H.; Kumamoto, T.; Takahashi, Y.

    1981-11-01

    The uptake of 14C-GABA and 14C-choline by cerebral cortex slices did not show any change in rats which showed neurological signs 7 days after the last 7 methylmercury injections (10 mg/kg/day). However, 14C-GABA uptake by dorsal ganglia greatly decreased, although 14C-choline uptake did not decrease in dorsal ganglia. 14C-GABA uptake by cerebellum also was somewhat decreased. The degree of inhibition of 14C-GABA uptake by dorsal ganglia increased each day after the commencement of methylmercury injection. The decrease of 3H-GABA uptake by dorsal ganglia of methylmercury-injected rats was confirmed by autoradiography. Autoradiographic and inhibitor studies showed labelled GABA accumulated in the satellite glial cells. In vitro addition of methylmercury (10(-4)-10(-5) M) equally inhibited the uptake of GABA and choline by brain and dorsal ganglia slices. These studies may reveal a possible mechanism of methylmercury neuropathy.

  8. Selection of cortical dynamics for motor behaviour by the basal ganglia.

    PubMed

    Mannella, Francesco; Baldassarre, Gianluca

    2015-12-01

    The basal ganglia and cortex are strongly implicated in the control of motor preparation and execution. Re-entrant loops between these two brain areas are thought to determine the selection of motor repertoires for instrumental action. The nature of neural encoding and processing in the motor cortex as well as the way in which selection by the basal ganglia acts on them is currently debated. The classic view of the motor cortex implementing a direct mapping of information from perception to muscular responses is challenged by proposals viewing it as a set of dynamical systems controlling muscles. Consequently, the common idea that a competition between relatively segregated cortico-striato-nigro-thalamo-cortical channels selects patterns of activity in the motor cortex is no more sufficient to explain how action selection works. Here, we contribute to develop the dynamical view of the basal ganglia-cortical system by proposing a computational model in which a thalamo-cortical dynamical neural reservoir is modulated by disinhibitory selection of the basal ganglia guided by top-down information, so that it responds with different dynamics to the same bottom-up input. The model shows how different motor trajectories can so be produced by controlling the same set of joint actuators. Furthermore, the model shows how the basal ganglia might modulate cortical dynamics by preserving coarse-grained spatiotemporal information throughout cortico-cortical pathways. PMID:26537483

  9. A direct GABAergic output from the basal ganglia to frontal cortex.

    PubMed

    Saunders, Arpiar; Oldenburg, Ian A; Berezovskii, Vladimir K; Johnson, Caroline A; Kingery, Nathan D; Elliott, Hunter L; Xie, Tiao; Gerfen, Charles R; Sabatini, Bernardo L

    2015-05-01

    The basal ganglia are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning. Current models postulate that the basal ganglia modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs, respectively). The basal ganglia thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the basal ganglia, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT(+) cells, which have been historically identified as an extension of the nucleus basalis, as well as ChAT(-) cells, release the inhibitory neurotransmitter GABA (?-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus, GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signalling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the basal ganglia to modulate frontal cortices. PMID:25739505

  10. Position of Larval Tapeworms, Polypocephalus sp., in the Ganglia of Shrimp, Litopenaeus setiferus

    PubMed Central

    Carreon, Nadia; Faulkes, Zen

    2014-01-01

    Parasites that invade the nervous system of their hosts have perhaps the best potential to manipulate their host’s behavior, but how they manipulate the host, if they do at all, could depend on their position within the host’s nervous system. We hypothesize that parasites that live in the nervous system of their host will be randomly distributed if they exert their influence through non-specific effects (i.e., general pathology), but that their position in the nervous system will be non-random if they exert their influence by targeting specific neural circuits. We recorded the position of larval tapeworms, Polypocephalus sp., in the abdominal ganglia of white shrimp, Litopenaeus setiferus. Tapeworms are more common within ganglia than in the section of the nerve cord between ganglia, even though the nerve cord has a greater volume than the ganglia. The tapeworms are also more abundant in the periphery of the ganglia. Because most synaptic connections are within the central region of the ganglion, such positioning may represent a trade-off between controlling the nervous system and damaging it. PMID:24820854

  11. A Method of Nodose Ganglia Injection in Sprague-Dawley Rat

    PubMed Central

    Calik, Michael W.; Radulovacki, Miodrag; Carley, David W.

    2015-01-01

    Afferent signaling via the vagus nerve transmits important general visceral information to the central nervous system from many diverse receptors located in the organs of the abdomen and thorax. The vagus nerve communicates information from stimuli such as heart rate, blood pressure, bronchopulmonary irritation, and gastrointestinal distension to the nucleus of solitary tract of the medulla. The cell bodies of the vagus nerve are located in the nodose and petrosal ganglia, of which the majority are located in the former. The nodose ganglia contain a wealth of receptors for amino acids, monoamines, neuropeptides, and other neurochemicals that can modify afferent vagus nerve activity. Modifying vagal afferents through systemic peripheral drug treatments targeted at the receptors on nodose ganglia has the potential of treating diseases such as sleep apnea, gastroesophageal reflux disease, or chronic cough. The protocol here describes a method of injection neurochemicals directly into the nodose ganglion. Injecting neurochemicals directly into the nodose ganglia allows study of effects solely on cell bodies that modulate afferent nerve activity, and prevents the complication of involving the central nervous system as seen in systemic neurochemical treatment. Using readily available and inexpensive equipment, intranodose ganglia injections are easily done in anesthetized Sprague-Dawley rats. PMID:25490160

  12. Identifying the Basal Ganglia Network Model Markers for Medication-Induced Impulsivity in Parkinson's Disease Patients

    PubMed Central

    Balasubramani, Pragathi Priyadharsini; Chakravarthy, V. Srinivasa; Ali, Manal; Ravindran, Balaraman; Moustafa, Ahmed A.

    2015-01-01

    Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its impairment in PD. The results presented here not only show that computational modelling can be used as a valuable tool for understanding and interpreting clinical data, but they also show that computational modeling has the potential to become an invaluable tool to predict the onset of behavioral changes during disease progression. PMID:26042675

  13. P2X₇ receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia.

    PubMed

    Liu, Shuangmei; Shi, Qingming; Zhu, Qicheng; Zou, Ting; Li, Guilin; Huang, An; Wu, Bing; Peng, Lichao; Song, Miaomiao; Wu, Qin; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Lv, Qiulan; Zou, Lifang; Zhang, Xi; Ying, Mofeng; Li, Guodong; Liang, Shangdong

    2015-06-01

    Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint "Dachangshu" and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor. PMID:25527178

  14. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  15. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  16. Modiolus-hugging intracochlear electrode array with shape memory alloy.

    PubMed

    Min, Kyou Sik; Jun, Sang Beom; Lim, Yoon Seob; Park, Se-Ik; Kim, Sung June

    2013-01-01

    In the cochlear implant system, the distance between spiral ganglia and the electrodes within the volume of the scala tympani cavity significantly affects the efficiency of the electrical stimulation in terms of the threshold current level and spatial selectivity. Because the spiral ganglia are situated inside the modiolus, the central axis of the cochlea, it is desirable that the electrode array hugs the modiolus to minimize the distance between the electrodes and the ganglia. In the present study, we propose a shape-memory-alloy-(SMA-) embedded intracochlear electrode which gives a straight electrode a curved modiolus-hugging shape using the restoration force of the SMA as triggered by resistive heating after insertion into the cochlea. An eight-channel ball-type electrode array is fabricated with an embedded titanium-nickel SMA backbone wire. It is demonstrated that the electrode array changes its shape in a transparent plastic human cochlear model. To verify the safe insertion of the electrode array into the human cochlea, the contact pressures during insertion at the electrode tip and the contact pressures over the electrode length after insertion were calculated using a 3D finite element analysis. The results indicate that the SMA-embedded electrode is functionally and mechanically feasible for clinical applications. PMID:23762181

  17. Modiolus-Hugging Intracochlear Electrode Array with Shape Memory Alloy

    PubMed Central

    Min, Kyou Sik; Lim, Yoon Seob; Park, Se-Ik; Kim, Sung June

    2013-01-01

    In the cochlear implant system, the distance between spiral ganglia and the electrodes within the volume of the scala tympani cavity significantly affects the efficiency of the electrical stimulation in terms of the threshold current level and spatial selectivity. Because the spiral ganglia are situated inside the modiolus, the central axis of the cochlea, it is desirable that the electrode array hugs the modiolus to minimize the distance between the electrodes and the ganglia. In the present study, we propose a shape-memory-alloy-(SMA-) embedded intracochlear electrode which gives a straight electrode a curved modiolus-hugging shape using the restoration force of the SMA as triggered by resistive heating after insertion into the cochlea. An eight-channel ball-type electrode array is fabricated with an embedded titanium-nickel SMA backbone wire. It is demonstrated that the electrode array changes its shape in a transparent plastic human cochlear model. To verify the safe insertion of the electrode array into the human cochlea, the contact pressures during insertion at the electrode tip and the contact pressures over the electrode length after insertion were calculated using a 3D finite element analysis. The results indicate that the SMA-embedded electrode is functionally and mechanically feasible for clinical applications. PMID:23762181

  18. Thalamic Contributions to Basal Ganglia-Related Behavioral Switching and Reinforcement

    PubMed Central

    Smith, Yoland; Surmeier, D. James; Redgrave, Peter; Kimura, Minoru

    2011-01-01

    Although the existence of prominent connections between the intralaminar thalamic nuclei and the basal ganglia have long been established, the limited knowledge of the functional relevance of this network has considerably hampered progress in our understanding of the neural mechanisms by which the thalamostriatal system integrates and regulates the basal ganglia circuitry. In this brief commentary, we will address this gap of knowledge through a discussion of the key points of a symposium entitled “Thalamic Contributions to Basal Ganglia-Related Behavioral Switching and Reinforcement” that will be presented at the 2011 Society for Neuroscience meeting. Recent anatomical and physiological data that support the role of the thalamostriatal system in action selection, attentional shifting and reinforcement will be discussed. We will also address the possibility that degeneration of the thalamostriatal system could underlie some of the deficits in redirection of attention in response to salient stimuli seen in Parkinson’s disease. PMID:22072662

  19. Influence of Acoustic Waves on Perchloroethylene Ganglia Dissolution in a Pore Network

    NASA Astrophysics Data System (ADS)

    Vogler, E. T.; Chrysikopoulos, C. V.

    2006-12-01

    A pore network consisting of a monolayer of 3-milimeter diameter glass beads was used to investigate the effects of acoustic waves on the dissolution of perchloroethylene (PCE) ganglia. Dissolution experiments were conducted with acoustic-wave frequencies ranging from 75 to 225 hertz (Hz) at a constant pressure amplitude of 3.68 kilopascals (kPa) applied to the inlet of the monolayer. Effluent dissolved PCE concentrations were observed to increase in the presence of acoustic waves. The greatest increase (over 300%) occurred at the lowest frequency employed (75 Hz). Ganglia mobilization experiments were also conducted, using a constant acoustic-wave frequency of 125 Hz and acoustic-pressure amplitude ranging from 0 to 39.07 kPa. Acoustic waves were observed to mobilize otherwise immobile PCE ganglia and break them apart. Results from this study suggest that the use of acoustic waves may be beneficial in ground-water contaminant remediation.

  20. MR-DTI and PET multimodal imaging of dopamine release within subdivisions of basal ganglia

    NASA Astrophysics Data System (ADS)

    Tziortzi, A.; Searle, G.; Tsoumpas, C.; Long, C.; Shotbolt, P.; Rabiner, E.; Jenkinson, M.; Gunn, R. N.

    2011-09-01

    The basal ganglia is a group of anatomical nuclei, functionally organised into limbic, associative and sensorimotor regions, which plays a central role in dopamine related neurological and psychiatric disorders. In this study, we combine two imaging modalities to enable the measurement of dopamine release in functionally related subdivisions of the basal ganglia. [11C]-(+)-PHNO Positron Emission Tomography (PET) measurements in the living human brain pre- and post-administration of amphetamine allow for the estimation of regional dopamine release. Combined Magnetic Resonance Diffusion Tensor Imaging (MR-DTI) data allows for the definition of functional territories of the basal ganglia from connectivity information. The results suggest that there is a difference in dopamine release among the connectivity derived functional subdivisions. Dopamine release is highest in the limbic area followed by the sensorimotor and then the associative area with this pattern reflected in both striatum and pallidum.

  1. Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease

    PubMed Central

    Redgrave, Peter; Rodriguez, Manuel; Smith, Yoland; Rodriguez-Oroz, Maria C.; Lehericy, Stephane; Bergman, Hagai; Agid, Yves; DeLong, Mahlon R.; Obeso, Jose A.

    2011-01-01

    Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson’s disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson’s disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. PMID:20944662

  2. Cross-Excitation in Peripheral Sensory Ganglia Associated with Pain Transmission.

    PubMed

    Omoto, Katsuhiro; Maruhama, Kotaro; Terayama, Ryuji; Yamamoto, Yumiko; Matsushita, Osamu; Sugimoto, Tomosada; Oguma, Keiji; Matsuka, Yoshizo

    2015-08-01

    Despite the absence of synaptic contacts, cross-excitation of neurons in sensory ganglia during signal transmission is considered to be chemically mediated and appears increased in chronic pain states. In this study, we modulated neurotransmitter release in sensory neurons by direct application of type A botulinum neurotoxin (BoNT/A) to sensory ganglia in an animal model of neuropathic pain and evaluated the effect of this treatment on nocifensive. Unilateral sciatic nerve entrapment (SNE) reduced the ipsilateral hindpaw withdrawal threshold to mechanical stimulation and reduced hindpaw withdrawal latency to thermal stimulation. Direct application of BoNT/A to the ipsilateral L4 dorsal root ganglion (DRG) was localized in the cell bodies of the DRG and reversed the SNE-induced decreases in withdrawal thresholds within 2 days of BoNT/A administration. Results from this study suggest that neurotransmitter release within sensory ganglia is involved in the regulation of pain-related signal transmission. PMID:26248078

  3. Cross-Excitation in Peripheral Sensory Ganglia Associated with Pain Transmission

    PubMed Central

    Omoto, Katsuhiro; Maruhama, Kotaro; Terayama, Ryuji; Yamamoto, Yumiko; Matsushita, Osamu; Sugimoto, Tomosada; Oguma, Keiji; Matsuka, Yoshizo

    2015-01-01

    Despite the absence of synaptic contacts, cross-excitation of neurons in sensory ganglia during signal transmission is considered to be chemically mediated and appears increased in chronic pain states. In this study, we modulated neurotransmitter release in sensory neurons by direct application of type A botulinum neurotoxin (BoNT/A) to sensory ganglia in an animal model of neuropathic pain and evaluated the effect of this treatment on nocifensive. Unilateral sciatic nerve entrapment (SNE) reduced the ipsilateral hindpaw withdrawal threshold to mechanical stimulation and reduced hindpaw withdrawal latency to thermal stimulation. Direct application of BoNT/A to the ipsilateral L4 dorsal root ganglion (DRG) was localized in the cell bodies of the DRG and reversed the SNE-induced decreases in withdrawal thresholds within 2 days of BoNT/A administration. Results from this study suggest that neurotransmitter release within sensory ganglia is involved in the regulation of pain-related signal transmission. PMID:26248078

  4. Distribution of HSV-1 and VZV in Ganglia of the Human Head and Neck

    PubMed Central

    Richter, Elizabeth R.; Dias, James K.; Gilbert, James E.; Atherton, Sally S.

    2009-01-01

    The distribution of the neurotropic alphaherpesviruses (HSV-1, HSV-2, and VZV) was determined in autonomic and sensory ganglia of the head and neck from formalin-fixed human cadavers. HSV-1 and VZV DNA were found in 18/58 and 16/58 trigeminal, 23/58 and 11/58 pterygopalatine, 25/60 and 14/60 ciliary, 25/48 and 11/48 geniculate, 15/50 and 8/50 otic, 14/47 and 4/47 submandibular, 18/58 and 10/58 superior cervical, and 12/36 and 1/36 nodose ganglia, respectively. HSV-2 was not detected in any site. Viral DNA positivity and location were independently distributed among autonomic and sensory ganglia of the human head and neck. PMID:19919304

  5. Hypofractionated Stereotactic Radiosurgery in a Large Bilateral Thalamic and Basal Ganglia Arteriovenous Malformation

    PubMed Central

    Nanda, Ashish; Litofsky, N. Scott

    2013-01-01

    Purpose. Arteriovenous malformations (AVMs) in the basal ganglia and thalamus have a more aggressive natural history with a higher morbidity and mortality than AVMs in other locations. Optimal treatment—complete obliteration without new neurological deficits—is often challenging. We present a patient with a large bilateral basal ganglia and thalamic AVM successfully treated with hypofractionated stereotactic radiosurgery (HFSRS) with intensity modulated radiotherapy (IMRT). Methods. The patient was treated with hypofractionated stereotactic radiosurgery to 30?Gy at margin in 5 fractions of 9 static fields with a minimultileaf collimator and intensity modulated radiotherapy. Results. At 10 months following treatment, digital subtraction angiography showed complete obliteration of the AVM. Conclusions. Large bilateral thalamic and basal ganglia AVMs can be successfully treated with complete obliteration by HFSRS with IMRT with relatively limited toxicity. Appropriate caution is recommended. PMID:24307961

  6. A Genome-Wide Screen to Identify Transcription Factors Expressed in Pelvic Ganglia of the Lower Urinary Tract

    PubMed Central

    Wiese, Carrie B.; Ireland, Sara; Fleming, Nicole L.; Yu, Jing; Valerius, M. Todd; Georgas, Kylie; Chiu, Han Sheng; Brennan, Jane; Armstrong, Jane; Little, Melissa H.; McMahon, Andrew P.; Southard-Smith, E. Michelle

    2012-01-01

    Relative positions of neurons within mature murine pelvic ganglia based on expression of neurotransmitters have been described. However the spatial organization of developing innervation in the murine urogenital tract (UGT) and the gene networks that regulate specification and maturation of neurons within the pelvic ganglia of the lower urinary tract (LUT) are unknown. We used whole-mount immunohistochemistry and histochemical stains to localize neural elements in 15.5 days post coitus (dpc) fetal mice. To identify potential regulatory factors expressed in pelvic ganglia, we surveyed expression patterns for known or probable transcription factors (TF) annotated in the mouse genome by screening a whole-mount in situ hybridization library of fetal UGTs. Of the 155 genes detected in pelvic ganglia, 88 encode TFs based on the presence of predicted DNA-binding domains. Neural crest (NC)-derived progenitors within the LUT were labeled by Sox10, a well-known regulator of NC development. Genes identified were categorized based on patterns of restricted expression in pelvic ganglia, pelvic ganglia and urethral epithelium, or pelvic ganglia and urethral mesenchyme. Gene expression patterns and the distribution of Sox10+, Phox2b+, Hu+, and PGP9.5+ cells within developing ganglia suggest previously unrecognized regional segregation of Sox10+ progenitors and differentiating neurons in early development of pelvic ganglia. Reverse transcription-PCR of pelvic ganglia RNA from fetal and post-natal stages demonstrated that multiple TFs maintain post-natal expression, although Pax3 is extinguished before weaning. Our analysis identifies multiple potential regulatory genes including TFs that may participate in segregation of discrete lineages within pelvic ganglia. The genes identified here are attractive candidate disease genes that may now be further investigated for their roles in malformation syndromes or in LUT dysfunction. PMID:22988430

  7. The subdiaphragmatic part of the phrenic nerve - morphometry and connections to autonomic ganglia.

    PubMed

    Loukas, Marios; Du Plessis, Maira; Louis, Robert G; Tubbs, R Shane; Wartmann, Christopher T; Apaydin, Nihal

    2016-01-01

    Few anatomical textbooks offer much information concerning the anatomy and distribution of the phrenic nerve inferior to the diaphragm. The aim of this study was to identify the subdiaphragmatic distribution of the phrenic nerve, the presence of phrenic ganglia, and possible connections to the celiac plexus. One hundred and thirty formalin-fixed adult cadavers were studied. The right phrenic nerve was found inferior to the diaphragm in 98% with 49.1% displaying a right phrenic ganglion. In 22.8% there was an additional smaller ganglion (right accessory phrenic ganglion). The remaining 50.9% had no grossly identifiable right phrenic ganglion. Most (65.5% of specimens) exhibited plexiform communications with the celiac ganglion, aorticorenal ganglion, and suprarenal gland. The left phrenic nerve inferior to the diaphragm was observed in 60% of specimens with 19% containing a left phrenic ganglion. No accessory left phrenic ganglia were observed. The left phrenic ganglion exhibited plexiform communications to several ganglia in 71.4% of specimens. Histologically, the right phrenic and left phrenic ganglia contained large soma concentrated in their peripheries. Both phrenic nerves and ganglia were closely related to the diaphragmatic crura. Surgically, sutures to approximate the crura for repair of hiatal hernias must be placed above the ganglia in order to avoid iatrogenic injuries to the autonomic supply to the diaphragm and abdomen. These findings could also provide a better understanding of the anatomy and distribution of the fibers of that autonomic supply. Clin. Anat. 29:120-128, 2016. © 2015 Wiley Periodicals, Inc. PMID:26457392

  8. The role of the basal ganglia in beat perception: neuroimaging and neuropsychological investigations.

    PubMed

    Grahn, Jessica A

    2009-07-01

    Perception of musical rhythms is culturally universal. Despite this special status, relatively little is known about the neurobiology of rhythm perception, particularly with respect to beat processing. Findings are presented here from a series of studies that have specifically examined the neural basis of beat perception, using functional magnetic resonance imaging (fMRI) and studying patients with Parkinson's disease. fMRI data indicate that novel beat-based sequences robustly activate the basal ganglia when compared to irregular, nonbeat sequences. Furthermore, although most healthy participants find it much easier to discriminate changes in beat-based sequences compared to irregular sequences, Parkinson's disease patients fail to show the same degree of benefit. Taken together, these data suggest that the basal ganglia are performing a crucial function in beat processing. The results of an additional fMRI study indicate that the role of the basal ganglia is strongly linked to internal generation of the beat. Basal ganglia activity is greater when participants listen to rhythms in which internal generation of the beat is required, as opposed to rhythms with strongly externally cued beats. Functional connectivity between part of the basal ganglia (the putamen) and cortical motor areas (premotor and supplementary motor areas) is also higher during perception of beat rhythms compared to nonbeat rhythms. Increased connectivity between cortical motor and auditory areas is found in those with musical training. The findings from these converging methods strongly implicate the basal ganglia in processing a regular beat, particularly when internal generation of the beat is required. PMID:19673753

  9. Evolution of the basal ganglia: dual-output pathways conserved throughout vertebrate phylogeny.

    PubMed

    Stephenson-Jones, Marcus; Ericsson, Jesper; Robertson, Brita; Grillner, Sten

    2012-09-01

    The basal ganglia, including the striatum, globus pallidus interna and externa (GPe), subthalamic nucleus (STN), and substantia nigra pars compacta, are conserved throughout vertebrate phylogeny and have been suggested to form a common vertebrate mechanism for action selection. In mammals, this circuitry is further elaborated by the presence of a dual-output nucleus, the substantia nigra pars reticulata (SNr), and the presence of modulatory input from the cholinergic pedunculopontine nucleus (PPN). We sought to determine whether these additional components of the mammalian basal ganglia are also present in one of the phylogenetically oldest vertebrates, the lamprey. We show, by using immunohistochemistry, tract tracing, and whole-cell recordings, that homologs of the SNr and PPN are present in the lamprey. Thus the SNr receives direct projections from inwardly rectifying γ-aminobutyric acid (GABA)-ergic striatal neurons expressing substance P, but it is also influenced by indirect basal ganglia projections from the STN and potentially the GPe. Moreover, GABAergic SNr projection neurons are tonically active and project to the thalamus and brainstem motor areas. The homolog of the PPN contains both cholinergic and GABAergic neurons and is connected with all the nuclei of the basal ganglia, supporting its proposed role as part of an extended basal ganglia. A separate group of cholinergic neurons dorsal to the PPN corresponds to the descending mesencephalic locomotor region. Our results suggest that dual-output nuclei are part of the ancestral basal ganglia and that the PPN appears to have coevolved as part of a mechanism for action selection common to all vertebrates. PMID:22351244

  10. Does varicella-zoster virus infection of the peripheral ganglia cause Chronic Fatigue Syndrome?

    PubMed

    Shapiro, Judith S

    2009-11-01

    This article posits that infection of the peripheral ganglia causes at least some cases of Chronic Fatigue Syndrome (CFS), with a neurotropic herpesvirus, particularly varicella-zoster virus (VZV), as the most likely cause of the infection. Virtually all CFS symptoms could be produced by an infection of the peripheral ganglia, with infection of the autonomic ganglia causing fatigue, postural hypotension, and sleep disturbances, and infection of the sensory ganglia causing sensory symptoms such as chronic pain. Furthermore, infections of the peripheral ganglia are known to cause long-term nerve dysfunction, which would help explain the chronic course of CFS. Herpesviruses have long been suspected as the cause of CFS; this theory has recently been supported by studies showing that administering antiherpes agents causes substantial improvement in some CFS patients. VZV is known to frequently reactivate in the peripheral ganglia of previously healthy adults and cause sudden, debilitating illness, making it a likely candidate as a cause of CFS. Moreover, many of the symptoms of CFS overlap with those of herpes zoster (shingles), with the exception that painful rash is not one of the symptoms of CFS. A model is therefore proposed in which CFS is one of the many manifestations of zoster sine herpete; that is, herpes zoster without rash. Furthermore, re-exposure to VZV in the form of chickenpox has become less common in the past few decades; without such re-exposure, immunity to VZV drops, which could explain the increased incidence of CFS. Co-infection with multiple herpesviruses is a possibility, as some CFS patients show signs of infection with other herpesviruses including Epstein-Barr, Cytomegalovirus, and HHV6. These three herpesviruses can attack immune cells, and may therefore promote neurotropic herpesvirus reactivation in the ganglia. The possibility of VZV as the causal agent in CFS has previously received almost no attention; the possibility that CFS involves infection of the peripheral ganglia has likewise been largely overlooked. This suggests that the search for a viral cause of CFS has been far from exhaustive. Several antiherpes drugs are available, as is a vaccine for VZV; more research into such agents as possible treatments for CFS is urgently needed. PMID:19520522

  11. Bilateral reversible basal ganglia changes associated with dystonia and hemifacial spasms in central nervous system lupus

    PubMed Central

    Christodoulou, Loucas; Siddiqui, Ata; D’Cruz, David; Andrews, Thomasin

    2015-01-01

    We report a 40-year-old woman with systemic lupus erythematosus (SLE) and associated inflammatory polyarthritis who presented with acute facial dystonic spasms. Her speech was also affected. An MRI brain showed bilateral symmetrical basal ganglia signal change on T2. This movement disorder was due to an acute manifestation of her lupus. Her symptoms resolved rapidly following treatment with (oral) steroids. Repeat MRI brain at 1 month showed complete resolution of the basal ganglia signal change. This is the first time that facial spasms and dystonia with corresponding MRI changes are reported as a presentation of lupus affecting the central nervous system (CNS lupus). PMID:26807375

  12. Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.

    PubMed

    Nicolas, Gaël; Pottier, Cyril; Charbonnier, Camille; Guyant-Maréchal, Lucie; Le Ber, Isabelle; Pariente, Jérémie; Labauge, Pierre; Ayrignac, Xavier; Defebvre, Luc; Maltête, David; Martinaud, Olivier; Lefaucheur, Romain; Guillin, Olivier; Wallon, David; Chaumette, Boris; Rondepierre, Philippe; Derache, Nathalie; Fromager, Guillaume; Schaeffer, Stéphane; Krystkowiak, Pierre; Verny, Christophe; Jurici, Snejana; Sauvée, Mathilde; Vérin, Marc; Lebouvier, Thibaud; Rouaud, Olivier; Thauvin-Robinet, Christel; Rousseau, Stéphane; Rovelet-Lecrux, Anne; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

    2013-11-01

    Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: <40, 40-60, and >60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression. PMID:24065723

  13. Classification of breast abnormalities using artificial neural network

    NASA Astrophysics Data System (ADS)

    Zaman, Nur Atiqah Kamarul; Rahman, Wan Eny Zarina Wan Abdul; Jumaat, Abdul Kadir; Yasiran, Siti Salmah

    2015-05-01

    Classification is the process of recognition, differentiation and categorizing objects into groups. Breast abnormalities are calcifications which are tumor markers that indicate the presence of cancer in the breast. The aims of this research are to classify the types of breast abnormalities using artificial neural network (ANN) classifier and to evaluate the accuracy performance using receiver operating characteristics (ROC) curve. The methods used in this research are ANN for breast abnormalities classifications and Canny edge detector as a feature extraction method. Previously the ANN classifier provides only the number of benign and malignant cases without providing information for specific cases. However in this research, the type of abnormality for each image can be obtained. The existing MIAS MiniMammographic database classified the mammogram images into three features only namely characteristic of background tissues, class of abnormality and radius of abnormality. However, in this research three other features are added-in. These three features are number of spots, area and shape of abnormalities. Lastly the performance of the ANN classifier is evaluated using ROC curve. It is found that ANN has an accuracy of 97.9% which is considered acceptable.

  14. Chromosomal abnormalities in human sperm

    SciTech Connect

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

  15. Haematological abnormalities in mitochondrial disorders

    PubMed Central

    Finsterer, Josef; Frank, Marlies

    2015-01-01

    INTRODUCTION This study aimed to assess the kind of haematological abnormalities that are present in patients with mitochondrial disorders (MIDs) and the frequency of their occurrence. METHODS The blood cell counts of a cohort of patients with syndromic and non-syndromic MIDs were retrospectively reviewed. MIDs were classified as ‘definite’, ‘probable’ or ‘possible’ according to clinical presentation, instrumental findings, immunohistological findings on muscle biopsy, biochemical abnormalities of the respiratory chain and/or the results of genetic studies. Patients who had medical conditions other than MID that account for the haematological abnormalities were excluded. RESULTS A total of 46 patients (‘definite’ = 5; ‘probable’ = 9; ‘possible’ = 32) had haematological abnormalities attributable to MIDs. The most frequent haematological abnormality in patients with MIDs was anaemia. 27 patients had anaemia as their sole haematological problem. Anaemia was associated with thrombopenia (n = 4), thrombocytosis (n = 2), leucopenia (n = 2), and eosinophilia (n = 1). Anaemia was hypochromic and normocytic in 27 patients, hypochromic and microcytic in six patients, hyperchromic and macrocytic in two patients, and normochromic and microcytic in one patient. Among the 46 patients with a mitochondrial haematological abnormality, 78.3% had anaemia, 13.0% had thrombopenia, 8.7% had leucopenia and 8.7% had eosinophilia, alone or in combination with other haematological abnormalities. CONCLUSION MID should be considered if a patient’s abnormal blood cell counts (particularly those associated with anaemia, thrombopenia, leucopenia or eosinophilia) cannot be explained by established causes. Abnormal blood cell counts may be the sole manifestation of MID or a collateral feature of a multisystem problem. PMID:26243978

  16. Abuse of amphetamines and structural abnormalities in the brain.

    PubMed

    Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

    2008-10-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure. PMID:18991959

  17. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure. PMID:18991959

  18. Conditional Routing of Information to the Cortex: A Model of the Basal Ganglia's Role in Cognitive Coordination

    ERIC Educational Resources Information Center

    Stocco, Andrea; Lebiere, Christian; Anderson, John R.

    2010-01-01

    The basal ganglia play a central role in cognition and are involved in such general functions as action selection and reinforcement learning. Here, we present a model exploring the hypothesis that the basal ganglia implement a conditional information-routing system. The system directs the transmission of cortical signals between pairs of regions…

  19. Conditional Routing of Information to the Cortex: A Model of the Basal Ganglia's Role in Cognitive Coordination

    ERIC Educational Resources Information Center

    Stocco, Andrea; Lebiere, Christian; Anderson, John R.

    2010-01-01

    The basal ganglia play a central role in cognition and are involved in such general functions as action selection and reinforcement learning. Here, we present a model exploring the hypothesis that the basal ganglia implement a conditional information-routing system. The system directs the transmission of cortical signals between pairs of regions…

  20. Intracerebroventricular administration of nerve growth factor induces gliogenesis in sensory ganglia, dorsal root, and within the dorsal root entry zone.

    PubMed

    Schlachetzki, Johannes C M; Pizzo, Donald P; Morrissette, Debbi A; Winkler, Jürgen

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100? revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root. PMID:24738070

  1. Echocardiographic abnormalities following cardiac radiation

    SciTech Connect

    Perrault, D.J.; Levy, M.; Herman, J.D.; Burns, R.J.; Bar Shlomo, B.Z.; Druck, M.N.; Wu, W.Q.; McLaughlin, P.R.; Gilbert, B.W.

    1985-04-01

    Five years or more after receiving cardiac radiation, 41 patients with Hodgkin's disease and seminoma in remission were subjected to echocardiography. The abnormalities detected included pericardial thickening in 70%, thickening of the aortic and/or mitral valves in 28%, right ventricular dilatation or hypokinesis in 39%, and left ventricular dysfunction in 39%. In the 23 patients treated by an upper mantle technique with shielding, the incidence of right ventricular abnormalities and valvular thickening was significantly lower than in patients treated with modified techniques. Although no symptoms were attributable to the observed abnormalities, longer follow-up time may reveal important functional implications.

  2. [Seizures revealing phosphocalcic metabolism abnormalities].

    PubMed

    Hmami, F; Chaouki, S; Benmiloud, S; Souilmi, F Z; Abourazzak, S; Idrissi, M; Atmani, S; Bouharrou, A; Hida, M

    2014-01-01

    Hypocalcemia due to hypoparathyroidism produces a broad spectrum of clinical manifestations, but overt symptoms may be sparse. One unusual presentation is onset or aggravation of epilepsy in adolescence revealing hypoparathyroidism. This situation can lead to delayed diagnosis, with inefficacity of the antiepileptic drugs. We report five cases of adolescence-onset epilepsy with unsuccessful antiepileptic therapy, even with gradually increasing dose. Physical examination revealed signs of hypocalcemia, confirmed biologically. Full testing disclosed the origin of the seizures: hypoparathyroidism in three patients and pseudohypoparathyroidism in the other two. In four of five patients, computed tomography showed calcification of the basal ganglia, defining Fahr's syndrome. The patients were treated with oral calcium and active vitamin D (1-alphahydroxy vitamin D3). Seizure frequency progressively decreased and serum calcium levels returned to normal. These cases illustrate the importance of the physical examination and of routine serum calcium assay in patients with new-onset epileptic seizures in order to detect hypocalcemia secondary to hypoparathyroidism. PMID:24726042

  3. Intramuscular nerve distribution in bladder and the relationship between intramuscular ganglia and bladder function in man and dog

    PubMed Central

    Zhao, Zeju; Xu, Qian; Lu, Li; Luo, Xu; Fu, Xiaoyun

    2014-01-01

    In clinical, the relationship between bladder intramuscular nerve and function is also elusive. This study aims to compare the bladder intramuscular nerve distribution and its characteristics and significance in human and dog. Eleven dogs’ bladders were stained by Sihler’s and HE techniques. Fifteen human bladders were adopted by Sihler’s staining, using 10% formaldehyde to fix 12 weeks, 7 by HE dyeing fixes 24 hours. Results indicated that man’s bladder was triangularpyramid-shaped. While dog’s bladder was spherical-shaped and its muscle fibers arrange were irregularly shaped. Longitudinal muscle of the outer layer is fleshy, the terminal is at the bladder neck without exception, and vesical trigone has relatively obvious three layers of structure. After dyeing dog’s bladder was transparent jelly, the nerve was purple color, enter bladder at the ureter-bladder junction with different forms. Man’s bladder nerves, no ganglion, were more trivial than that of dogs, and with smaller branches, the large nerve ganglion. The links with the nerve fibers and forms the network on the dog’s bladder wall, and the nerve fibers crosses comparatively little on both the left and right sides in the midline. The right nerve branch gains advantage on the man’s bladder wall, the situations is opposite on the dog’s. In conclusion, bladder nerves which scatter to the bladder wall have branches to lower ureter at the ureter-bladder junction, the structure and distribution of intramuscular nerves are different, the existence of intramuscular ganglia is relating to the bladder function both in man and dog. PMID:25664008

  4. Bidirectional Plasticity in Striatonigral Synapses: A Switch to Balance Direct and Indirect Basal Ganglia Pathways

    ERIC Educational Resources Information Center

    Aceves, Jose J.; Rueda-Orozco, Pavel E.; Hernandez-Martinez, Ricardo; Galarraga, Elvira; Bargas, Jose

    2011-01-01

    There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral…

  5. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

    PubMed Central

    Flegel, Caroline; Schöbel, Nicole; Altmüller, Janine; Becker, Christian; Tannapfel, Andrea; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq) to conduct the first expression analysis of human trigeminal ganglia (TG) and dorsal root ganglia (DRG). We analyzed the data with a focus on G-protein coupled receptors (GPCRs) and ion channels, which are (potentially) involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP) channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs) with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues. PMID:26070209

  6. Effects of Focal Basal Ganglia Lesions on Timing and Force Control

    ERIC Educational Resources Information Center

    Aparicio, P.; Diedrichsen, J.; Ivry, R.B.

    2005-01-01

    Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of…

  7. Stereotactic radiosurgery for deep intracranial arteriovenous malformations, part 2: Basal ganglia and thalamus arteriovenous malformations.

    PubMed

    Cohen-Inbar, Or; Ding, Dale; Sheehan, Jason P

    2016-02-01

    The aim of this review is to critically analyze the outcomes following stereotactic radiosurgery (SRS) for arteriovenous malformations (AVM) of the basal ganglia and thalamus. The management of these deep-seated lesions continues to challenge neurosurgeons. Basal ganglia and thalamic AVM show a higher risk of hemorrhage, and an associated devastating morbidity and mortality, as compared to AVM in more superficial locations. Any of the currently available treatment modalities may fail or result in iatrogenic neurologic deterioration. Recent evidence from A Randomized Trial of Unruptured Brain AVM (ARUBA) further deters aggressive approaches that carry a significant risk of treatment-related adverse events. Microsurgical resection, endovascular embolization and SRS all play a role in the treatment of AVM. SRS is an effective therapeutic option for AVM of the thalamus and basal ganglia that are deemed high risk for resection. SRS offers acceptable obliteration rates, with generally lower risks of hemorrhage occurring during the latency period compared to the AVM natural history. Considering that incompletely obliterated lesions still harbor the potential for rupture, additional treatments such as repeat SRS and microsurgical resection should be considered when complete obliteration is not achieved by an initial SRS procedure. Patients with AVM of the basal ganglia and thalamus require continued clinical and radiologic observation and follow-up after SRS, even after angiographic obliteration has been confirmed. PMID:26732284

  8. [Distinct roles of the direct and indirect pathways in the basal ganglia circuit mechanism].

    PubMed

    Morita, Makiko; Hikida, Takatoshi

    2015-11-01

    The basal ganglia are key neural substrates that control not only motor balance but also emotion, motivation, cognition, learning, and decision-making. Dysfunction of the basal ganglia leads to neurodegenerative diseases (e.g. Parkinson's disease and Huntington's disease) and psychiatric disorders (e.g. drug addiction, schizophrenia, and depression). In the basal ganglia circuit, there are two important pathways: the direct and indirect striatal pathways. Recently, new molecular techniques that activate or inactive selectively the direct or indirect pathway neurons have revealed the function of each pathway. Here we review the distinct roles of the direct and indirect striatal pathways in brain function and drug addiction. We have developed a reversible neurotransmission blocking technique, in which transmission of each pathway is selectively blocked by specific expression of transmission-blocking tetanus toxin, and revealed that the activation of D1 receptors in the direct pathway is critical for reward learning/cocaine addiction, and that the inactivation of D2 receptors is critical for aversive learning/learning flexibility. We propose a new circuit mechanism by which the dopaminergic input from the ventral tegmental area can switch the direct and indirect pathways in the nucleus accumbens. These basal ganglia circuit mechanisms will give us insights into the pathophysiology of mental diseases. PMID:26785520

  9. Differential contributions of basal ganglia and thalamus to song initiation, tempo, and structure.

    PubMed

    Chen, J R; Stepanek, L; Doupe, A J

    2014-01-01

    Basal ganglia-thalamocortical circuits are multistage loops critical to motor behavior, but the contributions of individual components to overall circuit function remain unclear. We addressed these issues in a songbird basal ganglia-thalamocortical circuit (the anterior forebrain pathway, AFP) specialized for singing and critical for vocal plasticity. The major known afferent to the AFP is the premotor cortical nucleus, HVC. Surprisingly, previous studies found that lesions of HVC alter song but do not eliminate the ability of the AFP to drive song production. We therefore used this AFP-driven song to investigate the role of basal ganglia and thalamus in vocal structure, tempo, and initiation. We found that lesions of the striatopallidal component (Area X) slowed song and simplified its acoustic structure. Elimination of the thalamic component (DLM) further simplified the acoustic structure of song and regularized its rhythm but also dramatically reduced song production. The acoustic structure changes imply that sequential stages of the AFP each add complexity to song, but the effects of DLM lesions on song initiation suggest that thalamus is a locus of additional inputs important to initiation. Together, our results highlight the cumulative contribution of stages of a basal ganglia-thalamocortical circuit to motor output along with distinct involvement of thalamus in song initiation or "gating." PMID:24174647

  10. Bidirectional Plasticity in Striatonigral Synapses: A Switch to Balance Direct and Indirect Basal Ganglia Pathways

    ERIC Educational Resources Information Center

    Aceves, Jose J.; Rueda-Orozco, Pavel E.; Hernandez-Martinez, Ricardo; Galarraga, Elvira; Bargas, Jose

    2011-01-01

    There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral…

  11. Acute movement disorder with bilateral basal ganglia lesions in diabetic uremia

    PubMed Central

    Wali, Gurusidheshwar M.; Khanpet, Mallikarjun S.; Mali, Rajendra V.

    2011-01-01

    Acute movement disorder associated with symmetrical basal ganglia lesions occurring in the background of diabetic end stage renal disease is a recently described condition. It has distinct clinico-radiological features and is commonly described in Asian patients. We report the first Indian case report of this potentially reversible condition and discuss its various clinico-radiological aspects. PMID:22028539

  12. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  13. The Role of the Basal Ganglia in Implicit Contextual Learning: A Study of Parkinson's Disease

    ERIC Educational Resources Information Center

    van Asselen, Marieke; Almeida, Ines; Andre, Rui; Januario, Cristina; Goncalves, Antonio Freire; Castelo-Branco, Miguel

    2009-01-01

    Implicit contextual learning refers to the ability to memorize contextual information from our environment. This contextual information can then be used to guide our attention to a specific location. Although the medial temporal lobe is important for this type of learning, the basal ganglia might also be involved considering its role in many…

  14. The Role of the Basal Ganglia in Implicit Contextual Learning: A Study of Parkinson's Disease

    ERIC Educational Resources Information Center

    van Asselen, Marieke; Almeida, Ines; Andre, Rui; Januario, Cristina; Goncalves, Antonio Freire; Castelo-Branco, Miguel

    2009-01-01

    Implicit contextual learning refers to the ability to memorize contextual information from our environment. This contextual information can then be used to guide our attention to a specific location. Although the medial temporal lobe is important for this type of learning, the basal ganglia might also be involved considering its role in many…

  15. Visuo-Motor and Cognitive Procedural Learning in Children with Basal Ganglia Pathology

    ERIC Educational Resources Information Center

    Mayor-Dubois, C.; Maeder, P.; Zesiger, P.; Roulet-Perez, E.

    2010-01-01

    We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (less than 1 year old, n=9), later…

  16. [A Role of the Basal Ganglia in Processing of Complex Sounds and Auditory Attention].

    PubMed

    Silkis, I G

    2015-01-01

    A hypothetical mechanism is suggested for processing of complex sounds and auditory attention in parallel neuronal loops including various auditory cortical areas connected with parts of the medial geniculate body, inferior colliculus and basal ganglia. Release of dopamine in the striatum promotes bidirectional modulation of strong and weak inputs from the neocortex to striatal neurons giving rise to direct and indirect pathways through the basal ganglia. Subsequent synergistic disinhibition of one and inhibition of other groups of thalamic neurons by the basal ganglia result in the creation of contrasted neuronal representations of properties of auditory stimuli in related cortical areas. Contrasting is strengthened due to a simultaneous disinhibition of pedunculopontine nucleus and action at muscarine receptors on neurons in the medial geniculate body. It follows from this mechanism that involuntary attention to sound tone can enhance an early component of the responses of neurons in the primary auditory cortical area (50 msec) in the absence of dopamine due to a disinhibition of thalamic neurons via the direct pathway through the basal ganglia, whereas voluntary attention to complex sounds can enhance only those components of responses of neurones in secondary auditory cortical areas which latencies exceeds latencies of dopaminergic cells (i.e. after 100 msec). Various consequences of proposed mechanism are in agreement with known experimental data. PMID:26506644

  17. Differential contributions of basal ganglia and thalamus to song initiation, tempo, and structure

    PubMed Central

    Chen, J. R.; Doupe, A. J.

    2013-01-01

    Basal ganglia-thalamocortical circuits are multistage loops critical to motor behavior, but the contributions of individual components to overall circuit function remain unclear. We addressed these issues in a songbird basal ganglia-thalamocortical circuit (the anterior forebrain pathway, AFP) specialized for singing and critical for vocal plasticity. The major known afferent to the AFP is the premotor cortical nucleus, HVC. Surprisingly, previous studies found that lesions of HVC alter song but do not eliminate the ability of the AFP to drive song production. We therefore used this AFP-driven song to investigate the role of basal ganglia and thalamus in vocal structure, tempo, and initiation. We found that lesions of the striatopallidal component (Area X) slowed song and simplified its acoustic structure. Elimination of the thalamic component (DLM) further simplified the acoustic structure of song and regularized its rhythm but also dramatically reduced song production. The acoustic structure changes imply that sequential stages of the AFP each add complexity to song, but the effects of DLM lesions on song initiation suggest that thalamus is a locus of additional inputs important to initiation. Together, our results highlight the cumulative contribution of stages of a basal ganglia-thalamocortical circuit to motor output along with distinct involvement of thalamus in song initiation or “gating.” PMID:24174647

  18. The disrupted basal ganglia and behavioural control: an integrative cross-domain perspective of spontaneous stereotypy.

    PubMed

    McBride, Sebastian D; Parker, Matthew O

    2015-01-01

    Spontaneous stereotypic behaviour (SB) is common in many captive animal species, as well as in humans with some severe psychiatric disorders, and is often cited as being related to general basal ganglia dysfunction. Despite this assertion, there is little in the literature examining SB specifically in terms of the basal ganglia mechanics. In this review, we attempt to fill this gap by offering an integrative, cross-domain perspective of SB by linking what we currently understand about the SB phenotype with the ever-growing literature on the anatomy and functionality of the basal ganglia. After outlining current models of SB from different theoretical perspectives, we offer a broad but detailed overview of normally functioning basal ganglia mechanics, and attempt to link this with current neurophysiological evidence related to spontaneous SB. Based on this we present an empirically derived theoretical framework, which proposes that SB is the result of a dysfunctional action selection system that may reflect dysregulation of excitatory (direct) and inhibitory (indirect and hyperdirect) pathways as well as alterations in mechanisms of behavioural switching. This approach also suggests behaviours that specifically become stereotypic may reflect inbuilt low selection threshold behavioural sequences associated with early development and the species-specific ethogram or, low threshold behavioural sequences that are the result of stress-induced dopamine exposure at the time of performance. PMID:25052167

  19. How may the basal ganglia contribute to auditory categorization and speech perception?

    PubMed Central

    Lim, Sung-Joo; Fiez, Julie A.; Holt, Lori L.

    2014-01-01

    Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language-specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood. PMID:25136291

  20. The Differential Effects of Thalamus and Basal Ganglia on Facial Emotion Recognition

    ERIC Educational Resources Information Center

    Cheung, Crystal C. Y.; Lee, Tatia M. C.; Yip, James T. H.; King, Kristin E.; Li, Leonard S. W.

    2006-01-01

    This study examined if subcortical stroke was associated with impaired facial emotion recognition. Furthermore, the lateralization of the impairment and the differential profiles of facial emotion recognition deficits with localized thalamic or basal ganglia damage were also studied. Thirty-eight patients with subcortical strokes and 19 matched…

  1. Normal and abnormal thymus in childhood: MR imaging.

    PubMed

    Siegel, M J; Glazer, H S; Wiener, J I; Molina, P L

    1989-08-01

    Magnetic resonance (MR) imaging studies of 47 children without thymic disease were compared with those of 14 children with proved thymic abnormalities (eg, lymphoma, leukemia, hyperplasia) to evaluate the spectrum of MR features of the normal and abnormal thymus and to determine the best indicators of thymic disease. In healthy children younger than 5 years of age, the thymus had a quadrilateral shape and biconvex lateral contours. Older children and adolescents had a triangular thymus with straight lateral margins. The thymus appeared homogeneous with a signal intensity slightly greater than that of muscle on T1-weighted images and close to that of fat on T2-weighted images. Qualitative evaluation of gross thymic morphology (size, shape, margins, and signal intensity) usually was sufficient for distinguishing between the normal and abnormal thymus. The abnormal thymus generally was enlarged, multilobular, or inhomogeneous because of the presence of cystic degeneration, hemorrhage, septations, fibrosis, or calcification on pathologic sections. In patients with lymphoma, the presence of associated lymphadenopathy also was helpful in distinguishing the normal from the abnormal thymus. PMID:2748817

  2. Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia.

    PubMed

    Mawe, G M; Talmage, E K; Cornbrooks, E B; Gokin, A P; Zhang, L; Jennings, L J

    1997-10-01

    The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin (CCK) acts presynaptically within gallbladder ganglia to increase the release of acetylcholine from vagal terminals. Results reported here indicate that hormonal CCK can readily access gallbladder ganglia, since there is no evidence for a blood-ganglionic barrier in the gallbladder. Taken together, these results indicate that gallbladder ganglia are not simple relay stations, but rather sites of complex modulatory interactions that ultimately influence the functions of muscle and epithelial cells in the organ. PMID:9329015

  3. Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue

    PubMed Central

    Miller, Andrew H.; Jones, James F.; Drake, Daniel F.; Tian, Hao; Unger, Elizabeth R.; Pagnoni, Giuseppe

    2014-01-01

    Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation. In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling) task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses. Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects. These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks. PMID:24858857

  4. Neural basis of singing in crickets: central pattern generation in abdominal ganglia

    NASA Astrophysics Data System (ADS)

    Schöneich, Stefan; Hedwig, Berthold

    2011-12-01

    The neural mechanisms underlying cricket singing behavior have been the focus of several studies, but the central pattern generator (CPG) for singing has not been localized conclusively. To test if the abdominal ganglia contribute to the singing motor pattern and to analyze if parts of the singing CPG are located in these ganglia, we systematically truncated the abdominal nerve cord of fictively singing crickets while recording the singing motor pattern from a front-wing nerve. Severing the connectives anywhere between terminal ganglion and abdominal ganglion A3 did not preclude singing, although the motor pattern became more variable and failure-prone as more ganglia were disconnected. Singing terminated immediately and permanently after transecting the connectives between the metathoracic ganglion complex and the first unfused abdominal ganglion A3. The contribution of abdominal ganglia for singing pattern generation was confirmed by intracellular interneuron recordings and current injections. During fictive singing, an ascending interneuron with its soma and dendrite in A3 depolarized rhythmically. It spiked 10 ms before the wing-opener activity and hyperpolarized in phase with the wing-closer activity. Depolarizing current injection elicited rhythmic membrane potential oscillations and spike bursts that elicited additional syllables and reliably reset the ongoing chirp rhythm. Our results disclose that the abdominal ganglion A3 is directly involved in generating the singing motor pattern, whereas the more posterior ganglia seem to provide only stabilizing feedback to the CPG circuit. Localizing the singing CPG in the anterior abdominal neuromeres now allows analyzing its circuitry at the level of identified interneurons in subsequent studies.

  5. Neuroanatomical Correlates of Intelligence in Healthy Young Adults: The Role of Basal Ganglia Volume

    PubMed Central

    Rhein, Cosima; Mühle, Christiane; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Doerfler, Arnd; Kornhuber, Johannes

    2014-01-01

    Background In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions. Methodology/Principal Findings We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur-Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor; in females, the pallidum volumes were correlated with crystallised figural intelligence (r?=?0.372, p?=?0.01), whereas in males, the caudate volumes were correlated with fluid figural intelligence (r?=?0.507, p?=?0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r?=?0.306, p?=?0.04 and r?=?0.459, p?=?0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses. Conclusions/Significance The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia nuclei in a sex-specific manner. Subcortical brain structures thus may contribute substantially to cognitive performance. PMID:24699871

  6. Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements

    PubMed Central

    Bednark, Jeffery G.; Campbell, Megan E. J.; Cunnington, Ross

    2015-01-01

    Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g., rhythm) and ordinal motor processes. Using high-resolution functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA), we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the supplementary motor area (SMA) and basal-ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia. PMID:26283945

  7. Complex patterns of abnormal heartbeats

    NASA Technical Reports Server (NTRS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

    2002-01-01

    Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

  8. Endoscopic Evacuation of Basal Ganglia Hemorrhage via Keyhole Approach Using an Adjustable Cannula in Comparison with Craniotomy

    PubMed Central

    Zhang, Heng-Zhu; Li, Yu-Ping; Yan, Zheng-cun; Wang, Xing-dong; She, Lei; Wang, Xiao-dong; Dong, Lun

    2014-01-01

    Neuroendoscopic (NE) surgery as a minimal invasive treatment for basal ganglia hemorrhage is a promising approach. The present study aims to evaluate the efficacy and safety of NE approach using an adjustable cannula to treat basal ganglia hemorrhage. In this study, we analysed the clinical and radiographic outcomes between NE group (21 cases) and craniotomy group (30 cases). The results indicated that NE surgery might be an effective and safe approach for basal ganglia haemorrhage, and it is also suggested that NE approach may improve good functional recovery. However, NE approach only suits the selected patient, and the usefulness of NE approach needs further randomized controlled trials (RCTs) to evaluate. PMID:24949476

  9. Abnormalities of the external genitalia.

    PubMed

    Baldinger, Lauren; Mudegowdar, Abhijith; Shukla, Aseem R

    2014-09-01

    Abnormalities of the external genitalia span the spectrum from subtle findings of limited clinical significance to profound anomalies that call into question such essential questions as sex determination. In addition, missing a diagnosis of congenital adrenal hyperplasia in a newborn female child with virilized external genitalia can result in near-term mortality, whereas a large inguinal hernia could present rapidly with incarceration if undetected. To that end, this article seeks to present a survey of commonly encountered genital abnormalities while highlighting those scenarios that require multidisciplinary interventions. PMID:25155737

  10. Brain white matter volume abnormalities in Lesch-Nyhan disease and its variants

    PubMed Central

    Varvaris, Mark; Vannorsdall, Tracy D.; Gordon, Barry; Harris, James C.; Jinnah, H.A.

    2015-01-01

    Objective: We sought to examine brain white matter abnormalities based on MRI in adults with Lesch-Nyhan disease (LND) or an attenuated variant (LNV) of this rare, X-linked neurodevelopmental disorder of purine metabolism. Methods: In this observational study, we compared 21 adults with LND, 17 with LNV, and 33 age-, sex-, and race-matched healthy controls using voxel-based morphometry and analysis of covariance to identify white matter volume abnormalities in both patient groups. Results: Patients with classic LND showed larger reductions of white (26%) than gray (17%) matter volume relative to healthy controls. Those with LNV showed comparable reductions of white (14%) and gray (15%) matter volume. Both patient groups demonstrated reduced volume in medial inferior white matter regions. Compared with LNV, the LND group showed larger reductions in inferior frontal white matter adjoining limbic and temporal regions and the motor cortex. These regions likely include such long association fibers as the superior longitudinal and uncinate fasciculi. Conclusions: Despite earlier reports that LND primarily involves the basal ganglia, this study reveals substantial white matter volume abnormalities. Moreover, white matter deficits are more severe than gray matter deficits in classic LND, and also characterize persons with LNV. The brain images acquired for these analyses cannot precisely localize white matter abnormalities or determine whether they involve changes in tract orientation or anisotropy. However, clusters of reduced white matter volume identified here affect regions that are consistent with the neurobehavioral phenotype. PMID:25503620

  11. Fiber formation and myelinization of cultivated dissociated neurons from chicken dorsal root ganglia: an electron microscopic and scanning electron microscopic study.

    PubMed

    Lodin, Z; Faltin, J; Booher, J; Hartman, J; Sensenbrenner, M

    1973-01-01

    Dissociated neurons from chicken embryo dorsal root ganglia were cultivated in Rose chambers for up to 5 weeks. Newly formed fibers appeared as single fibers or grouped in bundles. During the first week of cultivation microtubules and microfilaments were frequently observed. The diameters of the fibers increased progressively and a number of varicosities appeared. In some distal portions of fibers large vesicles could be observed. During the second week in culture Schwann cells were easily recognized. They appeared as both dark and light cells. During this period myelinization of some fibers was seen to commence. High glucose concentrations were not observed to influence the process of myelinization. Essentially the important factors were the number of cells present in the culture and also the presence of NGF in the medium. Schwann cells myelinated nerve fibers exclusively. Two types of abnormalities in myelin formation were recognized: one Schwann cell myelinating two fibers and one fiber being myelinated twice, by two Schwann cells. Concomitantly with myelinization, myelin degeneration was observed. Histiotypic fascicles, typical constituents of the outgrowth zone of cultivated intact dorsal root ganglia, bundles of fibers, surrounded by connective tissue, are not formed. The surface ultrastructure of nerve fibers, as studied by scanning EM, was seen to be covered by numerous spherical elements as well as by small fibers and irregular elements. The growth cones of fibers were void of any glial contact. Myelinization occupied individual isolated segments along with nerve fibers and evidenced the absence of nodes of Ranvier. Relationships between single elements in the dissociated culture system are discussed, with respect to the possibilities for analysis of some of the elementary mechanisms of cellular and molecular interaction responsible for the development of the peripheral nervous system. PMID:16100956

  12. Oral-oesophageal inoculation of mice with herpes simplex virus type 1 causes latent infection of the vagal sensory ganglia (nodose ganglia).

    PubMed

    Gesser, R M; Valyi-Nagy, T; Altschuler, S M; Fraser, N W

    1994-09-01

    Herpes simplex virus type 1 (HSV-1) gingivostomatitis during childhood is known to result in a latent infection of the trigeminal ganglion neurons, which innervate the oral mucosa. During latency the viral genome is maintained in a non-infectious state. However, stimuli such as stress, fever or localized trauma can cause HSV-1 to reactivate in neurons and produce recrudescent disease in the peripheral tissues. Recently, HSV-1 proteins and nucleic acids have been detected in biopsies from human duodenal and gastric ulcers, raising the possibility that HSV-1 latency within the enteric nervous system is involved in this chronic recurrent gastrointestinal disorder. The studies in mice described here were done to determine whether HSV-1 latency could be established in neurons that innervate the murine gut. We found that after either intraperitoneal or oral-oesophageal inoculation of mice, HSV-1 establishes a latent infection in nodose ganglia of the vagus nerve, whose sensory neurons project to the gastrointestinal tract. This animal model of HSV-1 latency in the vagal sensory ganglia will be useful to examine the possible relationship between HSV-1 and recurrent gastrointestinal disease. PMID:8077936

  13. Electrocardiograph abnormalities in intracerebral hemorrhage.

    PubMed

    Takeuchi, Satoru; Nagatani, Kimihiro; Otani, Naoki; Wada, Kojiro; Mori, Kentaro

    2015-12-01

    This study investigated the prevalence and type of electrocardiography (ECG) abnormalities, and their possible association with the clinical/radiological findings in 118 consecutive patients with non-traumatic, non-neoplastic intracerebral hemorrhage (ICH). ECG frequently demonstrates abnormalities in patients with ischemic stroke and subarachnoid hemorrhage, but little is known of ECG changes in ICH patients. Clinical and radiological information was retrospectively reviewed. ECG recordings that were obtained within 24hours of the initial hemorrhage were analyzed. Sixty-six patients (56%) had one or more ECG abnormalities. The most frequent was ST depression (24%), followed by left ventricular hypertrophy (20%), corrected QT interval (QTc) prolongation (19%), and T wave inversion (19%). The logistic regression analysis demonstrated the following: insular involvement was an independent predictive factor of ST depression (p<0.001; odds ratio OR 10.18; 95% confidence interval [CI] 2.84-36.57); insular involvement (p<0.001; OR 23.98; 95% CI 4.91-117.11) and presence of intraventricular hemorrhage (p<0.001; OR 8.72; 95% CI 2.69-28.29) were independent predictive factors of QTc prolongation; deep hematoma location (p<0.001; OR 19.12; 95% CI 3.82-95.81) and hematoma volume >30ml (p=0.001; OR 6.58; 95% CI 2.11-20.46) were independent predictive factors of T wave inversion. We demonstrate associations between ECG abnormalities and detailed characteristics of ICH. PMID:26365482

  14. Postural Abnormalities: An Individualized Program.

    ERIC Educational Resources Information Center

    Vodola, Thomas M.

    As one of the components of the Project ACTIVE (All Children Totally Involved Exercising) Teacher Training Model Kit, the manual is designed to enable the educator to organize, conduct, and evaluate individualized-personalized programs for children in grades 4 through 12 with postural abnormalities. An introductory chapter covers definitions and…

  15. Interpreting chromosomal abnormalities using Prolog.

    PubMed

    Cooper, G; Friedman, J M

    1990-04-01

    This paper describes an expert system for interpreting the standard notation used to represent human chromosomal abnormalities, namely, the International System for Human Cytogenetic Nomenclature. Written in Prolog, this program is very powerful, easy to maintain, and portable. The system can be used as a front end to any database that employs cytogenetic notation, such as a patient registry. PMID:2185921

  16. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease

    SciTech Connect

    Akiyama, H.; Harrop, R.; McGeer, P.L.; Peppard, R.; McGeer, E.G.

    1989-04-01

    We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using /sup 18/F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices, while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis.

  17. Competing basal ganglia pathways determine the difference between stopping and deciding not to go.

    PubMed

    Dunovan, Kyle; Lynch, Brighid; Molesworth, Tara; Verstynen, Timothy

    2015-01-01

    The architecture of corticobasal ganglia pathways allows for many routes to inhibit a planned action: the hyperdirect pathway performs fast action cancellation and the indirect pathway competitively constrains execution signals from the direct pathway. We present a novel model, principled off of basal ganglia circuitry, that differentiates control dynamics of reactive stopping from intrinsic no-go decisions. Using a nested diffusion model, we show how reactive braking depends on the state of an execution process. In contrast, no-go decisions are best captured by a failure of the execution process to reach the decision threshold due to increasing constraints on the drift rate. This model accounts for both behavioral and functional MRI (fMRI) responses during inhibitory control tasks better than alternative models. The advantage of this framework is that it allows for incorporating the effects of context in reactive and proactive control into a single unifying parameter, while distinguishing action cancellation from no-go decisions. PMID:26402462

  18. Evidence for a causal inverse model in an avian cortico-basal ganglia circuit

    PubMed Central

    Giret, Nicolas; Kornfeld, Joergen; Ganguli, Surya; Hahnloser, Richard H. R.

    2014-01-01

    Learning by imitation is fundamental to both communication and social behavior and requires the conversion of complex, nonlinear sensory codes for perception into similarly complex motor codes for generating action. To understand the neural substrates underlying this conversion, we study sensorimotor transformations in songbird cortical output neurons of a basal-ganglia pathway involved in song learning. Despite the complexity of sensory and motor codes, we find a simple, temporally specific, causal correspondence between them. Sensory neural responses to song playback mirror motor-related activity recorded during singing, with a temporal offset of roughly 40 ms, in agreement with short feedback loop delays estimated using electrical and auditory stimulation. Such matching of mirroring offsets and loop delays is consistent with a recent Hebbian theory of motor learning and suggests that cortico-basal ganglia pathways could support motor control via causal inverse models that can invert the rich correspondence between motor exploration and sensory feedback. PMID:24711417

  19. Balanced activity in basal ganglia projection pathways is critical for contraversive movements

    PubMed Central

    Tecuapetla, Fatuel; Matias, Sara; Dugue, Guillaume P.; Mainen, Zachary F.; Costa, Rui M.

    2014-01-01

    The basal ganglia, and the striatum in particular, have been implicated in the generation of contraversive movements. The striatum projects to downstream basal ganglia nuclei through two main circuits, originating in striatonigral and striatopallidal neurons, and different models postulate that the two pathways can work in opposition or synergistically. Here we show striatonigral and striatopallidal neurons are concurrently active during spontaneous contraversive movements. Furthermore, we show that unilateral optogenetic inhibition of either or both projection pathways disrupts contraversive movements. Consistently, simultaneous activation of both neuron types produces contraversive movements. Still, we also show that imbalanced activity between the pathways can result in opposing movements being driven by each projection pathway. These data show that balanced activity in both striatal projection pathways is critical for the generation of contraversive movements and highlights that imbalanced activity between the two projection pathways can result in opposing motor output. PMID:25002180

  20. Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy

    PubMed Central

    Schroll, Henning; Hamker, Fred H.

    2013-01-01

    Over the past 15 years, computational models have had a considerable impact on basal-ganglia research. Most of these models implement multiple distinct basal-ganglia pathways and assume them to fulfill different functions. As there is now a multitude of different models, it has become complex to keep track of their various, sometimes just marginally different assumptions on pathway functions. Moreover, it has become a challenge to oversee to what extent individual assumptions are corroborated or challenged by empirical data. Focusing on computational, but also considering non-computational models, we review influential concepts of pathway functions and show to what extent they are compatible with or contradict each other. Moreover, we outline how empirical evidence favors or challenges specific model assumptions and propose experiments that allow testing assumptions against each other. PMID:24416002

  1. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

    PubMed Central

    Haagensen, Brian N.; Christensen, Mark S.; Madsen, Kristoffer H.; Rowe, James B.; Løkkegaard, Annemette; Siebner, Hartwig R.

    2015-01-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51–84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements. PMID:25882651

  2. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans.

    PubMed

    Herz, Damian M; Haagensen, Brian N; Christensen, Mark S; Madsen, Kristoffer H; Rowe, James B; Løkkegaard, Annemette; Siebner, Hartwig R

    2015-06-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51-84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements. PMID:25882651

  3. Quantifying the abnormal hemodynamics of sickle cell anemia

    NASA Astrophysics Data System (ADS)

    Lei, Huan; Karniadakis, George

    2012-02-01

    Sickle red blood cells (SS-RBC) exhibit heterogeneous morphologies and abnormal hemodynamics in deoxygenated states. A multi-scale model for SS-RBC is developed based on the Dissipative Particle Dynamics (DPD) method. Different cell morphologies (sickle, granular, elongated shapes) typically observed in deoxygenated states are constructed and quantified by the Asphericity and Elliptical shape factors. The hemodynamics of SS-RBC suspensions is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. Moreover, SS-RBCs exhibit abnormal adhesive interactions with both the vessel endothelium cells and the leukocytes. The effect of the abnormal adhesive interactions on the hemodynamics of sickle blood is investigated using the current model. It is found that both the SS-RBC - endothelium and the SS-RBC - leukocytes interactions, can potentially trigger the vicious ``sickling and entrapment'' cycles, resulting in vaso-occlusion phenomena widely observed in micro-circulation experiments.

  4. Metabolic and electrophysiological changes in the basal ganglia of transgenic Huntington's disease rats.

    PubMed

    Vlamings, Rinske; Benazzouz, Abdelhamid; Chetrit, Jonathan; Janssen, Marcus L F; Kozan, Ramazan; Visser-Vandewalle, Veerle; Steinbusch, Harry W M; von Hörsten, Stephan; Temel, Yasin

    2012-12-01

    Huntington's disease (HD) is characterized by neuronal loss in the striatum, ultimately leading to an 'imbalance' in the electrical activity of the basal ganglia-thalamocortical circuits. To restore this 'imbalance' in HD patients, which is held responsible for (some) of the motor symptoms, different basal ganglia nuclei have been targeted for surgical therapies, such as ablative surgery and deep brain stimulation. However, evidence to target brain nuclei for surgical therapies in HD is lacking. We reasoned that a neuronal and metabolic mapping of the basal ganglia nuclei could identify a functional substrate for therapeutic interventions. Therefore, the aim of the present study was to investigate the metabolic and neuronal activity of basal ganglia nuclei in a transgenic rat model of HD (tgHD). Subjects were 10-12 month old tgHD rats and wildtype littermates. We examined the striatum, globus pallidus, entopeduncular nucleus, the subthalamic nucleus and substantia nigra at different levels. First, we determined the overall neuronal activity at a supracellular level, by cytochrome oxidase histochemistry. Secondly, we determined the subcellular metabolic activity, by immunohistochemistry for peroxisome proliferator-activated receptor-γ transcription co-activator (PGC-1α), a key player in the mitochondrial machinery. Finally, we performed extracellular single unit recordings in the nuclei to determine the cellular activity. In tgHD rats, optical density analysis showed a significantly increased cytochrome oxidase levels in the globus pallidus and subthalamic nucleus when compared to controls. PGC-1α expression was only enhanced in the subthalamic nucleus and electrophysiological recordings revealed decreased firing frequency of the majority of the neurons in the globus pallidus and increased firing frequency of the majority of the neurons in the subthalamic nucleus. Altogether, our results suggest that the globus pallidus and subthalamic nucleus play a role in the neurobiology of HD and can be potential targets for therapeutic interventions. PMID:22813864

  5. Functional properties of the basal ganglia's re-entrant loop architecture: selection and reinforcement.

    PubMed

    Redgrave, P; Vautrelle, N; Reynolds, J N J

    2011-12-15

    Multifunctional agents with limited motor resources must decide what actions will best ensure their survival. Moreover, given that in an unpredictable world things don't always work out, considerable advantage is to be gained by learning from experience - instrumental behaviour that maximises reward and minimises punishment. In this review we will argue that the re-entrant looped architecture of the basal ganglia represents biological solutions to these fundamental behavioural problems of selection and reinforcement. A potential solution to the selection problem is provided for by selective disinhibition within the parallel loop architecture that connects the basal ganglia with external neural structures. The relay points within these loops permit the signals of a particular channel to be modified by external influences. In part, these influences have the capacity to modify overall selections so that the probability of re-selecting reinforced behaviours in the future is altered. This is the basic process of instrumental learning, which we suggest decomposes into two sub-problems for the agent: (i) learning which external events it causes to happen and learning precisely what it is doing that is causal; and (ii) having determined agency and discovered novel action-outcome routines, how best to exploit this knowledge to maximise future reward acquisitions. Considerations of connectional architecture and signal timing suggest that the short-latency, sensory-evoked dopamine response, which can modulate the re-entrant loop structure within the basal ganglia, is ideally suited to reinforce the determination of agency and the discovery of novel actions. Alternatively, recent studies showing that presence or absence of reward can selectively modulate the magnitude of signals in structures providing input signals to the basal ganglia, offer an alternative mechanism for biasing selection within the re-entrant loop architecture. We suggest that this mechanism may be better suited to ensure the prioritisation of inputs associated with reward. PMID:21821101

  6. Role of Basal Ganglia Circuits in Resisting Interference by Distracters: A swLORETA Study

    PubMed Central

    Bocquillon, Perrine; Bourriez, Jean-Louis; Palmero-Soler, Ernesto; Destée, Alain; Defebvre, Luc; Derambure, Philippe; Dujardin, Kathy

    2012-01-01

    Background The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear, despite the fact that the striatum interacts significantly with the frontal cortex via frontostriatal loops. One means of investigating the basal ganglia's contributions to attention is to examine the features of P300 components (i.e. amplitude, latency, and generators) in patients with basal ganglia damage (such as in Parkinson's disease (PD), in which attention is often impaired). Three-stimulus oddball paradigms can be used to study distracter-elicited and target-elicited P300 subcomponents. Methodology/Principal Findings In order to compare distracter- and target-elicited P300 components, high-density (128-channel) electroencephalograms were recorded during a three-stimulus visual oddball paradigm in 15 patients with early PD and 15 matched healthy controls. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were performed using SPM5® software. The swLORETA analyses showed that PD patients displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no significant differences in target-elicited P300 sources; this suggests dysfunction of the DLPF cortex when the executive frontostriatal loop is disrupted by basal ganglia damage. Conclusions/Significance Our results suggest that the cortical attention frontoparietal networks (mainly the dorsal one) are modulated by the basal ganglia. Disruption of this network in PD impairs resistance to distracters, which results in attention disorders. PMID:22470542

  7. The basal ganglia select the expected sensory input used for predictive coding

    PubMed Central

    Colder, Brian

    2015-01-01

    While considerable evidence supports the notion that lower-level interpretation of incoming sensory information is guided by top-down sensory expectations, less is known about the source of the sensory expectations or the mechanisms by which they are spread. Predictive coding theory proposes that sensory expectations flow down from higher-level association areas to lower-level sensory cortex. A separate theory of the role of prediction in cognition describes “emulations” as linked representations of potential actions and their associated expected sensation that are hypothesized to play an important role in many aspects of cognition. The expected sensations in active emulations are proposed to be the top-down expectation used in predictive coding. Representations of the potential action and expected sensation in emulations are claimed to be instantiated in distributed cortical networks. Combining predictive coding with emulations thus provides a theoretical link between the top-down expectations that guide sensory expectations and the cortical networks representing potential actions. Now moving to theories of action selection, the basal ganglia has long been proposed to select between potential actions by reducing inhibition to the cortical network instantiating the desired action plan. Integration of these isolated theories leads to the novel hypothesis that reduction in inhibition from the basal ganglia selects not just action plans, but entire emulations, including the sensory input expected to result from the action. Basal ganglia disinhibition is hypothesized to both initiate an action and also allow propagation of the action’s associated sensory expectation down towards primary sensory cortex. This is a novel proposal for the role of the basal ganglia in biasing perception by selecting the expected sensation, and initiating the top-down transmission of those expectations in predictive coding. PMID:26441627

  8. Responses of the Rat Basal Ganglia Neurotensin Systems to Low Doses of Methamphetamine

    PubMed Central

    Alburges, Mario E.; Hoonakker, Amanda J.; Cordova, Nathaniel M.; Robson, Christina M.; McFadden, Lisa M.; Martin, Amber L.; Hanson, Glen R.

    2014-01-01

    Rationale Administration of high doses of methamphetamine (METH) in a manner mimicking the bingeing patterns associated with abuse, reduces NT release and causes its accumulation and elevated NT levels in extrapyramidal structures by a D1 mechanism. The relevance of these findings to the therapeutic use of METH needs to be studied. Objectives The effect of low doses (comparable to that used for therapy) of METH on basal ganglia NT systems was examined and compared to high-dose and self-administration effects previously reported. Methods Rats were injected four times (2-h intervals) with either saline or low doses of METH (0.25, 0.50 or 1.00 mg/kg/s.c.). For the DA antagonist studies, animals were pretreated with a D1 (SCH23390) or D2 (eticlopride) antagonist 15 min prior to METH or saline treatments. Rats were sacrificed 5–48 h after last injection. Results METH at doses of 0.25 and 0.50, but not 1.00 mg/kg rapidly and briefly decreased NTLI concentration in all basal ganglia structures studied. In the posterior dorsal striatum, the reduction in NT level after low-dose METH appeared to be caused principally by D2 stimulation, but both D2 and D1 stimulation were required for the NT responses in the other basal ganglia regions. Conclusions A novel finding from the present study was that opposite to abuse-mimicking high doses of METH, the therapeutically relevant low-dose METH treatment reduced NT tissue levels likely reflecting an increase in NT release and a short-term depletion of the levels of this neuropeptide in basal ganglia structures. The possible significance is discussed. PMID:24522333

  9. Vocal learning, prosody, and basal ganglia: don't underestimate their complexity.

    PubMed

    Ravignani, Andrea; Martins, Mauricio; Fitch, W Tecumseh

    2014-12-01

    Ackermann et al.'s arguments in the target article need sharpening and rethinking at both mechanistic and evolutionary levels. First, the authors' evolutionary arguments are inconsistent with recent evidence concerning nonhuman animal rhythmic abilities. Second, prosodic intonation conveys much more complex linguistic information than mere emotional expression. Finally, human adults' basal ganglia have a considerably wider role in speech modulation than Ackermann et al. surmise. PMID:25514960

  10. Long-term depression at distinct glutamatergic synapses in the basal ganglia.

    PubMed

    Dupuis, Julien P; Bioulac, Bernard H; Baufreton, Jérôme

    2014-01-01

    Long-term adaptations of synaptic transmission are believed to be the cellular basis of information storage in the brain. In particular, long-term depression of excitatory neurotransmission has been under intense investigation since convergent lines of evidence support a crucial role for this process in learning and memory. Within the basal ganglia, a network of subcortical nuclei forming a key part of the extrapyramidal motor system, plasticity at excitatory synapses is essential to the regulation of motor, cognitive, and reward functions. The striatum, the main gateway of the basal ganglia, receives convergent excitatory inputs from cortical areas and transmits information to the network output structures and is a major site of activity-dependent plasticity. Indeed, long-term depression at cortico-striatal synapses modulates the transfer of information to basal ganglia output structures and affects voluntary movement execution. Cortico-striatal plasticity is thus considered as a cellular substrate for adaptive motor control. Downstream in this network, the subthalamic nucleus and substantia nigra nuclei also receive glutamatergic innervation from the cortex and the subthalamic nucleus, respectively. Although these connections have been less investigated, recent studies have started to unravel the molecular mechanisms that contribute to adjustments in the strength of cortico-subthalamic and subthalamo-nigral transmissions, revealing that adaptations at these synapses governing the output of the network could also contribute to motor planning and execution. Here, we review our current understanding of long-term depression mechanisms at basal ganglia glutamatergic synapses and emphasize the common and unique plastic features observed at successive levels of the network in healthy and pathological conditions. PMID:25046307

  11. [Depression and calcinosis of the basal ganglia: apropos of a case].

    PubMed

    Glück-Vanlaer, N; Fallet, A; Plas, J; Chevalier, J F

    1996-01-01

    Idiopathic basal ganglia calcifications is a heterogeneous entity characterized by the association of bilateral and symmetric calcifications of the basal ganglia and the dentae nuclei in the cerebellum, polymorphous neuropsychiatric symptomatology. It is rare, of unknown etiology and often hereditary. We report the case of a 48 years old man, who presented with melancholic depression which has been steadily worsening for more than a year and which had led to a serious suicide attempt. Clinical observation revealed apragmatism, affective dullness and impoverished spontaneous expression; the theme of incapacity predominated but guilt feelings were absent. Neurologic examination was normal except for extra-pyramidal signs. CT-scan revealed the presence of bilateral and extensive calcifications of caudate nuclei, lenticular nuclei and thalamus, which indicated a diagnosis of idiopathic basal ganglia calcification characterized by depression. Moreover, MRI revealed an hypersignal of the white periventricular substance. Phospho-calcic results and the parathormone dosage were normal. Psychometric tests showed that although intellectual capacity seemed to be intact, it was not utilised in practice. Unresponsive to antidepressants and sismotherapy, the patient is still the same one and a half year later, and needs to remain in an institution. Subsequent tests indicate that intellectual deterioration has begun. This case poses the problem of the relationship between depressive syndrome and basal ganglia lesions. We look at studies bearing on this subject and on other clinically similar syndromes (athymhormia, loss of psychic self-activation), in which the interruption or cortico-striato-pallido-thalamo-cortical circuits (particularly the limbic loop), is a physiopathologic mechanism currently invoked. PMID:8706622

  12. The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

    PubMed Central

    Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

    2010-01-01

    The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

  13. Oxaliplatin enhances gap junction-mediated coupling in cell cultures of mouse trigeminal ganglia.

    PubMed

    Poulsen, Jeppe Nørgaard; Warwick, Rebekah; Duroux, Meg; Hanani, Menachem; Gazerani, Parisa

    2015-08-01

    Communications between satellite glial cells and neighboring neurons within sensory ganglia may contribute to neuropathic and inflammatory pain. To elucidate the role of satellite glial cells in chemotherapy-induced pain, we examined the effects of oxaliplatin on the gap junction-mediated coupling between these cells. We also examined whether the gap junction blocker, carbenoxolone, can reverse the coupling. Primary cultures of mice trigeminal ganglia, 24-48h after cell isolation, were used. Satellite glial cells were injected with Lucifer yellow in the presence or absence of oxaliplatin (60 ?M). In addition, the effect of carbenoxolone (100 ?M) on coupling, and the expression of connexin 43 proteins were evaluated. Dye coupling between adjacent satellite glial cells was significantly increased (2.3-fold, P<0.05) following a 2h incubation with oxaliplatin. Adding carbenoxolone to the oxaliplatin-treated cultures reversed oxaliplatin-evoked coupling to baseline (P<0.05). Immunostaining showed no difference between expression of connexin 43 in control and oxaliplatin-treated cultures. Our findings indicated that oxaliplatin-increased gap junction-mediated coupling between satellite glial cells in primary cultures of mouse trigeminal ganglia, and carbenoxolone reversed this effect. Hence, it is proposed that increased gap junction-mediated coupling was seen between satellite glial cells in TG. This observation together with our previous data obtained from a behavioral study suggests that this phenomenon might contribute to chemotherapy-induced nociception following oxaliplatin treatment. PMID:25999145

  14. Evidence for Altered Basal Ganglia-Brainstem Connections in Cervical Dystonia

    PubMed Central

    Blood, Anne J.; Kuster, John K.; Woodman, Sandra C.; Kirlic, Namik; Makhlouf, Miriam L.; Multhaupt-Buell, Trisha J.; Makris, Nikos; Parent, Martin; Sudarsky, Lewis R.; Sjalander, Greta; Breiter, Henry

    2012-01-01

    Background There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia. Methodology/Principal Findings In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients. Conclusions/Significance These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia. PMID:22384048

  15. A minimally invasive anterior skull base approach for evacuation of a basal ganglia hemorrhage.

    PubMed

    Ding, Dale; Przybylowski, Colin J; Starke, Robert M; Sterling Street, R; Tyree, Amber E; Webster Crowley, R; Liu, Kenneth C

    2015-11-01

    We describe the technical nuances of a minimally invasive anterior skull base approach for microsurgical evacuation of a large basal ganglia hematoma through an endoport. Patients who suffer from large spontaneous intracerebral hemorrhages (ICH) of the basal ganglia have a very poor prognosis. However, the benefit of surgery for the management of ICH is controversial. The development of endoport technology has allowed for minimally invasive access to subcortical lesions, and may offer unique advantages over conventional surgical techniques due to less disruption of the overlying cortex and white matter fiber tracts. A 77-year-old man presented with a hypertensive ICH of the right putamen, measuring 9 cm in maximal diameter and 168 cm(3) in volume. We planned an endoport trajectory through the long axis of the hematoma using frameless stereotactic neuronavigation. In order to access the optimal cortical entry point at the lateral aspect of the basal frontal lobe, a miniature modified orbitozygomatic skull base craniotomy was performed through an incision along the superior border of the right eyebrow. Using the BrainPath endoport system (NICO, Indianapolis, IN, USA), the putaminal hematoma was successfully evacuated, resulting in an 87% postoperative reduction in ICH volume. Thus, we show that, in appropriately selected cases, endoport-assisted microsurgery is safe and effective for the evacuation of large ICH. Furthermore, minimally invasive anterior skull base approaches can be employed to expand the therapeutic potential of endoport-assisted approaches to include subcortical lesions, such as hematomas of the basal ganglia. PMID:26142050

  16. Brain tissue properties differentiate between motor and limbic basal ganglia circuits

    PubMed Central

    Accolla, Ettore A; Dukart, Juergen; Helms, Gunther; Weiskopf, Nikolaus; Kherif, Ferath; Lutti, Antoine; Chowdhury, Rumana; Hetzer, Stefan; Haynes, John-Dylan; Kühn, Andrea A; Draganski, Bogdan

    2014-01-01

    Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome. PMID:24777915

  17. A basal ganglia-forebrain circuit in the songbird biases motor output to avoid vocal errors

    PubMed Central

    Andalman, Aaron S.; Fee, Michale S.

    2009-01-01

    In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and production of complex motor behaviors; however, the precise role of these circuits remains unknown. It has recently been shown that a basal ganglia-forebrain circuit in the songbird, which projects directly to vocal–motor circuitry, has a premotor function driving exploration necessary for vocal learning. It has also been hypothesized that this circuit, known as the anterior forebrain pathway (AFP), may generate an instructive signal that improves performance in the motor pathway. Here, we show that the output of the AFP directly implements a motor correction that reduces vocal errors. We use disruptive auditory feedback, contingent on song pitch, to induce learned changes in song structure over the course of hours and find that reversible inactivation of the output of the AFP produces an immediate regression of these learned changes. Thus, the AFP is involved in generating an error-reducing bias, which could increase the efficiency of vocal exploration and instruct synaptic changes in the motor pathway. We also find that learned changes in the song generated by the AFP are incorporated into the motor pathway within 1 day. Our observations support a view that basal ganglia-related circuits directly implement behavioral adaptations that minimize errors and subsequently stabilize these adaptations by training premotor cortical areas. PMID:19597157

  18. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

    PubMed Central

    2015-01-01

    The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. PMID:25722894

  19. Satellite glial cells in dorsal root ganglia are activated in streptozotocin-treated rodents

    PubMed Central

    Hanani, Menachem; Blum, Erez; Liu, Shuangmei; Peng, Lichao; Liang, Shangdong

    2014-01-01

    Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ-treatment the number of neurons surrounded with GFAP-positive SGCs in dorsal root ganglia increased 4-fold in mice and 5-fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2-fold in STZ-treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target. PMID:25312986

  20. Independent circuits in the basal ganglia for the evaluation and selection of actions

    PubMed Central

    Stephenson-Jones, Marcus; Kardamakis, Andreas A.; Robertson, Brita; Grillner, Sten

    2013-01-01

    The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (GPh) neurons, exists within the basal ganglia. The GPh neurons are glutamatergic and can drive the activity of the lateral habenula, which, in turn, provides an indirect inhibitory influence on midbrain dopamine neurons. We show that GPh neurons receive inhibitory input from the striosomal compartment of the striatum. The striosomal input can reduce the excitatory drive to the lateral habenula and, consequently, decrease the inhibition onto the dopaminergic system. Dopaminergic neurons, in turn, provide feedback that inhibits the GPh. In addition, GPh neurons receive direct projections from the pallium (cortex in mammals), which can increase the GPh activity to drive the lateral habenula to increase the inhibition of the neuromodulatory systems. This circuitry, thus, differs markedly from the “direct” and “indirect” pathways that regulate the pallidal (e.g., globus pallidus) output nuclei involved in the control of motion. Our results show that a distinct reward–evaluation circuit exists within the basal ganglia, in parallel to the direct and indirect pathways, which select actions. Our results suggest that these circuits are part of the fundamental blueprint that all vertebrates use to select actions and evaluate their outcome. PMID:24003130

  1. TNF? levels and macrophages expression reflect an inflammatory potential of trigeminal ganglia in a mouse model of familial hemiplegic migraine.

    PubMed

    Franceschini, Alessia; Vilotti, Sandra; Ferrari, Michel D; van den Maagdenberg, Arn M J M; Nistri, Andrea; Fabbretti, Elsa

    2013-01-01

    Latent changes in trigeminal ganglion structure and function resembling inflammatory conditions may predispose to acute attacks of migraine pain. Here, we investigated whether, in trigeminal sensory ganglia, cytokines such as TNF? might contribute to a local inflammatory phenotype of a transgenic knock-in (KI) mouse model of familial hemiplegic migraine type-1 (FHM-1). To this end, macrophage occurrence and cytokine expression in trigeminal ganglia were compared between wild type (WT) and R192Q mutant Ca(V)2.1 Ca(2+) channel (R192Q KI) mice, a genetic model of FHM-1. Cellular and molecular characterization was performed using a combination of confocal immunohistochemistry and cytokine assays. With respect to WT, R192Q KI trigeminal ganglia were enriched in activated macrophages as suggested by their morphology and immunoreactivity to the markers Iba1, CD11b, and ED1. R192Q KI trigeminal ganglia constitutively expressed higher mRNA levels of IL1?, IL6, IL10 and TNF? cytokines and the MCP-1 chemokine. Consistent with the report that TNF? is a major factor to sensitize trigeminal ganglia, we observed that, following an inflammatory reaction evoked by LPS injection, TNF? expression and macrophage occurrence were significantly higher in R192Q KI ganglia with respect to WT ganglia. Our data suggest that, in KI trigeminal ganglia, the complex cellular and molecular environment could support a new tissue phenotype compatible with a neuroinflammatory profile. We propose that, in FHM patients, this condition might contribute to trigeminal pain pathophysiology through release of soluble mediators, including TNF?, that may modulate the crosstalk between sensory neurons and resident glia, underlying the process of neuronal sensitisation. PMID:23326332

  2. Developmental analysis reveals labial and subradular ganglia and the primary framework of the nervous system in nudibranch gastropods.

    PubMed

    Page, L R

    1993-11-01

    Previous ultrastructural observations on late stage larvae of dorid nudibranchs (Gastropoda, Opisthobranchia) revealed two pairs of ganglia within the base of the foot that do not have obvious counterparts in existing descriptions of other gastropod larvae [Chia and Koss (1989). Cell Tiss. Res. 256:17-26.] One of these ganglionic pairs has been implicated in the initiation of settlement preceding metamorphosis [Arkett et al. (1989). Biol. Bull. 176:155-160.] By examining neurogenesis in sequential larval stages, I have found that the pattern of connectives and commissures associated with these enigmatic ganglia is comparable to patterns found in less consolidated adult nervous systems of chitons, monoplacophorans, and archaeogastropods. These comparative data suggest that the two pairs of ganglia in dorid nudibranch larvae are homologues of labial and subradular ganglia. The labial ganglia become incorporated into the cerebral ganglia at metamorphosis. In an attempt to integrate anatomical and developmental observations with behavioral and neurophysiological results, I suggest that receptor cells of the larval labial ganglia may become postmetamorphic primary mechanoreceptors of the oral tube, which have central cell bodies within the "cerebral" ganglia and which help coordinate feeding. Results of this study also address a larger evolutionary issue by questioning the traditional model of an ancestral molluscan nervous system that consists of four longitudinal nerve cords that arise from separate sites along a circumesophageal nerve ring. This pattern results from secondary connections in nudibranchs and possibly other molluscs. The primary condition of a single axon bundle emerging from each cerebral ganglion is more similar to the developing nervous system in polychaete annelids than what has been recognized previously. PMID:8283184

  3. BLOOD VESSELS IN GANGLIA IN HUMAN ESOPHAGUS MIGHT EXPLAIN THE HIGHER FREQUENCY OF MEGAESOPHAGUS COMPARED WITH MEGACOLON

    PubMed Central

    Adad, Sheila Jorge; Etchebehere, Renata Margarida; Jammal, Alessandro Adad

    2014-01-01

    This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon. PMID:25351549

  4. Widespread abnormality of the ?-aminobutyric acid-ergic system in Tourette syndrome

    PubMed Central

    Bagic, Anto; Simmons, Janine M.; Mari, Zoltan; Bonne, Omer; Xu, Ben; Kazuba, Diane; Herscovitch, Peter; Carson, Richard E.; Murphy, Dennis L.; Drevets, Wayne C.; Hallett, Mark

    2012-01-01

    Dysfunction of the ?-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive–compulsive disorder. The purpose of this study was to identify a possible dysfunction of the ?-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20?mCi of [11C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABAA receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABAA receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABAA receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics. PMID:22577221

  5. Abnormalities of the Optic Fundus

    PubMed Central

    Tannenbaum, David W.; Mandelcorn, Mark S.

    1990-01-01

    Common abnormalities of the optic fundus are illustrated in this article. The authors provide brief clinical descriptions and discuss a test used to screen for a shallow anterior chamber of the eye before dilating the pupil. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16Figure 17 PMID:21234023

  6. Mitochondrial abnormalities in Alzheimer's disease.

    PubMed

    Hirai, K; Aliev, G; Nunomura, A; Fujioka, H; Russell, R L; Atwood, C S; Johnson, A B; Kress, Y; Vinters, H V; Tabaton, M; Shimohama, S; Cash, A D; Siedlak, S L; Harris, P L; Jones, P K; Petersen, R B; Perry, G; Smith, M A

    2001-05-01

    The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease. PMID:11312286

  7. Deregulation of mitochondria-shaping proteins Opa-1 and Drp-1 in manganese-induced apoptosis.

    PubMed

    Alaimo, Agustina; Gorojod, Roxana M; Beauquis, Juan; Muñoz, Manuel J; Saravia, Flavia; Kotler, Mónica L

    2014-01-01

    Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may provide new therapeutic tools for the treatment of Manganism and other neurodegenerative diseases. PMID:24632637

  8. Deregulation of Mitochondria-Shaping Proteins Opa-1 and Drp-1 in Manganese-Induced Apoptosis

    PubMed Central

    Alaimo, Agustina; Gorojod, Roxana M.; Beauquis, Juan; Muñoz, Manuel J.; Saravia, Flavia; Kotler, Mónica L.

    2014-01-01

    Mitochondria are dynamic organelles that undergo fusion and fission processes. These events are regulated by mitochondria-shaping proteins. Changes in the expression and/or localization of these proteins lead to a mitochondrial dynamics impairment and may promote apoptosis. Increasing evidence correlates the mitochondrial dynamics disruption with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia where mitochondria from astrocytes represent an early target. Using MitoTracker Red staining we observed increased mitochondrial network fission in Mn-exposed rat astrocytoma C6 cells. Moreover, Mn induced a marked decrease in fusion protein Opa-1 levels as well as a dramatic increase in the expression of fission protein Drp-1. Additionally, Mn provoked a significant release of high MW Opa-1 isoforms from the mitochondria to the cytosol as well as an increased Drp-1 translocation to the mitochondria. Both Mdivi-1, a pharmacological Drp-1 inhibitor, and rat Drp-1 siRNA reduced the number of apoptotic nuclei, preserved the mitochondrial network integrity and prevented cell death. CsA, an MPTP opening inhibitor, prevented mitochondrial Δψm disruption, Opa-1 processing and Drp-1 translocation to the mitochondria therefore protecting Mn-exposed cells from mitochondrial disruption and apoptosis. The histological analysis and Hoechst 33258 staining of brain sections of Mn-injected rats in the striatum showed a decrease in cellular mass paralleled with an increase in the occurrence of apoptotic nuclei. Opa-1 and Drp-1 expression levels were also changed by Mn-treatment. Our results demonstrate for the first time that abnormal mitochondrial dynamics is implicated in both in vitro and in vivo Mn toxicity. In addition we show that the imbalance in fusion/fission equilibrium might be involved in Mn-induced apoptosis. This knowledge may provide new therapeutic tools for the treatment of Manganism and other neurodegenerative diseases. PMID:24632637

  9. Structural brain abnormalities in cervical dystonia

    PubMed Central

    2013-01-01

    Background Idiopathic cervical dystonia is characterized by involuntary spasms, tremors or jerks. It is not restricted to a disturbance in the basal ganglia system because non-conventional voxel-based MRI morphometry (VBM) and diffusion tensor imaging (DTI) have detected numerous regional changes in the brains of patients. In this study scans of 24 patients with cervical dystonia and 24 age-and sex-matched controls were analysed using VBM, DTI and magnetization transfer imaging (MTI) using a voxel-based approach and a region-of-interest analysis. Results were correlated with UDRS, TWSTRS and disease duration. Results We found structural alterations in the basal ganglia; thalamus; motor cortex; premotor cortex; frontal, temporal and parietal cortices; visual system; cerebellum and brainstem of the patients with dystonia. Conclusions Cervical dystonia is a multisystem disease involving several networks such as the motor, sensory and visual systems. PMID:24131497

  10. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography

    SciTech Connect

    Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.

    1985-05-01

    Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities.

  11. Morphology and physiology of vibratory interneurons in the thoracic ganglia of the southern green stinkbug Nezara viridula (L.).

    PubMed

    Zorovi?, Maja; Presern, Janez; Cokl, Andrej

    2008-05-10

    The central processing mechanisms of vibratory signals in small plant-dwelling insects that rely primarily on substrate-borne vibratory communication are still largely unknown. To elucidate the neural mechanisms involved in vibratory signaling, the vibration-sensitive interneurons in thoracic ganglia of the southern green stinkbug, Nezara viridula, were investigated electrophysiologically by single-cell recordings and staining. Ten types of interneurons were described and divided into four categories, based on their gross morphology. The cell body of the L-shaped CG-AC neurons is located in the metathoracic neuromere of the central ganglion, and the axon ascends contralaterally. This group comprises five types of neurons differing in their fine structure and functional properties. CG-AB neurons are dorsal unpaired median (DUM) neurons with cell bodies in the mesothoracic neuromere of the central ganglion and two axons that ascend bilaterally into the prothoracic ganglion. Group CG-L includes three types of local neurons limited to the central ganglion. With ipsilateral dendritic arborizations and contralateral axonal branching, their gross morphology is similar to that of cricket omega cells. Interneuron PTG-DC, with the cell body in the prothoracic ganglion (PTG) and a contralaterally descending axon, conveys information received by the sensory organs of the front contralateral leg to the neuropil regions of the ipsilateral middle and hind legs. Based on their frequency tuning and acceleration sensitivity, the vibratory interneurons fall into two groups: the low-frequency units are tuned to 50 Hz and the middle frequency units to 200 Hz, with their acceleration thresholds at 10(-1) m/s(2) and 5 x 10(-3) m/s(2), respectively. Their function is discussed with relevance to the vibratory communication of N. viridula. PMID:18335563

  12. Abnormal circling behavior in rat mutants and its relevance to model specific brain dysfunctions.

    PubMed

    Löscher, Wolfgang

    2010-01-01

    Circling or rotational behavior is the most studied indicator of cerebral asymmetry in the rat. In humans, disturbances in cerebral asymmetry are involved in the etiology of several psychiatric disorders, including schizophrenia, Tourette syndrome and attention-deficit hyperactivity disorder. Abnormal rotational behavior in rodents is indicative of either an imbalance of forebrain dopamine systems, particularly an imbalance of nigrostriatal function, or an inner ear disease affecting the vestibular (balance) system. Abnormally enhanced circling behavior has been described in several mutant rat and mouse strains both with and without defects of the vestibular system. However, the relationship between vestibular defects and lateralized circling in rodents is only incompletely understood. In this review, we describe and discuss various spontaneous mutations associated with abnormal circling behavior in different rat strains and their potential relevance to model specific brain dysfunctions. The circling rat mutants described in this review illustrate how genetic animal models may serve to study multifaceted brain functions and dysfunctions, including disorders of the basal ganglia and vestibular system. PMID:19607857

  13. Abnormal eye movements in blepharospasm and involuntary levator palpebrae inhibition. Clinical and pathophysiological considerations.

    PubMed

    Aramideh, M; Bour, L J; Koelman, J H; Speelman, J D; Ongerboer de Visser, B W

    1994-12-01

    We report on four patients with involuntary eyelid closure and eye movement disorders. Three were healthy until the onset of their illness and one had a mild generalized choreoathetosis and dystonia due to kernicterus. Electromyographic recording revealed solely blepharospasm in two patients and blepharospasm in combination with involuntary levator palpebrae inhibition in the other two. The eye movement abnormalities were clinically characterized by inability to fix gaze and short or prolonged episodes of uncontrollable eye deviations accompanied, in two patients, by diplopia in horizontal or vertical directions. These episodes occurred independently of a disorder of eyelid movement. Eye movement recordings with a double magnetic induction technique showed saccadic intrusions in horizontal directions. They consisted of highly frequent square wave jerks in three and sporadic macro-square wave jerks in two patients. There were also episodes of extraocular muscle dystonia, commonly known as oculogyric crises, resulting in involuntary upward eye deviation in all patients and lateral deviation in three patients. In one patient, nasal-ward deviations were sometimes restricted to one eye. We conclude that these abnormal eye movements do not necessarily point to a symptomatic form of dystonia and that they may limit the beneficial effect of botulinum toxin or surgical intervention in the therapeutic management of involuntary eyelid closure. We suggest that either basal ganglia, especially substantia nigra pars reticularis and the brainstem structures, especially the paramedian pontine reticular formation, or both, may be involved in the pathogenesis of these abnormal movements. PMID:7820580

  14. Comprehensive in vivo mapping of the human basal ganglia and thalamic connectome in individuals using 7T MRI.

    PubMed

    Lenglet, Christophe; Abosch, Aviva; Yacoub, Essa; De Martino, Federico; Sapiro, Guillermo; Harel, Noam

    2012-01-01

    Basal ganglia circuits are affected in neurological disorders such as Parkinson's disease (PD), essential tremor, dystonia and Tourette syndrome. Understanding the structural and functional connectivity of these circuits is critical for elucidating the mechanisms of the movement and neuropsychiatric disorders, and is vital for developing new therapeutic strategies such as deep brain stimulation (DBS). Knowledge about the connectivity of the human basal ganglia and thalamus has rapidly evolved over recent years through non-invasive imaging techniques, but has remained incomplete because of insufficient resolution and sensitivity of these techniques. Here, we present an imaging and computational protocol designed to generate a comprehensive in vivo and subject-specific, three-dimensional model of the structure and connections of the human basal ganglia. High-resolution structural and functional magnetic resonance images were acquired with a 7-Tesla magnet. Capitalizing on the enhanced signal-to-noise ratio (SNR) and enriched contrast obtained at high-field MRI, detailed structural and connectivity representations of the human basal ganglia and thalamus were achieved. This unique combination of multiple imaging modalities enabled the in-vivo visualization of the individual human basal ganglia and thalamic nuclei, the reconstruction of seven white-matter pathways and their connectivity probability that, to date, have only been reported in animal studies, histologically, or group-averaged MRI population studies. Also described are subject-specific parcellations of the basal ganglia and thalamus into sub-territories based on their distinct connectivity patterns. These anatomical connectivity findings are supported by functional connectivity data derived from resting-state functional MRI (R-fMRI). This work demonstrates new capabilities for studying basal ganglia circuitry, and opens new avenues of investigation into the movement and neuropsychiatric disorders, in individual human subjects. PMID:22235267

  15. Abnormal Striatal Dopaminergic Neurotransmission during Rest and Task Production in Spasmodic Dysphonia

    PubMed Central

    Berman, Brian D.; Herscovitch, Peter; Hallett, Mark

    2013-01-01

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia–thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [11C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ?BP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ?BP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ?BP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ?BP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder. PMID:24027271

  16. How to Interpret Abnormal Pap Smear Results

    MedlinePLUS

    ... Cervical Cancer | How to Interpret Abnormal Pap Smear Results What does an abnormal Pap smear mean? A ... are located in your cervix or uterus. These results mean that some of your glandular cells are ...

  17. Cardiac abnormalities in birth asphyxia.

    PubMed

    Ranjit, M S

    2000-03-01

    Cardiac abnormalities in birth asphyxia were first recognised in 1970s. These include (i) transient tricuspid regurgitation which is the commonest cause of a systolic murmur in a newborn and tends to disappear without any treatment unless it is associated with transient myocardial ischemia or primary pulmonary hypertension of the new born (ii) transient mitral regurgitation which is much less common and is often a part of transient myocardial ischemia, at times with reduced left ventricular function and therefore, requires treatment in the form of inotropic and ventilatory support, (iii) transient myocardial ischemia (TMI) of the newborn. This should be suspected in any baby with asphyxia, respiratory distress and poor pulses especially if a murmur is audible. It is of five types (A to E) according to Rowe's classification. Type B is the most severe with respiratory distress, congestive heart failure and shock. Echocardiography helps to rule out critical left ventricular obstructive lesions like hypoplastic left heart syndrome or critical aortic stenosis. ECG is very important for diagnosis of TMI, and may show changes ranging from T wave inversion in one lead to a classical segmental infarction pattern with abnormal q waves. CPK-MB may rise and echocardiogram shows impaired left ventricular function, mitral and/or tricuspid regurgitation, and at times, wall motion abnormalities of left ventricle. Ejection fraction is often depressed and is a useful marker of severity and prognosis. Treatment includes fluid restriction, inotropic support, diuretics and ventilatory resistance if required, (v) persistent pulmonary hypertension of the new born (PPHN). Persistent hypoxia sometimes results in persistence of constricted fetal pulmonary vascular bed causing pulmonary arterial hypertension with consequent right to left shunt across patent ductus arteriosus and foramen ovale. This causes respiratory distress and cyanosis (sometimes differential). Clinical examination also reveals evidence of pulmonary arterial hypertension and right ventricular failure with systolic murmur of tricuspid and, at times, mitral regurgitation. Treatment consists of oxygen and general care for mild cases, ventilatory support, ECMO and nitric oxide for severe cases. Cardiac abnormalities in asphyxiated neonates are often underdiagnosed and require a high index of suspicion. ECG and Echo help in early recognition and hence better management of these cases. PMID:11129917

  18. Cardiac abnormalities in birth asphyxia.

    PubMed

    Ranjit, M S

    2000-07-01

    Cardiac abnormalities in birth asphyxia were first recognised in the 1970s. These include (i) transient tricuspid regurgitation which is the commonest cause of a systolic murmur in a newborn and tends to disappear without any treatment unless it is associated with transient myocardial ischemia or primary pulmonary hypertension of the newborn (ii) transient mitral regurgitation which is much less common and is often a part of transient myocardial ischemia, at times with reduced left ventricular function and, therefore, requires treatment in the form of inotropic and ventilatory support (iii) transient myocardial ischemia (TMI) of the newborn. This should be suspected in any baby with asphyxia, respiratory distress and poor pulses, especially if a murmur is audible. It is of five types (A to E) according to Rowe's classification. Type B is the most severe with respiratory distress, congestive heart failure and shock. Echocardiography helps to rule out critical left ventricular obstructive lesions like hypoplastic left heart syndrome or critical aortic stenosis. ECG is very important for diagnosis of TMI, and may show changes ranging from T wave inversion in one lead to a classical segmental infarction pattern with abnormal q waves. CPK-MB may rise and echocardiogram shows impaired left ventricular function, mitral and/or tricuspid regurgitation, and at times, wall motion abnormalities of left ventricle. Ejection fraction is often depressed and is a useful marker of severity and prognosis. Treatment includes fluid restriction, inotropic support, diuretics and ventilatory resistance if required (v) persistent pulmonary hypertension of the newborn (PPHN). Persistent hypoxia sometimes results in persistence of constricted fetal pulmonary vascular bed causing pulmonary arterial hypertension with consequent right to left shunt across patent ductus arteriosus and foramen ovale. This causes respiratory tension and right ventricular failure with systolic murmur of tricuspid, and at times, mitral regurgitation. Treatment consists of oxygen and general care for mild cases, ventilatory support, ECMO and nitric oxide for severe cases. Cardiac abnormalities in asphyxiated neonates are often underdiagnosed and require a high index of suspicion. ECG and Echo help in early recognition and hence better management of these cases. PMID:10957839

  19. Foot abnormalities of wild birds

    USGS Publications Warehouse

    Herman, C.M.; Locke, L.N.; Clark, G.M.

    1962-01-01

    The various foot abnormalities that occur in birds, including pox, scaly-leg, bumble-foot, ergotism and freezing are reviewed. In addition, our findings at the Patuxent Wildlife Research Center include pox from dove, mockingbird, cowbird, grackle and several species of sparrows. Scaly-leg has been particularly prevalent on icterids. Bumble foot has been observed in a whistling swan and in a group of captive woodcock. Ergotism is reported from a series of captive Canada geese from North Dakota. Several drug treatments recommended by others are presented.

  20. Development of nNOS-positive neurons in the rat sensory ganglia after capsaicin treatment.

    PubMed

    Masliukov, Petr M; Moiseev, Konstantin Y; Korzina, Marina B; Porseva, Valentina V

    2015-08-27

    To gain a better understanding of the neuroplasticity of afferent neurons during postnatal ontogenesis, the distribution of neuronal nitric oxide synthase (nNOS) immunoreactivity was studied in the nodose ganglion (NG) and Th2 and L4 dorsal root ganglia (DRG) from vehicle-treated and capsaicin-treated female Wistar rats at different ages (10-day-old, 20-day-old, 30-day-old, and two-month-old). The percentage of nNOS-immunoreactive (IR) neurons decreased after capsaicin treatment in all studied ganglia in first 20 days of life, from 55.4% to 36.9% in the Th2 DRG, from 54.6% to 26.1% in the L4 DRG and from 37.1% to 15.0% in the NG. However, in the NG, the proportion of nNOS-IR neurons increased after day 20, from 11.8% to 23.9%. In the sensory ganglia of all studied rats, a high proportion of nNOS-IR neurons bound isolectin B4. Approximately 90% of the sensory nNOS-IR neurons bound to IB4 in the DRG and approximately 80% in the NG in capsaicin-treated and vehicle-treated rats. In 10-day-old rats, a large number of nNOS-IR neurons also expressed TrkA, and the proportion of nNOS(+)/TrkA(+) neurons was larger in the capsaicin-treated rats compared with the vehicle-treated animals. During development, the percentage of nNOS(+)/TrkA(+) cells decreased in the first month of life in both groups. The information provided here will also serve as a basis for future studies investigating mechanisms of sensory neuron development. PMID:26054303

  1. Processing of temporal information and the basal ganglia: new evidence from fMRI.

    PubMed

    Nenadic, Igor; Gaser, Christian; Volz, Hans-Peter; Rammsayer, Thomas; Häger, Frank; Sauer, Heinrich

    2003-01-01

    Temporal information processing is a fundamental brain function, which might include central timekeeping mechanisms independent of sensory modality. Psychopharmacological and patient studies suggest a crucial role of the basal ganglia in time estimation. In this study, functional magnetic resonance imaging (fMRI) was applied in 15 healthy right-handed male subjects performing an auditory time estimation task (duration discrimination of tone pairs in the range of 1,000-1,400 ms) and frequency discriminations (tone pairs differing in pitch, around 1,000 Hz) as an active control task. Task difficulty was constantly modulated by an adaptive algorithm (weighted up-down method) reacting on individual performance. Time estimation (vs rest condition) elicited a distinct pattern of cerebral activity, including the right medial and both left and right dorsolateral prefrontal cortices (DLPFC), thalamus, basal ganglia (caudate nucleus and putamen), left anterior cingulate cortex, and superior temporal auditory areas. Most activations showed lateralisation to the right hemisphere and were similar in the frequency discrimination task. Comparing time and frequency tasks, we isolated activation in the right putamen restricted to time estimation only. This result supports the notion of central processing of temporal information associated with basal ganglia activity. Temporal information processing in the brain might thus be a distributed process of interaction between modality-dependent sensory cortical function, the putamen (with a timing-specific function), and additional prefrontal cortical systems related to attention and memory. Further investigations are needed to delineate the differential contributions of the striatum and other areas to timing. PMID:12520413

  2. Association between a Novel Mutation in SLC20A2 and Familial Idiopathic Basal Ganglia Calcification

    PubMed Central

    Zhang, Yang; Guo, Xianan; Wu, Anhua

    2013-01-01

    Familial idiopathic basal ganglia calcification (FIBGC) is a rare, autosomal dominant disorder involving bilateral calcification of the basal ganglia. To identify gene mutations related to a Chinese FIBGC lineage, we evaluated available individuals in the family using CT scans. DNA was extracted from the peripheral blood of available family members, and both exonic and flanking intronic sequences of the SLC20A2 gene were amplified by PCR and then sequenced. Non-denaturing polyacrylamide gel electrophoresis (PAGE) was used to confirm the presence of mutations. Allele imbalances of the SLC20A2 gene or relative quantity of SLC20A2 transcripts were evaluated using qRT-PCR. A novel heterozygous single base-pair deletion (c.510delA) within the SLC20A2 gene was identified. This deletion mutation was found to co-segregate with basal ganglia calcification in all of the affected family members but was not detected in unaffected individuals or in 167 unrelated Han Chinese controls. The mutation will cause a frameshift, producing a truncated SLC20A2 protein with a premature termination codon, most likely leading to the complete loss of function of the SLC20A2 protein. This mutation may also lead to a reduction in SLC20A2 mRNA expression by approximately 30% in cells from affected individuals. In conclusion, we identified a novel mutation in SLC20A2 that is linked to FIBGC. In addition to the loss of function at the protein level, decreasing the expression of SLC20A2 mRNA may be another mechanism that can regulate SLC20A2 function in IBGC individuals. We propose that the regional expression pattern of SLC20A1 and SLC20A2 might explain the unique calcification pattern observed in FIBGC patients. PMID:23437308

  3. Prediction of the Location of the Pyramidal Tract in Patients with Thalamic or Basal Ganglia Tumors

    PubMed Central

    Xu, BaiNan

    2012-01-01

    Background Locating the pyramidal tract (PT) is difficult in patients with thalamic or basal ganglia tumors, especially when the surrounding anatomical structures cannot be identified using computed tomography or magnetic resonance images. Hence, we objected to find a way to predict the location of the PT in patients with thalamic and basal ganglia tumors Methodology/Principal Findings In 59 patents with thalamic or basal ganglia tumors, the PTs were constructed by with diffusion tensor imaging (DTI)-based fiber tracking (FT). In axial slices crossing the foramen of Monro, the tumor position was classified according to three lines. Line 1 was vertical and crossed the vertex point of the anterior limbs of the internal capsule. Lines 2 and line 3 were horizontal and crossed the foramen of Monro and joint of the middle and lateral thirds of the posterior limbs, respectively. Six (10.17%) patients were diagnosed with type 1 tumor, six (10.17%) with type 2, seven (11.86%) with type 3a, five (8.47%) with type 3b, 17 (28.81%) with type 4a, six (10.17%) with type 4b, three (5.08%) with type 5, and nine (15.25%) with type 6. In type 1 tumors, the PTs were located at the 12 o'clock position of the tumor, type 2 at six o'clock, type 3a between nine and 12 o'clock, type 3 between six and nine o'clock, type 4a between 12 and three o'clock, type 4b at three o'clock, type 5 between six and nine o'clock, and type 6 between three and six o'clock. Conclusions/Significance The position of the PT relative to the tumor could be determined according to the tumor location. These results could prove helpful in determining the location of the PT preoperatively. PMID:23155395

  4. Increased volume and impaired function: the role of the basal ganglia in writer’s cramp

    PubMed Central

    Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Hefter, Harald; Hallett, Mark; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten

    2015-01-01

    Introduction The pathophysiology of writer's cramp, a task-specific dystonia, remains unclear. The objective of this study was to investigate the basal ganglia circuit and the cerebellum during a complex motor sequence learning task carried out with the nonaffected hand in writer's cramp patients. Methods We applied structural and functional imaging in 22 writer's cramp patients and 28 matched controls using 3T MRI. With the asymptomatic left hand all participants learned a complex, sequential, five-element sequence-tapping task as accurately and quickly as possible. Functional imaging was measured during a repeated (15 times), fixed block design with tapping (30 sec) and rest (30 sec). Additionally, gray matter volume of the basal ganglia was analyzed using voxel-based morphometry (VBM). Results While behavior was comparable between groups, after small volume correction the anterior part of the right putamen and the left globus pallidus exhibited reduced blood oxygen level-dependent (BOLD) activity in patients during the sequential finger-tapping task. VBM analysis showed larger gray matter volume bilateral in the posterior part of the putamen and globus pallidus. There were no group differences in the cerebellum. Conclusion The results indicate an impairment of anterior basal ganglia loops involved in producing complex sequential movements of the unaffected hand. These findings are in line with previous reports of reduced neuronal activity in the globus pallidus internus. Higher gray matter volume of the putamen and globus pallidus may stem from elevated activity of the direct pathway, which could reflect a compensatory phenomenon or a primary predisposition, that is, endophenotypic trait. PMID:25642386

  5. Depolarizing actions of ?-aminobutyric acid and related compounds on rat superior cervical ganglia in vitro

    PubMed Central

    Bowery, N.G.; Brown, D.A.

    1974-01-01

    1 Potential changes in rat superior cervical ganglia were recorded in vitro with surface electrodes. 2 ?-aminobutyric acid (GABA) produced a transient, low-amplitude ganglion depolarization at rest, and a transient hyperpolarization in ganglia depolarized by carbachol. Depolarization was not prevented by preganglionic denervation. The log dose-response curve for depolarization was sigmoid with a mean ED50 of 12.5 ?M. 3 The ganglion was depolarized in similar manner by the following compounds (mean molar potencies relative to GABA (=1) in brackets): 3-aminopropane sulphonic acid (3.4), ?-amino-?-hydroxybutyric acid (0.27), ?-guanidino-propionic acid (0.12), guanidinoacetic acid (0.057), ?-aminovaleric acid (0.048), ?-alanine (0.01), 2,4-diaminobutyric acid, ?-guanidinobutyric acid, taurine and N-methyl-GABA (all <0.01). The following compounds did not depolarize the ganglion at 10 mM concentrations: ?- and ?-amino-n-butyric acids, ?-amino-iso-butyric acid, glycine and glutamic acid. 4 Depolarization declined in the continued presence of GABA. Ganglia thus `desensitized' to GABA showed a diminished response to other amino acids but not to carbachol. 5 The effect of GABA was not antagonized by hyoscine and hexamethonium in combination, in concentrations sufficient to block responses to carbachol. 6 Responses to GABA were blocked more readily than those to carbachol by bicuculline (IC50, 14 ?M) and picrotoxin (IC50, 37 ?M). Strychnine (IC50, 73 ?M) was a relatively weak and less selective GABA-antagonist. 7 It is concluded that sympathetic ganglion cells possess receptors for GABA and related amino acids which are (a) different from the acetylcholine receptors and (b) similar to GABA receptors in the central nervous system. PMID:4154116

  6. Prox1 identifies proliferating neuroblasts and nascent neurons during neurogenesis in sympathetic ganglia.

    PubMed

    Holzmann, Julia; Hennchen, Melanie; Rohrer, Hermann

    2015-12-01

    Neurogenesis in embryonic sympathetic ganglia involves neuroblasts that resume proliferation following neuronal differentiation. As cell cycle exit is not associated with neuronal differentiation, the identity of proliferating neuroblasts is incompletely understood. Here, we use sympathetic ganglia of chick embryos to define the timing of neurogenesis and neuroblast identity focusing on the expression and function of the transcription factor Prox1. We show that a large fraction of neuroblasts has initially withdrawn from the cell cycle at embryonic day 3 (E3), which is reflected by a high proportion of p27(+) /Islet1(+) neuroblasts (63%) and low numbers of EdU(+) /Islet1(+) cells (12%). The proportion of proliferating Islet1(+) neuroblasts, identified by EdU pulse labeling and by the absence of the postmitotic marker p27 increases to reach maximal levels at E5, when virtually all neuroblasts are in the cell cycle (95%). Subsequently, the proportion of EdU-labeled and p27(-) neuroblasts is reduced to reach low levels at E11. Interestingly, the expression of the transcription factor Prox1 is restricted to the neuronal lineage, that is, Sox10(+) /Phox2b(+) neuron progenitors, proliferating p27(-) /Islet1(+) neuroblasts and nascent neurons but is rapidly lost in postmitotic neurons. In vitro and in vivo knockdown and overexpression experiments demonstrate effects of Prox1 in the support of neuroblast proliferation and survival. Taken together, these results define the neurogenesis period in the chick paravertebral sympathetic ganglia including an initial cell cycle withdrawal and identify Prox1 as a marker and regulator of proliferating sympathetic neuroblasts. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1352-1367, 2015. PMID:25788138

  7. Association between a novel mutation in SLC20A2 and familial idiopathic basal ganglia calcification.

    PubMed

    Zhang, Yang; Guo, Xianan; Wu, Anhua

    2013-01-01

    Familial idiopathic basal ganglia calcification (FIBGC) is a rare, autosomal dominant disorder involving bilateral calcification of the basal ganglia. To identify gene mutations related to a Chinese FIBGC lineage, we evaluated available individuals in the family using CT scans. DNA was extracted from the peripheral blood of available family members, and both exonic and flanking intronic sequences of the SLC20A2 gene were amplified by PCR and then sequenced. Non-denaturing polyacrylamide gel electrophoresis (PAGE) was used to confirm the presence of mutations. Allele imbalances of the SLC20A2 gene or relative quantity of SLC20A2 transcripts were evaluated using qRT-PCR. A novel heterozygous single base-pair deletion (c.510delA) within the SLC20A2 gene was identified. This deletion mutation was found to co-segregate with basal ganglia calcification in all of the affected family members but was not detected in unaffected individuals or in 167 unrelated Han Chinese controls. The mutation will cause a frameshift, producing a truncated SLC20A2 protein with a premature termination codon, most likely leading to the complete loss of function of the SLC20A2 protein. This mutation may also lead to a reduction in SLC20A2 mRNA expression by approximately 30% in cells from affected individuals. In conclusion, we identified a novel mutation in SLC20A2 that is linked to FIBGC. In addition to the loss of function at the protein level, decreasing the expression of SLC20A2 mRNA may be another mechanism that can regulate SLC20A2 function in IBGC individuals. We propose that the regional expression pattern of SLC20A1 and SLC20A2 might explain the unique calcification pattern observed in FIBGC patients. PMID:23437308

  8. The basal ganglia in perceptual timing: timing performance in Multiple System Atrophy and Huntington's disease.

    PubMed

    Cope, Thomas E; Grube, Manon; Singh, Baldev; Burn, David J; Griffiths, Timothy D

    2014-01-01

    The timing of perceptual events depends on an anatomically and functionally connected network comprising basal ganglia, cerebellum, pre-frontal cortex and supplementary motor area. Recent studies demonstrate the cerebellum to be involved in absolute, duration-based timing, but not in relative timing based on a regular beat. Conversely, functional involvement of the striatum is observed in relative timing, but its role in absolute timing is unclear. This work tests the specific role of the basal ganglia in the perceptual timing of auditory events. It aims to distinguish the hypothesised unified model of time perception (Teki, Grube, & Griffiths, 2012), in which the striatum is a mandatory component for all timing tasks, from a modular system in which they subserve relative timing, with absolute timing processed by the cerebellum. Test groups comprised individuals with Multiple System Atrophy, a disorder in which similar pathology can produce clinical deficits associated with dysfunction of the cerebellum (MSA-C, n = 8) or striatum (MSA-P, n = 10), and early symptomatic Huntington's disease (HD, n = 14). Individuals with chronic autoimmune peripheral neuropathy (n = 11) acted as controls. Six adaptive tasks were carried out to assess perceptual thresholds for absolute timing through duration discrimination for sub- and supra-second time intervals, and relative timing through the detection of beat-based regularity and irregularity, detection of a delay within an isochronous sequence, and the discrimination of sequences with metrical structure. All three patient groups exhibited impairments in performance in comparison with the control group for all tasks, and severity of impairment was significantly correlated with disease progression. No differences were demonstrated between MSA-C and MSA-P, and the most severe impairments were observed in those with HD. The data support an obligatory role for the basal ganglia in all tested timing tasks, both absolute and relative, as predicted by the unified model. The results are not compatible with models of a brain timing network based upon independent modules. PMID:24135486

  9. Task-set switching deficits in early-stage Huntington's disease: implications for basal ganglia function.

    PubMed

    Aron, Adam R; Watkins, Laura; Sahakian, Barbara J; Monsell, Stephen; Barker, Roger A; Robbins, Trevor W

    2003-07-01

    Executive functions are likely mediated by interconnected circuits including frontal lobe and basal ganglia structures. We assessed the executive function of task switching in patients with early-stage Huntington's disease (HD), a neurodegenerative disease affecting the basal ganglia. In two experiments, the HD patients had greater difficulty when switching than when repeating a task than matched controls, and this was true even when scaling for the overall slowing of the patients. In the first experiment, HD patients had a switching deficit even in a "pure" condition where they had to switch, predictably, and with substantial preparation time, between stimuli having only one possible response, indicating a switching deficit different from that for patients with Parkinson's disease or frontal lobe trauma, and possibly relating to inadequate activation of stimulus-response links or "response set." In the more elaborate second experiment, we could not account for the switching deficit of the patients in terms of inadequate preparation in advance of a switch, deficient suppression of task-set processing from the preswitch trial, or impaired suppression of interference due to the presence of a competing task set. Instead, we found that part of the switching deficit was due to elevated reaction time and errors on switch trials for a repeated response (same button press as on preswitch trial) relative to an alternated response (different button press from preswitch trial). We argue that this elevated "repetition effect" for the HD patients is due to excessive inhibition of the just-performed response in advance of a switch. Alterations in the "response-setting" process alone (Experiment 1) and both the response-setting and "response inhibition" process (Experiment 2) probably arise from striatal pathology in HD, thus accounting for the task-switching deficits and showing how basal ganglia implemented response processes may underpin executive function. PMID:12965037

  10. The formation of synapses in mammalian sympathetic ganglia reinnervated with preganglionic or somatic nerves

    PubMed Central

    McLachlan, Elspeth M.

    1974-01-01

    1. A study has been made of the formation of synapses in the superior cervical ganglion of the guinea-pig, during reinnervation either with axons of the cervical sympathetic trunk, or with somatic axons of the nerve to the sternohyoid muscle. 2. No significant changes in either the geometry or electrical parameters of sympathetic motorneurones were detected following denervation for periods of 3-6 weeks, or after reinnervation with either preganglionic or somatic axons. 3. The post-ganglionic action potential reappeared about 4 weeks after preganglionic trunk section (eighteen of eighteen ganglia); its amplitude increased progressively and was almost normal by more than 10 weeks after nerve section. A very small response was detected from thirteen of eighteen ganglia after periods longer than 8 weeks after cross-reinnervation with somatic axons. 4. Regenerated preganglionic or somatic nerve terminals were demonstrated around the ganglion cells using ZIO impregnation and electron-microscopy; the structure of these terminals was unchanged following regeneration into the ganglia, although many more synapses were formed by preganglionic terminals than by somatic terminals. 5. The facilitation of evoked synaptic potentials which occurs during repetitive stimulation of preganglionic axons was retained following their regeneration, whereas most synapses formed on ganglion cells by regenerating somatic axons showed facilitation of transmitter release during trains of stimuli, rather than the normal depression. 6. These observations suggest that the structure and electrical properties of adult mammalian autonomic motorneurones are not under neural control, but that these neurones do show some selectivity in the type of nerve which they will permit to form synapses on them. ImagesPlate 1Plate 2Plate 3Plate 4 PMID:4822587

  11. Enkephalinergic inhibition in parasympathetic ganglia of the urinary bladder of the cat.

    PubMed Central

    de Groat, W C; Kawatani, M

    1989-01-01

    1. Repetitive stimulation (10-20 Hz, 0.5-5 s duration) of the preganglionic nerves to ganglia on the surface of the urinary bladder of the cat produced a prolonged inhibition (duration, 30-65 s) of the postganglionic action potentials, elicited by low-frequency stimulation (0.25-1 Hz) of another preganglionic nerve to the same ganglion. 2. Intra-arterial administration of naloxone, an opiate antagonist (20-50 micrograms/kg), reduced the magnitude and duration of this heterosynaptic inhibition and also blocked the depression of ganglionic transmission elicited by the intra-arterial administration of leucine-enkephalin (0.1-10 micrograms/kg). 3. Naloxone did not alter adrenergic inhibition elicited by repetitive stimulation of the hypogastric nerve or exogenous noradrenaline. Naloxone did not alter the postganglionic firing elicited by single stimuli or trains of low-frequency (1-3 Hz) stimuli to the preganglionic nerves. 4. Heterosynaptic inhibition was not altered by the administration of antagonists for alpha-adrenergic (dihydroergotamine, prazosin, yohimbine), muscarinic (atropine), purinergic (theophylline) or GABAergic (picrotoxin) receptors. 5. A delta-selective opiate receptor agonist, DSLET (D-Ser2-leucine-enkephalin-Thr), inhibited parasympathetic ganglionic transmission in low doses (mean threshold dose, 0.02 microgram/kg, I.A.), whereas a mu-opiate receptor agonist, morphine sulphate, produced only a small depression in larger doses (mean threshold dose, 100 micrograms/kg, I.A.). Ethylketocyclazocine, which has an affinity for kappa-receptors did not alter transmission in relatively large doses (1 mg/kg, I.A.). 6. These findings coupled with previous immunocytochemical demonstrations of leucine-enkephalin-like immunoreactivity in preganglionic nerve terminals in bladder ganglia suggest that opioid peptides released endogenously from preganglionic nerves are involved in delta-receptor-mediated inhibitory mechanisms at cholinergic synapses in bladder ganglia. Images Fig. 1 PMID:2600844

  12. Frontal lobes, basal ganglia, temporal lobes--three sites for schizophrenia?

    PubMed

    Buchsbaum, M S

    1990-01-01

    This special issue of the Schizophrenia Bulletin focuses on three brain areas hypothesized to play a role in the etiology of schizophrenia--the frontal lobes, the basal ganglia, and the temporal lobes. Contributors to the issue review evidence from brain-imaging, post-mortem, and psychopharmacological studies that support the involvement of each of these important brain areas in schizophrenia. It is concluded that theories emphasizing cortical/subcortical interconnections rather than a single brain area provide the greatest challenge, and also the greatest promise, to schizophrenia researchers. PMID:2287928

  13. Uptake of nicotine and extracellular space markers by isolated rat ganglia in relation to receptor activation

    PubMed Central

    Brown, D. A.; Halliwell, J. V.; Scholfield, C. N.

    1971-01-01

    1. Uptake of 3H-nicotine by isolated rat superior cervical sympathetic (SCG) and nodose (NG) ganglia was measured in vitro. Depolarization of the ganglia by nicotine was measured electrically. 2. Nicotine depolarized the SCG but not the NG. The mean ED50 for depolarization was 5·3 × 10-6M. 3. Both ganglia accumulated nicotine when incubated in 3·1 × 10-5M 3H-nicotine: after 30 min incubation the ratios of tissue to medium concentrations were (mean ± S.E. of mean): SCG, 3·49 ± 0·13; NG, 2·50 ± 0·09. 4. Total water contents, estimated by drying to constant weight, were: SCG, 83·8 ± 0·12%; NG, 80·1 ± 0·21%. Extracellular spaces, measured as 3H-mannitol space, were: SCG, 38·8 ± 1·3; NG, 40·3 ± 0·8% wet weight. These values were not significantly altered by nicotine. 5. Correction for tissue fluid spaces indicated that the ratio of the mean intracellular fluid concentration to the extracellular fluid concentration for 3H-nicotine at 3·1 × 10-5M were: SCG, 7·4; NG, 5·6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3·1 × 10-7 and 1·6 × 10-4M. 6. When the nicotine concentration was sufficiently great (6·2 × 10-6M or more) to evoke large SCG depolarizations, hexamethonium (2·5 × 10-3M) reduced 3H-nicotine uptake by the SCG by up to 19% without affecting uptake by the NG, and thereby reduced the uptake difference between the two ganglia. With nicotine concentrations <6·2 × 10-6M, hexamethonium did not modify uptake by either ganglion. 7. It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine. PMID:5580695

  14. Functional correlates of exaggerated oscillatory activity in basal ganglia output in hemiparkinsonian rats.

    PubMed

    Brazhnik, Elena; Novikov, Nikolay; McCoy, Alex J; Cruz, Ana V; Walters, Judith R

    2014-11-01

    Exaggerated beta range (13-30Hz) synchronized activity is observed in the basal ganglia of Parkinson's disease (PD) patients during implantation of deep brain stimulation electrodes and is thought to contribute to the motor symptoms of this disorder. To explore the translational potential of similar activity observed in a rat model of PD, local field potentials (LFPs) and spiking activity in basal ganglia output were characterized in rats with unilateral dopamine cell lesion during a range of behaviors. A circular treadmill was used to assess activity during walking; hemiparkinsonian rats could maintain a steady gait when oriented ipsiversive to the lesioned hemisphere, but were less effective at walking when oriented contraversive to lesion. Dramatic increases in substantia nigra pars reticulata (SNpr) LFP oscillatory activity and spike-LFP synchronization were observed within the beta/low gamma range (12-40Hz) in the lesioned hemisphere, relative to the non-lesioned hemisphere, with the dominant frequency of spike-LFP entrainment and LFP power varying with behavioral state. At 3weeks postlesion, the mean dominant entrainment frequency during ipsiversive treadmill walking and grooming was 34Hz. Other behaviors were associated with lower mean entrainment frequencies: 27-28Hz during alert non-walking and REM, 17Hz during rest and 21Hz during urethane anesthesia with sensory stimulation. SNpr spike-LFP entrainment frequency was stable during individual treadmill walking epochs, but increased gradually over weeks postlesion. In contrast, SNpr LFP power in the 25-40Hz range was greatest at the initiation of each walking epoch, and decreased during walking to stabilize by 6min at 49% of initial values. Power was further modulated in conjunction with the 1.5s stepping rhythm. Administration of l-dopa improved contraversive treadmill walking in correlation with a reduction in SNpr 25-40Hz LFP power and spike synchronization in the dopamine cell lesioned hemisphere. These effects were reversed by the serotonergic 1A agonist, 8-OH-DPAT. While the prominent spike-LFP phase locking observed during ongoing motor activity in the hemiparkinsonian rats occurs at frequencies intriguingly higher than in PD patients, the synchronized activity in the SNpr of this animal model has much in common with oscillatory activity recorded from the basal ganglia of the PD patients. Results support the potential of this model for providing insight into relationships between synchronization of basal ganglia output induced by loss of dopamine and motor symptoms in PD. PMID:25084518

  15. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis.

    PubMed

    Wang, Cheng; Li, Yulei; Shi, Lei; Ren, Jie; Patti, Monica; Wang, Tao; de Oliveira, João R M; Sobrido, María-Jesús; Quintáns, Beatriz; Baquero, Miguel; Cui, Xiaoniu; Zhang, Xiang-Yang; Wang, Lianqing; Xu, Haibo; Wang, Junhan; Yao, Jing; Dai, Xiaohua; Liu, Juan; Zhang, Lu; Ma, Hongying; Gao, Yong; Ma, Xixiang; Feng, Shenglei; Liu, Mugen; Wang, Qing K; Forster, Ian C; Zhang, Xue; Liu, Jing-Yu

    2012-03-01

    Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC. PMID:22327515

  16. Cardiac abnormalities in liver cirrhosis.

    PubMed Central

    Lee, S S

    1989-01-01

    Cirrhosis is associated with several circulatory abnormalities. A hyperkinetic circulation characterized by increased cardiac output and decreased arterial pressure and peripheral resistance is typical. Despite this hyperkinetic circulation, some patients with alcoholic cirrhosis have subclinical cardiomyopathy with evidence of abnormal ventricular function unmasked by physiologic or pharmacologic stress. Florid congestive alcoholic cardiomyopathy develops in a small percentage, but the concurrent presence of cirrhosis seems to retard the occurrence of overt heart failure. Even nonalcoholic cirrhosis may be associated with latent cardiomyopathy, although overt heart failure is not observed. Tense ascites is associated with some cardiac compromise, and removing or mobilizing ascitic fluid by paracentesis or peritoneovenous shunting results in short-term increases in cardiac output. Cirrhosis also appears to be associated with a decreased risk of major coronary atherosclerosis and an increased risk of bacterial endocarditis. Small hemodynamically insignificant pericardial effusions may be seen in ascitic patients. The release of atrial natriuretic peptide appears to be unimpaired in cirrhosis, although the kidney may be hyporesponsive to its natriuretic effects. PMID:2690463

  17. Disorders caused by chromosome abnormalities

    PubMed Central

    Theisen, Aaron; Shaffer, Lisa G

    2010-01-01

    Many human genetic disorders result from unbalanced chromosome abnormalities, in which there is a net gain or loss of genetic material. Such imbalances often disrupt large numbers of dosage-sensitive, developmentally important genes and result in specific and complex phenotypes. Alternately, some chromosomal syndromes may be caused by a deletion or duplication of a single gene with pleiotropic effects. Traditionally, chromosome abnormalities were identified by visual inspection of the chromosomes under a microscope. The use of molecular cytogenetic technologies, such as fluorescence in situ hybridization and microarrays, has allowed for the identification of cryptic or submicroscopic imbalances, which are not visible under the light microscope. Microarrays have allowed for the identification of numerous new syndromes through a genotype-first approach in which patients with the same or overlapping genomic alterations are identified and then the phenotypes are described. Because many chromosomal alterations are large and encompass numerous genes, the ascertainment of individuals with overlapping deletions and varying clinical features may allow researchers to narrow the region in which to search for candidate genes. PMID:23776360

  18. Laboratory Validation of a Screening Model: Exploring the Interplay between Dissolution and Degradation Rates in Ganglia-Dominated Source Zones

    NASA Astrophysics Data System (ADS)

    Phelan, T. J.; Abriola, L. M.; Gibson, J. L.; Smits, K. M.; Christ, J.

    2013-12-01

    In-situ bioremediation is a widely applied treatment technology for source zones contaminated with dense non-aqueous phase liquids (DNAPLs). It is both economical and reasonably efficient for long-term management and closure of contaminated sites. A number of laboratory studies have demonstrated enhancement in chlorinated ethene dissolution rates due to the presence of dehalogenating microorganisms, which may lead to increased mass removal rates and shorter cleanup times. Previous modeling efforts have suggested this dissolution enhancement can be a factor of 10 or more when the contaminant is located in high saturation DNAPL pools. Yet, laboratory studies with DNAPL trapped as ganglia have suggested dissolution enhancement is often less than 10. This presentation investigates the interplay between dissolution and degradation rates in ganglia-contaminated source zones using a one-dimensional, simplified, steady-state, analytical solution to the advection-dispersion-reaction equation. A linear driving force model is employed to simulate ganglia dissolution. Degradation kinetics are approximated as zero- or first-order. Model predictions are independently compared to laboratory data available in the literature. Results indicate that dissolution enhancement predictions in ganglia-dominated source zones are often much less than those predicted assuming high saturation pools, suggesting that the presented model is a better tool for estimating bioenhanced dissolution in ganglia-contaminated regions. Furthermore, this screening model provides a remarkably good prediction of laboratory results and could provide practitioners with a useful tool for estimating the extent to which bioenhanced dissolution may aid in site closure strategies.

  19. Laboratory Assessment of a Screening Model: Exploring the Coupling between Dissolution and Degradation Rates in Ganglia-Dominated Source Zones

    NASA Astrophysics Data System (ADS)

    Phelan, T. J.; Abriola, L. M.; Gibson, J. L.; Smits, K. M.; Christ, J.

    2014-12-01

    In-situ bioremediation is a widely applied treatment technology for source zones contaminated with dense non-aqueous phase liquids (DNAPLs). It is both economical and reasonably efficient for long-term management and closure of contaminated sites. A number of laboratory studies have demonstrated enhancement in chlorinated ethene dissolution rates due to the presence of dehalogenating microorganisms, which may lead to increased mass removal rates and shorter cleanup times. Previous modeling efforts have suggested this dissolution enhancement can be a factor of 10 or more when the contaminant is located in high saturation DNAPL pools. Yet, laboratory studies with DNAPL trapped as ganglia have suggested dissolution enhancement is often less than 10. This presentation investigates the interplay between dissolution and degradation rates in ganglia-contaminated source zones using a one-dimensional, simplified, steady-state, analytical solution to the advection-dispersion-reaction equation. A linear driving force model is employed to simulate ganglia dissolution. Degradation kinetics are approximated as zero- or first-order. Model predictions are independently compared to laboratory data available in the literature. Results indicate that dissolution enhancement predictions in ganglia-dominated source zones are often much less than those predicted assuming high saturation pools, suggesting that the presented model is a better tool for estimating bioenhanced dissolution in ganglia-contaminated regions. Furthermore, this screening model provides a remarkably good prediction of laboratory results and could provide practitioners with a useful tool for estimating the extent to which bioenhanced dissolution may aid in site closure strategies.

  20. Abnormal Adherence of Sickle Erythrocytes to Cultured Vascular Endothelium

    PubMed Central

    Hebbel, Robert P.; Yamada, Osamu; Moldow, Charles F.; Jacob, Harry S.; White, James G.; Eaton, John W.

    1980-01-01

    The abnormal shape and poor deformability of the sickled erythrocyte (RBC) have generally been held responsible for the microvascular occlusions of sickle cell disease. However, there is no correlation between the clinical severity of this disease and the presence of sickled RBC. In searching for additional factors that might contribute to the pathophysiology of sickle cell disease, we have investigated the possibility that sickle RBC might be less than normally repulsive of the vascular endothelium. After RBC suspensions are allowed to settle onto plates of cultured human endothelial cells, normal RBC are completely removed by as few as six washes. In contrast, sickle RBC remain adherent despite multiple washes. On subconfluent culture plates, normal RBC are distributed randomly, whereas sickle RBC cluster around endothelial cells. Sickle RBC adherence is not enhanced by deoxygenation but does increase with increasing RBC density. The enzymatic removal of membrane sialic acid greatly diminishes the adherence of sickle RBC to endothelial cells, suggesting that sialic acid participates in this abnormal cell-cell interaction. Although net negative charge appears normal, sickle RBC mainfest an abnormal clumping of negative surface charge as demonstrated by localization of cationized ferritin. These abnormalities are reproduced in normal RBC loaded with nonechinocytogenic amounts of calcium. We conclude that sickle RBC adhere to vascular endothelial cells in vitro, perhaps caused by a calcium-induced aberration of membrane topography. This adherence may be a pathogenetic factor in the microvascular occlusions characteristic of sickle cell disease. Images PMID:7350195

  1. Unsupervised detection of abnormalities in medical images using salient features

    NASA Astrophysics Data System (ADS)

    Alpert, Sharon; Kisilev, Pavel

    2014-03-01

    In this paper we propose a new method for abnormality detection in medical images which is based on the notion of medical saliency. The proposed method is general and is suitable for a variety of tasks related to detection of: 1) lesions and microcalcifications (MCC) in mammographic images, 2) stenoses in angiographic images, 3) lesions found in magnetic resonance (MRI) images of brain. The main idea of our approach is that abnormalities manifest as rare events, that is, as salient areas compared to normal tissues. We define the notion of medical saliency by combining local patch information from the lightness channel with geometric shape local descriptors. We demonstrate the efficacy of the proposed method by applying it to various modalities, and to various abnormality detection problems. Promising results are demonstrated for detection of MCC and of masses in mammographic images, detection of stenoses in angiography images, and detection of lesions in brain MRI. We also demonstrate how the proposed automatic abnormality detection method can be combined with a system that performs supervised classification of mammogram images into benign or malignant/premalignant MCC's. We use a well known DDSM mammogram database for the experiment on MCC classification, and obtain 80% accuracy in classifying images containing premalignant MCC versus benign ones. In contrast to supervised detection methods, the proposed approach does not rely on ground truth markings, and, as such, is very attractive and applicable for big corpus image data processing.

  2. [Mineralization of the basal ganglia as the supposed cause of poor tolerance of zuclopenthixol in a patient with long-term untreated paranoid schizophrenia].

    PubMed

    Wichowicz, Hubert M; Wilkowska, Alina; Banecka-Majkutewicz, Zyta; Kummer, Łukasz; Konarzewska, Joanna; Raczak, Alicja

    2013-01-01

    Formations described as intracranial calcifications can appear in the course of diseases of the central nervous system, other systems and organs (e.g. endocrine), but also as a disorder of idiopathic character. They are frequently located in subcortical nuclei and usually constitute an incidental finding. This report presents the case of a patient suffering from paranoid schizophrenia for approximately 40 years, who did not agree to any treatment and was hospitalized against her will because she was the threat to the lives of others. She was treated with zuklopentixol resulting in positive symptoms reduction and considerable improvement in social functioning. Unfortunately neurological symptoms appeared: bradykinesis, rigidity--of the type of the lead pipe, balance, posture and gait abnormalities, disturbances in precise hands movements, double-sided Rossolimo's sign, plantar reflex without the participation of the big toe on the left. Neuroimaging studies have demonstrated changes in the form of lenticular nuclei calcification and reduction of signal intensity in posterior parts of both putamens. Neurological symptoms decreased significantly after switching to atypical neuroleptic (olanzapine), and the patient did not require any additional treatment. Mineralization of the basal ganglia can often be associated with psychiatric disorders and it shouldn't be neglected because it can require modification of pharmacotherapy or additional neurological treatment. PMID:24946467

  3. IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice

    PubMed Central

    Hisatsune, Chihiro; Miyamoto, Hiroyuki; Hirono, Moritoshi; Yamaguchi, Naohide; Sugawara, Takeyuki; Ogawa, Naoko; Ebisui, Etsuko; Ohshima, Toshio; Yamada, Masahisa; Hensch, Takao K.; Hattori, Mitsuharu; Mikoshiba, Katsuhiko

    2013-01-01

    The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca2+ channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking IP3R1 specifically in the cerebellum and brainstem experience dystonia and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific dystonic movements. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate IP3R1-dependent PC firing patterns in cerebellum in motor coordination and the expression of dystonia through the olivo-cerebellar pathway. PMID:24109434

  4. Particle-assisted abnormal grain growth

    NASA Astrophysics Data System (ADS)

    Holm, E. A.; Hoffmann, T. D.; Rollett, A. D.; Roberts, C. G.

    2015-08-01

    Abnormal grain growth is observed in systems that are nominally pinned by static particle dispersions. We used mesoscale simulations to examine grain growth in three-dimensional polycrystals containing stable, inert particles located at grain boundaries. In the absence of pinning particles, only normal grain growth occurs. When particles are present, some normal grain growth occurs, until a Zener-Smith pinned state is achieved. However, after a long incubation time, a few grains can thermally fluctuate away from their particle clouds and grow abnormally. The abnormal events are rare and stochastic. The abnormal grains are always among the largest initial grains, but most of the largest initial grains do not grow abnormally.

  5. Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

    PubMed Central

    Hsu, Sandy Chan; Sears, Renee L.; Lemos, Roberta R.; Quintáns, Beatriz; Huang, Alden; Spiteri, Elizabeth; Nevarez, Lisette; Mamah, Catherine; Zatz, Mayana; Pierce, Kerrie D.; Fullerton, Janice M.; Adair, John C.; Berner, Jon E.; Bower, Matthew; Brodaty, Henry; Carmona, Olga; Dobricić, Valerija; Fogel, Brent L.; García-Estevez, Daniel; Goldman, Jill; Goudreau, John L.; Hopfer, Suellen; Janković, Milena; Jaumà, Serge; Jen, Joanna C.; Kirdlarp, Suppachok; Klepper, Joerg; Kostić, Vladimir; Lang, Anthony E.; Linglart, Agnès; Maisenbacher, Melissa K.; Manyam, Bala V.; Mazzoni, Pietro; Miedzybrodzka, Zofia; Mitarnun, Witoon; Mitchell, Philip B.; Mueller, Jennifer; Novaković, Ivana; Paucar, Martin; Paulson, Henry; Simpson, Sheila A.; Svenningsson, Per; Tuite, Paul; Vitek, Jerrold; Wetchaphanphesat, Suppachok; Williams, Charles; Yang, Michele; Schofield, Peter R.; de Oliveira, João R. M.; Sobrido, María-Jesús

    2014-01-01

    Familial idiopathic basal ganglia calcification (IBGC) or Fahr’s disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient’s disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation. PMID:23334463

  6. Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification.

    PubMed

    Hsu, Sandy Chan; Sears, Renee L; Lemos, Roberta R; Quintáns, Beatriz; Huang, Alden; Spiteri, Elizabeth; Nevarez, Lisette; Mamah, Catherine; Zatz, Mayana; Pierce, Kerrie D; Fullerton, Janice M; Adair, John C; Berner, Jon E; Bower, Matthew; Brodaty, Henry; Carmona, Olga; Dobricić, Valerija; Fogel, Brent L; García-Estevez, Daniel; Goldman, Jill; Goudreau, John L; Hopfer, Suellen; Janković, Milena; Jaumà, Serge; Jen, Joanna C; Kirdlarp, Suppachok; Klepper, Joerg; Kostić, Vladimir; Lang, Anthony E; Linglart, Agnès; Maisenbacher, Melissa K; Manyam, Bala V; Mazzoni, Pietro; Miedzybrodzka, Zofia; Mitarnun, Witoon; Mitchell, Philip B; Mueller, Jennifer; Novaković, Ivana; Paucar, Martin; Paulson, Henry; Simpson, Sheila A; Svenningsson, Per; Tuite, Paul; Vitek, Jerrold; Wetchaphanphesat, Suppachok; Williams, Charles; Yang, Michele; Schofield, Peter R; de Oliveira, João R M; Sobrido, María-Jesús; Geschwind, Daniel H; Coppola, Giovanni

    2013-02-01

    Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41% of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation. PMID:23334463

  7. Highly efficient method for gene delivery into mouse dorsal root ganglia neurons.

    PubMed

    Yu, Lingli; Reynaud, Florie; Falk, Julien; Spencer, Ambre; Ding, Yin-Di; Baumlé, Véronique; Lu, Ruisheng; Castellani, Valérie; Yuan, Chonggang; Rudkin, Brian B

    2015-01-01

    The development of gene transfection technologies has greatly advanced our understanding of life sciences. While use of viral vectors has clear efficacy, it requires specific expertise and biological containment conditions. Electroporation has become an effective and commonly used method for introducing DNA into neurons and in intact brain tissue. The present study describes the use of the Neon® electroporation system to transfect genes into dorsal root ganglia neurons isolated from embryonic mouse Day 13.5-16. This cell type has been particularly recalcitrant and refractory to physical or chemical methods for introduction of DNA. By optimizing the culture condition and parameters including voltage and duration for this specific electroporation system, high efficiency (60-80%) and low toxicity (>60% survival) were achieved with robust differentiation in response to Nerve growth factor (NGF). Moreover, 3-50 times fewer cells are needed (6 × 10(4)) compared with other traditional electroporation methods. This approach underlines the efficacy of this type of electroporation, particularly when only limited amount of cells can be obtained, and is expected to greatly facilitate the study of gene function in dorsal root ganglia neuron cultures. PMID:25698920

  8. Real-time control of walking using recordings from dorsal root ganglia

    PubMed Central

    Holinski, B J; Everaert, D G; Mushahwar, V K; Stein, R B

    2013-01-01

    Objective The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the dorsal root ganglia. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modeled from recorded neural firing rates. These models were then used for closed-loop feedback. Main Results Overall, firing-rate based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48±13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development. PMID:23928579

  9. Latent Herpes Simplex Virus Infections in Sensory Ganglia of Hairless Mice Prevented by Acycloguanosine†

    PubMed Central

    Klein, Richard J.; Friedman-Kien, Alvin E.; DeStefano, Eugene

    1979-01-01

    Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals. PMID:230784

  10. Highly efficient method for gene delivery into mouse dorsal root ganglia neurons

    PubMed Central

    Yu, Lingli; Reynaud, Florie; Falk, Julien; Spencer, Ambre; Ding, Yin-Di; Baumlé, Véronique; Lu, Ruisheng; Castellani, Valérie; Yuan, Chonggang; Rudkin, Brian B.

    2015-01-01

    The development of gene transfection technologies has greatly advanced our understanding of life sciences. While use of viral vectors has clear efficacy, it requires specific expertise and biological containment conditions. Electroporation has become an effective and commonly used method for introducing DNA into neurons and in intact brain tissue. The present study describes the use of the Neon® electroporation system to transfect genes into dorsal root ganglia neurons isolated from embryonic mouse Day 13.5–16. This cell type has been particularly recalcitrant and refractory to physical or chemical methods for introduction of DNA. By optimizing the culture condition and parameters including voltage and duration for this specific electroporation system, high efficiency (60–80%) and low toxicity (>60% survival) were achieved with robust differentiation in response to Nerve growth factor (NGF). Moreover, 3–50 times fewer cells are needed (6 × 104) compared with other traditional electroporation methods. This approach underlines the efficacy of this type of electroporation, particularly when only limited amount of cells can be obtained, and is expected to greatly facilitate the study of gene function in dorsal root ganglia neuron cultures. PMID:25698920

  11. Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory

    PubMed Central

    Koster, Raphael; Guitart-Masip, Marc; Dolan, Raymond J.; Düzel, Emrah

    2015-01-01

    The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for. PMID:26420783

  12. Mitochondrial Toxins in Basal Ganglia Disorders: From Animal Models to Therapeutic Strategies

    PubMed Central

    Bonsi, P; Cuomo, D; Martella, G; Sciamanna, G; Tolu, M; Calabresi, P; Bernardi, G; Pisani, A

    2006-01-01

    Current knowledge of the pathogenesis of basal ganglia disorders, such as Huntington’s disease (HD) and Parkinson’s disease (PD) appoints a central role to a dysfunction in mitochondrial metabolism. The development of animal models, based upon the use of mitochondrial toxins has been successfully introduced to reproduce human disease, leading to important acquisitions. Most notably, experimental evidence supports the existence, within basal ganglia, of a peculiar regional vulnerability to distinct mitochondrial toxins. MPTP and rotenone, both selective inhibitors of mitochondrial complex I have been extensively used to mimic PD. Accordingly, in human PD, a specific dysfunction of complex I activity was found in vulnerable dopaminergic neurons of the substantia nigra. Conversely, in HD a selective impairment of mitochondrial succinate dehydrogenase, key enzyme in complex II activity was found in medium spiny neurons of the caudate-putamen. The relevance of such finding is further demonstrated by the evidence that toxins able to primarily target mitochondrial complex II, such as malonic acid and 3-nitropropionic acid (3-NP), strikingly reproduce the main phenotypic and pathological features of HD. Despite the advances obtained from these experimental models, a deeper understanding of the molecular and cellular mechanisms underlying such neuronal vulnerability is lacking. The present review provides a brief survey of currently utilized animal models of mitochondrial intoxication, in attempt to address the cellular mechanisms triggered by energy metabolism failure and to identify potential therapeutic targets. PMID:18615133

  13. Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia

    PubMed Central

    Chatzi, Christina; Brade, Thomas; Duester, Gregg

    2011-01-01

    Although retinoic acid (RA) has been implicated as an extrinsic signal regulating forebrain neurogenesis, the processes regulated by RA signaling remain unclear. Here, analysis of retinaldehyde dehydrogenase mutant mouse embryos lacking RA synthesis demonstrates that RA generated by Raldh3 in the subventricular zone of the basal ganglia is required for GABAergic differentiation, whereas RA generated by Raldh2 in the meninges is unnecessary for development of the adjacent cortex. Neurospheres generated from the lateral ganglionic eminence (LGE), where Raldh3 is highly expressed, produce endogenous RA, which is required for differentiation to GABAergic neurons. In Raldh3?/? embryos, LGE progenitors fail to differentiate into either GABAergic striatal projection neurons or GABAergic interneurons migrating to the olfactory bulb and cortex. We describe conditions for RA treatment of human embryonic stem cells that result in efficient differentiation to a heterogeneous population of GABAergic interneurons without the appearance of GABAergic striatal projection neurons, thus providing an in vitro method for generation of GABAergic interneurons for further study. Our observation that endogenous RA is required for generation of LGE-derived GABAergic neurons in the basal ganglia establishes a key role for RA signaling in development of the forebrain. PMID:21532733

  14. Neuroanatomy of the optic ganglia and central brain of the water flea Daphnia magna (Crustacea, Cladocera).

    PubMed

    Kress, Timm; Harzsch, Steffen; Dircksen, Heinrich

    2016-03-01

    We reveal the neuroanatomy of the optic ganglia and central brain in the water flea Daphnia magna by use of classical neuroanatomical techniques such as semi-thin sectioning and neuronal backfilling, as well as immunohistochemical markers for synapsins, various neuropeptides and the neurotransmitter histamine. We provide structural details of distinct neuropiles, tracts and commissures, many of which were previously undescribed. We analyse morphological details of most neuron types, which allow for unravelling the connectivities between various substructural parts of the optic ganglia and the central brain and of ascending and descending connections with the ventral nerve cord. We identify 5 allatostatin-A-like, 13 FMRFamide-like and 5 tachykinin-like neuropeptidergic neuron types and 6 histamine-immunoreactive neuron types. In addition, novel aspects of several known pigment-dispersing hormone-immunoreactive neurons are re-examined. We analyse primary and putative secondary olfactory pathways and neuronal elements of the water flea central complex, which displays both insect- and decapod crustacean-like features, such as the protocerebral bridge, central body and lateral accessory lobes. Phylogenetic aspects based upon structural comparisons are discussed as well as functional implications envisaging more specific future analyses of ecotoxicological and endocrine disrupting environmental chemicals. PMID:26391274

  15. fMRI of cocaine self-administration in macaques reveals functional inhibition of basal ganglia.

    PubMed

    Mandeville, Joseph B; Choi, Ji-Kyung; Jarraya, Bechir; Rosen, Bruce R; Jenkins, Bruce G; Vanduffel, Wim

    2011-05-01

    Disparities in cocaine-induced neurochemical and metabolic responses between human beings and rodents motivate the use of non-human primates (NHP) to model consequences of repeated cocaine exposure in human subjects. To characterize the functional response to cocaine infusion in NHP brain, we employed contrast-enhanced fMRI during both non-contingent injection of drug and self-administration of cocaine in the magnet. Cocaine robustly decreased cerebral blood volume (CBV) throughout basal ganglia and motor/pre-motor cortex and produced subtle functional inhibition of prefrontal cortex. No brain regions exhibited significant elevation of CBV in response to cocaine challenge. Theses effects in NHP brain are opposite in sign to the cocaine-induced fMRI response in rats, but consistent with previous measurements in NHP based on glucose metabolism. Because the striatal ratio of D2 to D1 receptors is larger in human beings and NHP than rats, we hypothesize that the inhibitory effects of D2 receptor binding dominate the functional response in primates, whereas excitatory D1 receptor stimulation predominates in the rat. If the NHP accurately models the human response to cocaine, downregulation of D2 receptors in human cocaine-abusing populations can be expected to blunt cocaine-induced functional responses, contributing to the weak and variable fMRI responses reported in human basal ganglia following cocaine infusion. PMID:21307843

  16. Transcriptional changes in sensory ganglia associated with primary afferent axon collateral sprouting in spared dermatome model

    PubMed Central

    Harrison, Benjamin J.; Venkat, Gayathri; Hutson, Thomas; Rau, Kristofer K.; Bunge, Mary Bartlett; Mendell, Lorne M.; Gage, Fred H.; Johnson, Richard D.; Hill, Caitlin; Rouchka, Eric C.; Moon, Lawrence; Petruska, Jeffrey C.

    2015-01-01

    Primary afferent collateral sprouting is a process whereby non-injured primary afferent neurons respond to some stimulus and extend new branches from existing axons. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity (e.g., [1], [2], [3], [4], [5], [6], [7], [8], [9]). In the model used here (the “spared dermatome” model), the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Investigations of gene expression changes associated with collateral sprouting can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatments to promote functional recovery for spinal cord injury and other similar conditions. This report includes raw gene expression data files from microarray experiments in order to study the gene regulation in spared sensory ganglia in the initiation (7 days) and maintenance (14 days) phases of the spared dermatome model relative to intact (“naïve”) sensory ganglia. Data has been deposited into GEO (GSE72551). PMID:26697387

  17. Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory.

    PubMed

    Koster, Raphael; Guitart-Masip, Marc; Dolan, Raymond J; Düzel, Emrah

    2015-12-01

    The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for. PMID:26420783

  18. Microstructural Changes within the Basal Ganglia Differ between Parkinson Disease Subtypes

    PubMed Central

    Nagae, Lidia M.; Honce, Justin M.; Tanabe, Jody; Shelton, Erika; Sillau, Stefan H.; Berman, Brian D.

    2016-01-01

    Diffusion tensor imaging (DTI) of the substantia nigra has shown promise in detecting and quantifying neurodegeneration in Parkinson disease (PD). It remains unknown, however, whether differences in microstructural changes within the basal ganglia underlie PD motor subtypes. We investigated microstructural changes within the basal ganglia of mild to moderately affected PD patients using DTI and sought to determine if microstructural changes differ between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes. Fractional anisotropy, mean diffusivity, radial, and axial diffusivity were obtained from bilateral caudate, putamen, globus pallidus, and substantia nigra of 21 PD patients (12 TD and 9 PIGD) and 20 age-matched healthy controls. T-tests and ANOVA methods were used to compare PD patients, subtypes, and controls, and Spearman correlations tested for relationships between DTI and clinical measures. We found our cohort of PD patients had reduced fractional anisotropy within the substantia nigra and increased mean and radial diffusivity within the substantia nigra and globus pallidus compared to controls, and that changes within those structures were largely driven by the PIGD subtype. Across all PD patients fractional anisotropy within the substantia nigra correlated with disease stage, while in PIGD patients increased diffusivity within the globus pallidus correlated with disease stage and motor severity. We conclude that PIGD patients have more severely affected microstructural changes within the substantia nigra compared to TD, and that microstructural changes within the globus pallidus may be particularly relevant for the manifestation of the PIGD subtype. PMID:26941615

  19. Increase of glucose consumption in basal ganglia, thalamus and frontal cortex of patients with spasmodic torticollis

    SciTech Connect

    Grassi, F.; Bressi, S.; Antoni, M.

    1994-05-01

    The pathophysiology of spasmodic torticollis, a focal dystonia involving neck muscles, is still unclear. Positron emission tomography (PET) studies showed either an increase as well as a decrease of regional cerebral metabolic rate of glucose (rCMRglu) in basal ganglia. In the present study, [18F]FDG and PET was used to measure rCMRglu in 10 patients with spasmodic torticollis (mean age 50.37 {plus_minus} 11.47) and 10 age matched controls. All cases with a short disease duration, were untreated. A factorial analysis of variance revealed a significant bilateral increase of glucose consumption in caudate nucleus and pallidum/putamen complex (p>0.004) and in the cerebellum (p>0.001). The rCMRglu increase in the motor/premotor cortex and in the thalamus reached a trend towards significance (p<0.05). These preliminary data show enhanced metabolism in basal ganglia and cerebellum as the functional correlate of focal dystonia. A recently proposed model suggests that dystonia would be the consequence of a putaminal hyperactivity, leading to the breakdown of the pallidal inhibitory control on thalamus and thalamo-cortical projections.

  20. Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons

    PubMed Central

    Bellamy, Jamie; Bowen, Elizabeth J.; Russo, Andrew F.; Durham, Paul L.

    2006-01-01

    Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four-fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T-type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen-activated protein kinases Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons. PMID:16630053

  1. Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

    SciTech Connect

    Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A. )

    1991-02-01

    Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ({sup 125}I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of control cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease.

  2. Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia

    SciTech Connect

    Weiner, D.M. Howard Hughes Medical Inst., Bethesda, MD ); Levey, A.I. Johns Hopkins Univ., Baltimore, MD ); Brann, M.R. )

    1990-09-01

    Within the basal ganglia, acetylcholine and dopamine play a central role in the extrapyramidal control of motor function. The physiologic effects of these neurotransmitters are mediated by a diversity of receptor subtypes, several of which have now been cloned. Muscarinic acetylcholine receptors are encoded by five genes (m1-m5), and of the two known dopamine receptor subtypes (D1 and D2) the D2 receptor gene has been characterized. To gain insight into the physiological roles of each of these receptor subtypes, the authors prepared oligodeoxynucleotide probes to localize receptor subtype mRNAs within the rat striatum and substantia nigra by in situ hybridization histochemistry. Within the striatum, three muscarinic (m1, m2, m4) receptor mRNAs and the D2 receptor mRNA were detected. The m1 mRNA was expressed in most neurons; the m2 mRNA, in neurons which were both very large and rare; and the m4 and D2 mRNAs, in 40-50% of the neurons, one-third of which express both mRNAs. Within the substantia nigra, pars compacta, only the m5 and D2 mRNAs were detected, and most neurons expressed both mRNAs. These data provide anatomical evidence for the identity of the receptor subtypes which mediate the diverse effects of muscarinic and dopaminergic drugs on basal ganglia function.

  3. Transcriptional changes in sensory ganglia associated with primary afferent axon collateral sprouting in spared dermatome model.

    PubMed

    Harrison, Benjamin J; Venkat, Gayathri; Hutson, Thomas; Rau, Kristofer K; Bunge, Mary Bartlett; Mendell, Lorne M; Gage, Fred H; Johnson, Richard D; Hill, Caitlin; Rouchka, Eric C; Moon, Lawrence; Petruska, Jeffrey C

    2015-12-01

    Primary afferent collateral sprouting is a process whereby non-injured primary afferent neurons respond to some stimulus and extend new branches from existing axons. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity (e.g., [1], [2], [3], [4], [5], [6], [7], [8], [9]). In the model used here (the "spared dermatome" model), the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Investigations of gene expression changes associated with collateral sprouting can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatments to promote functional recovery for spinal cord injury and other similar conditions. This report includes raw gene expression data files from microarray experiments in order to study the gene regulation in spared sensory ganglia in the initiation (7 days) and maintenance (14 days) phases of the spared dermatome model relative to intact ("naïve") sensory ganglia. Data has been deposited into GEO (GSE72551). PMID:26697387

  4. Cardiorespiratory fitness and its association with thalamic, hippocampal, and basal ganglia volumes in multiple sclerosis

    PubMed Central

    Motl, Robert W.; Pilutti, Lara A.; Hubbard, Elizabeth A.; Wetter, Nathan C.; Sosnoff, Jacob J.; Sutton, Bradley P.

    2015-01-01

    Background There is little known about cardiorespiratory fitness and its association with volumes of the thalamus, hippocampus, and basal ganglia in multiple sclerosis (MS). Such inquiry is important for identifying a possible behavioral approach (e.g., aerobic exercise training) that might change volumes of deep gray matter (DGM) structures associated with cognitive and motor functions in MS. Purpose This study examined the association between cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal ganglia in MS. Method We enrolled 35 persons with MS who underwent a maximal exercise test for measuring cardiorespiratory fitness as peak oxygen consumption (VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen, and pallidum were calculated from 3D T1-weighted structural brain images. We examined associations using partial (pr) correlations controlling for demographic and clinical variables. Results VO2peak was significantly associated with composite scaled volumes of the caudate(pr = .47, p < .01), putamen (pr = .44, p < .05), pallidum (pr = .40, p < .05), and hippocampus (pr = .42, p < .05), but not thalamus (pr = .31, p = .09), when controlling for sex, age, disability, and duration of MS. Conclusion Our results provide novel evidence that cardiorespiratory fitness is associated with volumes of DGM structures that are involved in motor and cognitive functions in MS. PMID:25844320

  5. Basal Ganglia Neuronal Activity during Scanning Eye Movements in Parkinson’s Disease

    PubMed Central

    Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

    2013-01-01

    The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control. PMID:24223158

  6. Competing basal ganglia pathways determine the difference between stopping and deciding not to go

    PubMed Central

    Dunovan, Kyle; Lynch, Brighid; Molesworth, Tara; Verstynen, Timothy

    2015-01-01

    The architecture of corticobasal ganglia pathways allows for many routes to inhibit a planned action: the hyperdirect pathway performs fast action cancellation and the indirect pathway competitively constrains execution signals from the direct pathway. We present a novel model, principled off of basal ganglia circuitry, that differentiates control dynamics of reactive stopping from intrinsic no-go decisions. Using a nested diffusion model, we show how reactive braking depends on the state of an execution process. In contrast, no-go decisions are best captured by a failure of the execution process to reach the decision threshold due to increasing constraints on the drift rate. This model accounts for both behavioral and functional MRI (fMRI) responses during inhibitory control tasks better than alternative models. The advantage of this framework is that it allows for incorporating the effects of context in reactive and proactive control into a single unifying parameter, while distinguishing action cancellation from no-go decisions. DOI: http://dx.doi.org/10.7554/eLife.08723.001 PMID:26402462

  7. Abnormalities of the Erythrocyte Membrane

    PubMed Central

    Gallagher, Patrick G.

    2014-01-01

    Synopsis Primary abnormalities of the erythrocyte membrane, including the hereditary spherocytosis and hereditary elliptocytosis syndromes, are an important group of inherited hemolytic anemias. Classified by distinctive morphology on peripheral blood smear, these disorders are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Once considered routine, growing recognition of the longterm risks of splenectomy, including cardiovascular disease, thrombotic disorders, and pulmonary hypertension, as well as the emergence of penicillin-resistant pneumococci, a concern for infection in overwhelming postsplenectomy infection, have led to re-evaluation of the role of splenectomy. Current management guidelines acknowledge these important considerations when entertaining splenectomy and recommend detailed discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy. PMID:24237975

  8. Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

    PubMed

    Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

    2015-04-01

    The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. PMID:25595501

  9. Normal and abnormal development of an identified leech motor neuron.

    PubMed

    Kuwada, J Y

    1984-02-01

    In embryonic and mature leeches, the identified L motor neuron, which innervates the longitudinal muscles of the contralateral half body segment, can be identified by the location and relatively large size of its cell body. Here the morphological and physiological development of the L motor neuron has been investigated by intracellular recording and dye-filling techniques in normal and abnormal embryonic leeches. Normally the L motor neuron growth cone projects from the cell body at about the same time as from many other neurons located in the lateral part of the ganglion, including the P mechanosensory neurons. The L motor axon, like many other leech axons, projects directly into the appropriate pathway. The L motor neuron does not initially extend an excessive number of axons followed by elimination of the inappropriate ones. Its growth cone is tapered and relatively free of filopodia and grows out of the ganglion in the contralateral posterior nerve behind the growth cone of the primary peripheral axon of the dorsal P mechanosensory cell, which is one of the earliest axons in the posterior root. Occasionally the bilateral halves of the germinal plate fail to fuse resulting in an embryo with separated but intact half ganglia, body wall, and skin. In such embryos the L motor neuron axons cannot grow out of the contralateral posterior nerve since it is not available. Instead they grow out a variety of ipsilateral nerves and/or connective tracts. The P mechanosensory cells, which normally grow out of the ganglion in specific ipsilateral nerves, extend their axons along their normal pathways. In these abnormal embryos the L motor neurons did not preferentially grow into the ipsilateral posterior nerve, normally the pathway taken by the bilateral homologue and the nerve most similar to the L motor neuron's normal pathway. The failure of these L neurons to either consistently choose or avoid the ipsilateral posterior root suggests that the bilateral homologues ignore one another's pathfinding cues or that such cues are missing or changed in these embryos. The axons of the P neurons, however, appear to require no cues or interactions with contralateral structures or cells for normal development. PMID:6716040

  10. Superordinate Shape Classification Using Natural Shape Statistics

    ERIC Educational Resources Information Center

    Wilder, John; Feldman, Jacob; Singh, Manish

    2011-01-01

    This paper investigates the classification of shapes into broad natural categories such as "animal" or "leaf". We asked whether such coarse classifications can be achieved by a simple statistical classification of the shape skeleton. We surveyed databases of natural shapes, extracting shape skeletons and tabulating their parameters within each…

  11. Superordinate Shape Classification Using Natural Shape Statistics

    ERIC Educational Resources Information Center

    Wilder, John; Feldman, Jacob; Singh, Manish

    2011-01-01

    This paper investigates the classification of shapes into broad natural categories such as "animal" or "leaf". We asked whether such coarse classifications can be achieved by a simple statistical classification of the shape skeleton. We surveyed databases of natural shapes, extracting shape skeletons and tabulating their parameters within each…

  12. Superordinate shape classification using natural shape statistics

    PubMed Central

    Wilder, John; Feldman, Jacob; Singh, Manish

    2011-01-01

    This paper investigates the classification of shapes into broad natural categories such as animal or leaf. We asked whether such coarse classifications can be achieved by a simple statistical classification of the shape skeleton. We surveyed databases of natural shapes, extracting shape skeletons and tabulating their parameters within each class, seeking shape statistics that effectively discriminated the classes. We conducted two experiments in which human subjects were asked to classify novel shapes into the same natural classes. We compared subjects’ classifications to those of a naive Bayesian classifier based on the natural shape statistics, and found good agreement. We conclude that human superordinate shape classifications can be well understood as involving a simple statistical classification of the shape skeleton that has been “tuned” to the natural statistics of shape. PMID:21440250

  13. The Kabuki syndrome: four patients with oral abnormalities.

    PubMed

    Petzold, D; Kratzsch, E; Opitz, Ch; Tinschert, S

    2003-02-01

    The aim of this paper is to report the oral signs and symptoms of four patients with Kabuki syndrome. All had oral abnormalities affecting the palate, teeth, and/or lips, including wide spacing between the teeth, screwdriver-shaped upper incisors, hypodontia, delayed tooth eruption, narrow spacing in the upper canine area, large pulp chambers of the upper incisors and permanent molars, external root resorption of the upper central incisors and permanent molars, a division of the lower third of the root canal in normally one-rooted teeth, tooth retention, retrognathia of the upper jaw, a high palate or cleft lip/palate, and microforms of lower lip fistula. PMID:12608719

  14. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract.

    PubMed

    Ramanathan, Subramaniyan; Kumar, Devendra; Khanna, Maneesh; Al Heidous, Mahmoud; Sheikh, Adnan; Virmani, Vivek; Palaniappan, Yegu

    2016-02-28

    Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management. PMID:26981222

  15. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract

    PubMed Central

    Ramanathan, Subramaniyan; Kumar, Devendra; Khanna, Maneesh; Al Heidous, Mahmoud; Sheikh, Adnan; Virmani, Vivek; Palaniappan, Yegu

    2016-01-01

    Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management. PMID:26981222

  16. Evaluation of abnormal liver function tests

    PubMed Central

    Limdi, J; Hyde, G

    2003-01-01

    Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more common with the introduction of automated routine laboratory testing. Not all persons with one or more abnormalities in these tests actually have liver disease. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review. PMID:12840117

  17. INTRACRANIAL GERM CELL TUMORS WITH MTOR MUTATION ARE COMMON IN BASAL GANGLIA

    PubMed Central

    Nishikawa, Ryo; Fukuoka, Kohei; Ichimura, Koichi

    2014-01-01

    BACKGROUND: Intracranial germ cell tumors (iGCTs) are the second most common CNS tumors in patients under 14 years old in Japan. But, their molecular genetic profile is largely unknown. METHODS: We have analyzed a total of 198 germ cell tumors (GCTs) including 133 iGCTs (69 pure germinomas, 56 non-germinomatous GCTs and 8 metastatic tumors) as well as 65 testicular germ cell tumors (tGCTs) (39 seminomas and 26 non-seminoma GCTs) were collected from 13 centers participating in the Intracranial Germ Cell Tumor Consortium in Japan. Somatic mutations in all coding exons were investigated by whole exome sequencing (WES) using SureSelectXT Human All Exon v4 and a GAIIx or HiSeq 2000 system in 41 tumors and the matched normal DNAs. Targeted sequencing with a set of custom made PCR primers was performed using either an IonTorrent PGM or Proton System. The results were integrated with the patients' clinical information that was available for 124 iGCT patients. RESULTS: On average, 15.4 non-synonymous somatic mutations were observed in each tumor, ranging from 1 to 140 by WES in 41 iGCTs. MTOR was the second most frequently mutated in both iGCTs (9 cases, 7%) and tGCTs (6%). Collectively, the genes involved in the PI3K/MTOR pathway (e.g., MTOR, PTEN) were mutated in 13% of all GCTs. Clinical parameters of the 9 iGCTs with MTOR mutation were: median age of onset = 15 years old; 7 males and 2 females; 5 germinomas, 3 teratomas and one yolk sac tumor; 5 basal ganglia tumors, 2 pineal tumors, one neurohypophyseal tumor and a medulla oblongata tumor. Age, sex, histology and clinical behavior are within the scope of iGCT except for extraordinary high frequency of basal ganglia GCTs. CONCLUSIONS: iGCTs with MTOR mutation are frequent in iGCTs in basal ganglia. SECONDARY CATEGORY: Pediatrics.

  18. Biochemical abnormalities in Pearson syndrome.

    PubMed

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders. PMID:25691415

  19. [Renal abnormalities in ankylosing spondylitis].

    PubMed

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. PMID:22520483

  20. Semen abnormalities with SSRI antidepressants.

    PubMed

    2015-01-01

    Despite decades of widespread use, the adverse effect profile of "selective" serotonin reuptake inhibitor (SSRI) antidepressants has still not been fully elucidated. Studies in male animals have shown delayed sexual development and reduced fertility. Three prospective cohort studies conducted in over one hundred patients exposed to an SSRI for periods ranging from 5 weeks to 24 months found altered semen param-eters after as little as 3 months of exposure: reduced sperm concentration, reduced sperm motility, a higher percentage of abnormal spermatozoa, and increased levels of sperm DNA fragmentation. One clinical trial showed growth retardation in children considered depressed who were exposed to SSRls. SSRls may have endocrine disrupting properties. Dapoxetine is a short-acting serotonin reuptake inhibitor that is chemically related to fluoxetine and marketed in the European Union for men complaining of premature ejaculation. But the corresponding European summary of product characteristics does not mention any effects on fertility. In practice, based on the data available as of mid-2014, the effects of SSRI exposure on male fertility are unclear. However, it is a risk that should be taken into account and pointed out to male patients who would like to father a child or who are experiencing fertility problems. PMID:25729824

  1. The XXXXY Sex Chromosome Abnormality

    PubMed Central

    Barr, M. L.; Carr, D. H.; Pozsonyi, J.; Wilson, R. A.; Dunn, H. G.; Jacobson, T. S.; Miller, J. R.; Chown, B.

    1962-01-01

    The most common sex chromosome complex in sex chromatin-positive males with Klinefelter's syndrome is XXY. When the complex is XXYY or XXXY, the clinical findings do not seem to differ materially from those seen in XXY subjects, although more patients with these intersexual chromosome complements need to be studied to establish possible phenotypical expressions of the chromosomal variants. Two male children with an XXXXY sex chromosome abnormality are described. The data obtained from the study of these cases and five others described in the literature suggest that the XXXXY patient is likely to have congenital defects not usually seen in the common form of the Klinefelter syndrome. These include a triad of (1) skeletal anomalies (including radioulnar synostosis), (2) hypogenitalism (hypoplasia of penis and scrotum, incomplete descent of testes and defective prepubertal development of seminiferous tubules), and (3) greater risk of severe mental deficiency. That the conclusions are based on data from a small number of patients is emphasized, together with the need for a cytogenetic survey of a large control or unselected population. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10 PMID:13969480

  2. Modulation of Tyrosine Hydroxylase, Neuropeptide Y, Glutamate, and Substance P in Ganglia and Brain Areas Involved in Cardiovascular Control after Chronic Exposure to Nicotine

    PubMed Central

    Ferrari, Merari F. R.; Coelho, Emerson F.; Farizatto, Karen L. G.; Chadi, Gerson; Fior-Chadi, Debora R.

    2011-01-01

    Considering that nicotine instantly interacts with central and peripheral nervous systems promoting cardiovascular effects after tobacco smoking, we evaluated the modulation of glutamate, tyrosine hydroxylase (TH), neuropeptide Y (NPY), and substance P (SP) in nodose/petrosal and superior cervical ganglia, as well as TH and NPY in nucleus tractus solitarii (NTS) and hypothalamic paraventricular nucleus (PVN) of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after 8 weeks of nicotine exposure. Immunohistochemical and in situ hybridization data demonstrated increased expression of TH in brain and ganglia related to blood pressure control, preferentially in SHR, after nicotine exposure. The alkaloid also increased NPY immunoreactivity in ganglia, NTS, and PVN of SHR, in spite of decreasing its receptor (NPY1R) binding in NTS of both strains. Nicotine increased SP and glutamate in ganglia. In summary, nicotine positively modulated the studied variables in ganglia while its central effects were mainly constrained to SHR. PMID:21822476

  3. Radiologic atlas of pulmonary abnormalities in children

    SciTech Connect

    Singleton, E.B.; Wagner, M.L.; Dutton, R.V.

    1988-01-01

    This book is an atlas about thoracic abnormalities in infants and children. The authors include computed tomographic, digital subtraction angiographic, ultrasonographic, and a few magnetic resonance (MR) images. They recognize and discuss how changes in the medical treatment of premature infants and the management of infection and pediatric tumors have altered some of the appearances and considerations in these diseases. Oriented toward all aspects of pulmonary abnormalities, the book starts with radiographic techniques and then discusses the normal chest, the newborn, infections, tumors, and pulmonary vascular diseases. There is comprehensive treatment of mediastinal abnormalities and a discussion of airway abnormalities.

  4. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation.

    PubMed

    Israelashvili, Michal; Loewenstern, Yocheved; Bar-Gad, Izhar

    2015-07-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  5. Abnormal High-Frequency Burst Firing of Cerebellar Neurons in Rapid-Onset Dystonia-Parkinsonism

    PubMed Central

    Fremont, Rachel; Calderon, D. Paola; Maleki, Sara

    2014-01-01

    Loss-of-function mutations in the ?3 isoform of the Na+/K+ ATPase (sodium pump) are responsible for rapid-onset dystonia parkinsonism (DYT12). Recently, a pharmacological model of DYT12 was generated implicating both the cerebellum and basal ganglia in the disorder. Notably, partially blocking sodium pumps in the cerebellum was necessary and sufficient for induction of dystonia. Thus, a key question that remains is how partially blocking sodium pumps in the cerebellum induces dystonia. In vivo recordings from dystonic mice revealed abnormal high-frequency bursting activity in neurons of the deep cerebellar nuclei (DCN), which comprise the bulk of cerebellar output. In the same mice, Purkinje cells, which provide strong inhibitory drive to DCN cells, also fired in a similarly erratic manner. In vitro studies demonstrated that Purkinje cells are highly sensitive to sodium pump dysfunction that alters the intrinsic pacemaking of these neurons, resulting in erratic burst firing similar to that identified in vivo. This abnormal firing abates when sodium pump function is restored and dystonia caused by partial block of sodium pumps can be similarly alleviated. These findings suggest that persistent high-frequency burst firing of cerebellar neurons caused by sodium pump dysfunction underlies dystonia in this model of DYT12. PMID:25164667

  6. [Effect of Na(+), K(+)-pump inhibitors on the sensory ganglia neurite growth].

    PubMed

    Penniia?nen, V A; Lopatina, E V; Tsyrlin, V A; Krylov, B V

    2008-03-01

    Inhibitors of Na(+), K(+)-pump belonging to the class of cardiac glycosides were investigated in organotypic tissue culture of dorsal root ganglia cells of 10-12 days old chicken embryos. The data obtained show that the application of cardiac glycosides (strophantin K and digoxin) in a wide range of concentrations controls the neurite growth in sensory neurons in the dose-dependent manner. It was shown, that at the concentrations of cardiac glycoside exceeding 1 x 10(-6) M the growth of neurites was totally inhibited. Our data indicate that cardiac glycoside have the down-regulation effect on the neurite growth. The data obtained indicate that the Na(+), K(+)-ATPase is involved in the control of the process of neurite growth as a signal transducer. PMID:18507162

  7. Different susceptibility of medial temporal lobe and basal ganglia atrophy rates to vascular risk factors

    PubMed Central

    de Jong, Laura W.; Forsberg, Lars E.; Vidal, Jean-Sébastien; Sigurdsson, Sigurdur; Zijdenbos, Alex P.; Garcia, Melissa; Eiriksdottir, Gudny; Gudnason, Vilmundur; van Buchem, Mark A.; Launer, Lenore J.

    2013-01-01

    Atrophy of medial temporal lobe (MTL) and basal ganglia (BG) are characteristic of various neurodegenerative diseases in older people. In search of potentially modifiable factors that lead to atrophy in these structures, we studied the association of vascular risk factors to atrophy of MTL and BG in 368 non-demented men and women [b. 1907–1935] who participated in the Age, Gene/Environment, Susceptibility - Reykjavik Study. A fully automated segmentation pipeline estimated volumes of MTL and BG from whole brain MRI performed at baseline and 2.4 years later. Linear regression models showed higher systolic and diastolic blood pressures and the presence of Apo E ?4 were independently associated with increased atrophy of MTL but no association of vascular risk factors with atrophy of BG. The different susceptibility of MTL and BG atrophy to the presence of vascular risk factors suggests the relatively preserved perfusion of BG when vascular risk factors are present. PMID:23992618

  8. Online Feedback Control of Functional Electrical Stimulation Using Dorsal Root Ganglia Recordings

    PubMed Central

    Bauman, Matthew J.; Bruns, Tim M.; Wagenaar, Joost B.; Gaunt, Robert A.; Weber, Douglas J.

    2012-01-01

    In neuroprostheses that use functional electrical stimulation (FES) to restore motor function, closed-loop feedback control may compensate for muscle fatigue, perturbations and nonlinearities in the behavior of the effected muscles. Kinematic state information is naturally represented in the firing rates of primary afferent neurons, which may be recorded with multi-electrode arrays at the level of the dorsal root ganglia (DRG). Previous work in cats has shown that it is feasible to estimate the kinematic state of the hind limb with a multivariate linear regression model of the neural activity in the DRG. In this study we extend these results to estimate the limb state in real-time during intramuscular stimulation in an anesthetized cat. Furthermore, we used the limb state estimates as feedback to a finite state FES controller to generate rudimentary walking behavior. This work demonstrates the feasibility of using DRG activity in a closed-loop FES system. PMID:22256011

  9. Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder

    PubMed Central

    Gao, Junling; Shi, Huqing; Wang, Xiang; Jiang, Yali; Ming, Qingsen; Gao, Yidian; Ma, Ren; Yao, Shuqiao

    2015-01-01

    Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum. PMID:26658732

  10. Neuropeptide Y in submucosal ganglia: regional differences in the innervation of guinea-pig large intestine.

    PubMed

    Cunningham, S M; Lees, G M

    1995-11-01

    Since information about possible regional differences in the innervation of the guinea-pig large intestine is incomplete, a comparative study was made of the occurrence of neurones and nerve fibres of the submucosa showing immunoreactivity (IR) to neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP). In addition, a quantitative analysis was made of submucosal neurones in regions of guinea-pig large intestine selected for probable differences in their function. There were two principal findings: First, the density of NPY-IR neurone somata was high in the ascending colon (mean +/- SEM 3148 +/- 464 neurones/cm2; n = 5 animals) and progressively declined in an anal direction, the descending colon having 348 +/- 125 neurones/cm2 (in the same 5 animals); immunoreactive cell bodies were rare in the rectum. The reduced density was also reflected in a fall in the number of NPY-IR neurones/ganglion from 3.0 +/- 0.3 in the ascending colon to 0.5 +/- 0.2 in the descending colon. Second, varicose NPY-IR intraganglionic fibres were a conspicuous feature of the duodenum, caecum, transverse colon, descending colon and rectum, but not of the ileum, ascending colon or distal spiral. Moreover, in the descending colon and rectum the fibres were arranged in a loose 'cobweb' structure around non-NPY-IR neurone somata; in the caecum, there was an apparent paucity of NPY-IR somata but the exceptionally dense intraganglionic varicose fibre network may have obscured NPY-IR somata. In all regions, fibre baskets were rare. In the ascending colon, only 25 +/- 5% of ganglia (compared to 92 +/- 2% of ganglia in the descending colon) showed any intraganglionic nerve fibres; furthermore, when they occurred, these were not of the 'cobweb' type but, rather, they gave the ganglia a speckled appearance. In very immature fetuses at a stage of development when no neuropeptide somata could be found in either the myenteric or submucosal plexuses, many NPY-IR nerve fibres were present in the submucosa with a distribution similar to that of adult guinea pigs. With respect to the density of VIP-IR neurones in the large intestine, there was only a 40% reduction in the number of neurones/cm2 from proximal to distal colon, in contrast to the corresponding 90% reduction in the density of NPY-IR neurones. The number of VIP-IR neurones/ganglion (6.4) and the proportion of ganglia with VIP-IR fibres (> 90%) were constant. It is concluded that the striking regional dissimilarities in (i) the occurrence of NPY-IR neurone somata and (ii) in the disposition of intraganglionic NPY-IR nerve fibres indicate potentially important regional differences in the functions of neuropeptide Y as an antisecretory peptide in the local regulation of chloride transport in the mucosa and as a modulator of ganglionic transmission, respectively. PMID:8801263

  11. Post-traumatic basal ganglia haemorrhage in a child with primary central nervous system lymphoma.

    PubMed

    Jankowski, Pawel P; Levy, Michael L; Crawford, John Ross

    2013-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare tumour of childhood with 15-20 cases reported yearly in North America. We present a case of a 13-year-old boy diagnosed with PCNSL who presented more than one-and-a-half years post-treatment with high dose cytosine arabinoside and methotrexate with a right-sided basal ganglia haemorrhage on MRI following a concussion while playing organised football against medical advice. There was no evidence of an underlying vascular malformation or recurrent disease by MRI, cerebrospinal fluid analysis or positron emission tomography computed tomography (PET-CT). However, 6 months post-injury he presented with asymptomatic disease recurrence of the frontal lobe. Our case reports an unusual MRI pattern of post-traumatic injury in a child previously treated for PCNSL that would support a recommendation for the avoidance of contact sports in this population. PMID:23904430

  12. Basal Ganglia Circuits Underlying the Pathophysiology of Levodopa-Induced Dyskinesia

    PubMed Central

    Barroso-Chinea, Pedro; Bezard, Erwan

    2010-01-01

    Involuntary movements or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Dyskinesia is, ultimately, experienced by the vast majority of the patients. Despite the importance of this problem, little was known about the cause of dyskinesia, a situation that has dramatically evolved in the last few years with a focus upon the molecular and signaling changes induced by chronic levodopa treatment. Departing from this, we here review the progress made in functional anatomy and neuroimaging that have had a tremendous impact on our understanding of the anatomo-functional organization of the basal ganglia in Parkinsonism and dyskinetic states, notably the demonstration that dyskinesia are linked to a pathological processing of limbic and cognitive information. PMID:20890450

  13. The basal ganglia is necessary for learning spectral, but not temporal, features of birdsong.

    PubMed

    Ali, Farhan; Otchy, Timothy M; Pehlevan, Cengiz; Fantana, Antoniu L; Burak, Yoram; Ölveczky, Bence P

    2013-10-16

    Executing a motor skill requires the brain to control which muscles to activate at what times. How these aspects of control-motor implementation and timing-are acquired, and whether the learning processes underlying them differ, is not well understood. To address this, we used a reinforcement learning paradigm to independently manipulate both spectral and temporal features of birdsong, a complex learned motor sequence, while recording and perturbing activity in underlying circuits. Our results uncovered a striking dissociation in how neural circuits underlie learning in the two domains. The basal ganglia was required for modifying spectral, but not temporal, structure. This functional dissociation extended to the descending motor pathway, where recordings from a premotor cortex analog nucleus reflected changes to temporal, but not spectral, structure. Our results reveal a strategy in which the nervous system employs different and largely independent circuits to learn distinct aspects of a motor skill. PMID:24075977

  14. The highs and lows of beta activity in cortico-basal ganglia loops.

    PubMed

    Brittain, John-Stuart; Sharott, Andrew; Brown, Peter

    2014-06-01

    Oscillatory activity in the beta (13-30 Hz) frequency band is widespread in cortico-basal ganglia circuits, and becomes prominent in Parkinson's disease (PD). Here we develop the hypothesis that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information-coding space and hence computational capacity. Task and context drive this dynamic gating, so that for each state there will be an optimal level of network synchrony, and levels lower or higher than this will impair behavioural performance. Thus, both the pathological exaggeration of synchrony, as observed in PD, and the ability of interventions like deep brain stimulation (DBS) to excessively suppress synchrony can potentially lead to impairments in behavioural performance. Indeed, under physiological conditions, the manipulation of computational capacity by beta activity may itself present a mechanism of action selection and maintenance. PMID:24890470

  15. Dopamine D2 receptors regulate the anatomical balance of basal ganglia circuitry

    PubMed Central

    Cazorla, Maxime; de Carvalho, Fernanda Delmondes; Chohan, Muhammad O.; Shegda, Mariya; Chuhma, Nao; Rayport, Stephen; Ahmari, Susanne E.; Moore, Holly; Kellendonk, Christoph

    2013-01-01

    Summary Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bi-directionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Remarkably, chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output, and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers. PMID:24411738

  16. FROM REINFORCEMENT LEARNING MODELS OF THE BASAL GANGLIA TO THE PATHOPHYSIOLOGY OF PSYCHIATRIC AND NEUROLOGICAL DISORDERS

    PubMed Central

    Maia, Tiago V.; Frank, Michael J.

    2013-01-01

    Over the last decade and a half, reinforcement learning models have fostered an increasingly sophisticated understanding of the functions of dopamine and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits. More recently, these models, and the insights that they afford, have started to be used to understand key aspects of several psychiatric and neurological disorders that involve disturbances of the dopaminergic system and CBGTC circuits. We review this approach and its existing and potential applications to Parkinson’s disease, Tourette’s syndrome, attention-deficit/hyperactivity disorder, addiction, schizophrenia, and preclinical animal models used to screen novel antipsychotic drugs. The approach’s proven explanatory and predictive power bodes well for the continued growth of computational psychiatry and computational neurology. PMID:21270784

  17. A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds

    PubMed Central

    Goldberg, Jesse H.

    2012-01-01

    The pallido-recipient thalamus transmits information from the basal ganglia (BG) to the cortex and plays a critical role motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the BG, but the role of non-pallidal inputs, such as excitatory inputs from cortex, is unclear. We have recorded simultaneously from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a BG-recipient thalamic nucleus necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone, and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor ‘cortical’ nucleus also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals important for exploratory behavior and learning. PMID:22327474

  18. New Roles for the External Globus Pallidus in Basal Ganglia Circuits and Behavior

    PubMed Central

    Berke, Joshua D.; Bevan, Mark D.; Chan, C. Savio; Mallet, Nicolas; Morrow, Michelle M.; Schmidt, Robert

    2014-01-01

    The development of methodology to identify specific cell populations and circuits within the basal ganglia is rapidly transforming our ability to understand the function of this complex circuit. This mini-symposium highlights recent advances in delineating the organization and function of neural circuits in the external segment of the globus pallidus (GPe). Although long considered a homogeneous structure in the motor-suppressing “indirect-pathway,” the GPe consists of a number of distinct cell types and anatomical subdomains that contribute differentially to both motor and nonmotor features of behavior. Here, we integrate recent studies using techniques, such as viral tracing, transgenic mice, electrophysiology, and behavioral approaches, to create a revised framework for understanding how the GPe relates to behavior in both health and disease. PMID:25392486

  19. Molecular heterogeneity of large-conductance calcium-activated potassium channels in canine intracardiac ganglia

    PubMed Central

    Selga, Elisabet; Pérez-Serra, Alexandra; Moreno-Asso, Alba; Anderson, Seth; Thomas, Kristen; Desai, Mayurika; Brugada, Ramon; Pérez, Guillermo J; Scornik, Fabiana S

    2013-01-01

    Large conductance calcium-activated potassium (BK) channels are widely expressed in the nervous system. We have recently shown that principal neurons from canine intracardiac ganglia (ICG) express a paxilline- and TEA-sensitive BK current, which increases neuronal excitability. In the present work, we further explore the molecular constituents of the BK current in canine ICG. We found that the ?1 and ?4 regulatory subunits are expressed in ICG. Single channel voltage-dependence at different calcium concentrations suggested that association of the BK? with a particular ? subunit was not enough to explain the channel activity in this tissue. Indeed, we detected the presence of several splice variants of the BK? subunit. In conclusion, BK channels in canine ICG may result from the arrangement of different BK? splice variants, plus accessory ? subunits. The particular combinations expressed in canine IC neurons likely rule the excitatory role of BK current in this tissue. PMID:23807090

  20. Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways.

    PubMed

    Martín, R; Bajo-Grañeras, R; Moratalla, R; Perea, G; Araque, A

    2015-08-14

    Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters and release gliotransmitters that modulate synaptic transmission. However, the cell- and synapse-specificity of the functional relationship between astrocytes and neurons in certain brain circuits remains unknown. In the dorsal striatum, which mainly comprises two intermingled subtypes (striatonigral and striatopallidal) of medium spiny neurons (MSNs) and synapses belonging to two neural circuits (the direct and indirect pathways of the basal ganglia), subpopulations of astrocytes selectively responded to specific MSN subtype activity. These subpopulations of astrocytes released glutamate that selectively activated N-methyl-d-aspartate receptors in homotypic, but not heterotypic, MSNs. Likewise, astrocyte subpopulations selectively regulated homotypic synapses through metabotropic glutamate receptor activation. Therefore, bidirectional astrocyte-neuron signaling selectively occurs between specific subpopulations of astrocytes, neurons, and synapses. PMID:26273054

  1. The basal ganglia is necessary for learning spectral, but not temporal features of birdsong

    PubMed Central

    Ali, Farhan; Fantana, Antoniu L.; Burak, Yoram; Ölveczky, Bence P.

    2013-01-01

    Executing a motor skill requires the brain to control which muscles to activate at what times. How these aspects of control - motor implementation and timing - are acquired, and whether the learning processes underlying them differ, is not well understood. To address this we used a reinforcement learning paradigm to independently manipulate both spectral and temporal features of birdsong, a complex learned motor sequence, while recording and perturbing activity in underlying circuits. Our results uncovered a striking dissociation in how neural circuits underlie learning in the two domains. The basal ganglia was required for modifying spectral, but not temporal structure. This functional dissociation extended to the descending motor pathway, where recordings from a premotor cortex analogue nucleus reflected changes to temporal, but not spectral structure. Our results reveal a strategy in which the nervous system employs different and largely independent circuits to learn distinct aspects of a motor skill. PMID:24075977

  2. Limb apraxia in patients with damage confined to the left basal ganglia and thalamus.

    PubMed Central

    De Renzi, E; Faglioni, P; Scarpa, M; Crisi, G

    1986-01-01

    Limb apraxia was investigated with standardised tests in 14 patients whose CT scan provided evidence of a vascular lesion confined to the left basal ganglia, or the thalamus, or both, and not involving the cortex or adjacent white matter. Five patients were severely impaired in imitating movements and pantomiming object use. Four of them also performed poorly when tested with real objects. In two patients the lesion was primarily thalamic and in three the lesion was primarily in the lenticular nucleus and the posterior limb of the internal capsule. Patients without apraxia generally had smaller injuries, but there were exceptions. Apraxia is currently conceived of as due to damage of cortical areas and their cortico-cortical connections, but the present data suggest that the model should be enlarged to include the deep nuclei and the pathways running through them. Images PMID:3760891

  3. [Consequences of lesions of the basal ganglia on cerebral metabolic activity: clinical implications].

    PubMed

    Baron, J C

    1994-01-01

    This brief overview summarises the literature regarding the effects of lesions of the basal ganglia (BG) on brain metabolism-an index of integrated synaptic activity. Interest in this field is because to show such effects may reveal the implication of neuron networks, damaged at the level of the BG, in the neuropsychological and behavioural expression of BG lesions. As an illustration of this, a parallel is drawn between the loss of psychic self-activation (also named "psychic akinesia" or "athymhormia") that follows bilateral lesions at variable sites of the prefrontal-striatal-pallidal-thalamic loop on one hand, and the mild prefrontal hypometabolism consistently observed in such cases. This paper also reviews the changes in brain metabolism found in progressive supranuclear palsy, Huntington's disease, Parkinson's disease, Wilson's disease and striato-nigral degeneration. PMID:7754297

  4. Structural differences in basal ganglia of elite running versus martial arts athletes: a diffusion tensor imaging study.

    PubMed

    Chang, Yu-Kai; Tsai, Jack Han-Chao; Wang, Chun-Chih; Chang, Erik Chihhung

    2015-07-01

    The aim of this study was to use diffusion tensor imaging (DTI) to characterize and compare microscopic differences in white matter integrity in the basal ganglia between elite professional athletes specializing in running and martial arts. Thirty-three young adults with sport-related skills as elite professional runners (n = 11) or elite professional martial artists (n = 11) were recruited and compared with non-athletic and healthy controls (n = 11). All participants underwent health- and skill-related physical fitness assessments. Fractional anisotropy (FA) and mean diffusivity (MD), the primary indices derived from DTI, were computed for five regions of interest in the bilateral basal ganglia, including the caudate nucleus, putamen, globus pallidus internal segment (GPi), globus pallidus external segment (GPe), and subthalamic nucleus. Results revealed that both athletic groups demonstrated better physical fitness indices compared with their control counterparts, with the running group exhibiting the highest cardiovascular fitness and the martial arts group exhibiting the highest muscular endurance and flexibility. With respect to the basal ganglia, both athletic groups showed significantly lower FA and marginally higher MD values in the GPi compared with the healthy control group. These findings suggest that professional sport or motor skill training is associated with changes in white matter integrity in specific regions of the basal ganglia, although these positive changes did not appear to depend on the type of sport-related motor skill being practiced. PMID:25929552

  5. Basal Ganglia Structures Differentially Contribute to Verbal Fluency: Evidence from Human Immunodeficiency Virus (HIV)-Infected Adults

    ERIC Educational Resources Information Center

    Thames, April D.; Foley, Jessica M.; Wright, Matthew J.; Panos, Stella E.; Ettenhofer, Mark; Ramezani, Amir; Streiff, Vanessa; El-Saden, Suzie; Goodwin, Scott; Bookheimer, Susan Y.; Hinkin, Charles H.

    2012-01-01

    Background: The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to…

  6. Distribution of FMRFamide-like immunoreactivity in the alimentary tract and hindgut ganglia of the barnacle Balanus amphitrite (Cirripedia, Crustacea).

    PubMed

    Gallus, Lorenzo; Bottaro, Massimiliano; Ferrando, Sara; Girosi, Laura; Ramoino, Paola; Tagliafierro, Grazia

    2006-08-01

    In this study, the presence and distribution of FMRFamide-like immunoreactivity in the alimentary tract of barnacle Balanus amphitrite were investigated. A net of nerve fibers strongly immunoreactive to FMRFamide-like molecules was localized in the posterior midgut and hindgut. Positive varicose nerve terminals were also localized close to the circular muscle cells and, in the hindgut, close to the radial muscular fibers. Besides this nerve fibers network, one pair of contralateral ganglia was localized in the hindgut, each of them constituted by two strongly FMRFamide-labeled neurons and one nonlabeled neuron. Their immunoreactive axons directed toward the hindgut and posterior midgut suggest an involvement of FMRFamide-like substances in adult B. amphitrite gut motility. The hindgut associated ganglia of barnacles seem to correspond to the terminal abdominal ganglia of the other crustaceans. Since they are the only residual gut ganglia in the barnacle's reduced nervous system, we can hypothesize that gut motility needs a nervous system regulation partially independent of the central nervous system. PMID:16770768

  7. [Adrenoreception characteristics of the neurons of the superior cervical and caudal mesenteric sympathetic ganglia of the cat].

    PubMed

    Komissarov, I V; Krivobok, G K

    1975-10-01

    Experiments were conducted on the supeior cervical and the caudal mesenteric sympathetic ganglia of a cat; it was shown that dophamine (DA), similarly to noradrenaline (NA) and adrenaline (A), depressed the cholinergic conduction. The activity of DA in the superior sympathetic ganglion was less than that of the NA and A 2- and 3-fold, respectively, and in the caudal mesenteric ganglia DA was 50 times more active than NA by the capacity to depress the cholinergic conduction. The effects of DA and NA in the superior cervical ganglia were eliminated by dyhydroergotamine, phentholamine and haloperidol, but not by tropaphen and chlorpormazine. In the caudal mesenteric ganglia the inhibitory effect of NA was decreased by phentholamine, dihydroergotamine and chlorpromazine, but not by haloperidol. On the contrary, haloperidol and chlorpromzine decreased the depressive effect of DA on the cholinergic conduction in the caudal mesenteric ganglion, whereas phentholamine, dihydroergotamine and deseryl proved to be ineffective. It is supposed that the manifestation of the dopaminergic mechanism of inhibition of cholinergic conduction in the caudal mesenteric sympathetic ganglion could underlie the dilatation of the mesenterial and renal vessels and its hypotensive action caused by DA. PMID:1227625

  8. Neuropeptides in the cerebral ganglia of the mud crab, Scylla paramamosain: transcriptomic analysis and expression profiles during vitellogenesis.

    PubMed

    Bao, Chenchang; Yang, Yanan; Huang, Huiyang; Ye, Haihui

    2015-01-01

    Neuropeptides play a critical role in regulating animal reproduction. In vertebrates, GnRH, GnIH and kisspeptin are the key neuropeptide hormones of the reproductive axis, however, the reproductive axis for invertebrates is vague. Knowledge on ovarian development of the mud crab, Scylla paramamosain, is critical for aquaculture and resources management of the commercially important species. This study employed Illumina sequencing, reverse transcription-polymerase chain reaction and quantitative real-time PCR techniques to identify neuropeptides that may be involved in ovarian development of S. paramamosain. A total of 32 neuropeptide transcripts from two dozen neuropeptide families, 100 distinct mature peptides were predicted from the transcriptome data of female S. paramamosain cerebral ganglia. Among them, two families, i.e. GSEFLamide and WXXXRamide, were first identified from the cerebral ganglia of crustaceans. Of these neuropeptides, 21 transcripts of interest were selected for further confirmation and all of them were detected in the cerebral ganglia, as well as in other nervous tissues and the ovary. Most of them also had differential expression in the cerebral ganglia during various vitellogenic stages, suggesting their likely involvement in regulating vitellogenesis and ovarian maturation. Overall, these findings provide an important basis for subsequent studies on peptide function in reproduction of S. paramamosain. PMID:26592767

  9. Neuropeptides in the cerebral ganglia of the mud crab, Scylla paramamosain: transcriptomic analysis and expression profiles during vitellogenesis

    PubMed Central

    Bao, Chenchang; Yang, Yanan; Huang, Huiyang; Ye, Haihui

    2015-01-01

    Neuropeptides play a critical role in regulating animal reproduction. In vertebrates, GnRH, GnIH and kisspeptin are the key neuropeptide hormones of the reproductive axis, however, the reproductive axis for invertebrates is vague. Knowledge on ovarian development of the mud crab, Scylla paramamosain, is critical for aquaculture and resources management of the commercially important species. This study employed Illumina sequencing, reverse transcription-polymerase chain reaction and quantitative real-time PCR techniques to identify neuropeptides that may be involved in ovarian development of S. paramamosain. A total of 32 neuropeptide transcripts from two dozen neuropeptide families, 100 distinct mature peptides were predicted from the transcriptome data of female S. paramamosain cerebral ganglia. Among them, two families, i.e. GSEFLamide and WXXXRamide, were first identified from the cerebral ganglia of crustaceans. Of these neuropeptides, 21 transcripts of interest were selected for further confirmation and all of them were detected in the cerebral ganglia, as well as in other nervous tissues and the ovary. Most of them also had differential expression in the cerebral ganglia during various vitellogenic stages, suggesting their likely involvement in regulating vitellogenesis and ovarian maturation. Overall, these findings provide an important basis for subsequent studies on peptide function in reproduction of S. paramamosain. PMID:26592767

  10. Localization of Molecular Correlates of Memory Consolidation to Buccal Ganglia Mechanoafferent Neurons after Learning that Food Is Inedible in "Aplysia"

    ERIC Educational Resources Information Center

    Levitan, David; Saada-Madar, Ravit; Teplinsky, Anastasiya; Susswein, Abraham J.

    2012-01-01

    Training paradigms affecting "Aplysia" withdrawal reflexes cause changes in gene expression leading to long-term memory formation in primary mechanoafferents that initiate withdrawal. Similar mechanoafferents are also found in the buccal ganglia that control feeding behavior, raising the possibility that these mechanoafferents are a locus of…

  11. Alternative exon splicing of cyclic AMP response element-binding protein in peripheral sensory and sympathetic ganglia of the rat.

    PubMed

    Pietruck, C; Xie, G X; Sharma, M; Meuser, T; Palmer, P P

    1999-01-01

    Alternative splicing patterns of cyclic AMP response element-binding protein (CREB) in dorsal root ganglia, lumbar sympathetic ganglia and several peripheral tissues of the rat have been investigated by an exon-flanking polymerase chain reaction strategy. A series of RT-PCR with primer pairs flanking all possible alternative splicing sites (corresponding to a genomic region with at least one full exon and two flanking introns) has revealed multiple tissue specific splice variants. These include some novel transcripts that lack the phosphorylation site and part of the leucine zipper region which is crucial for dimerization and DNA binding. Some isoforms previously reported as testis-specific were also detected in rat peripheral ganglia and other tissues. Notably, splicing patterns are specific for some regions. Some of the splice variants indicate inhibitory functions due to lacking phosphorylation sites or partially missing DNA-binding or leucine zipper domains. These findings suggest a complex expression and functional regulation of CREB in peripheral tissues including dorsal root and sympathetic ganglia. PMID:10576592

  12. Localization of Molecular Correlates of Memory Consolidation to Buccal Ganglia Mechanoafferent Neurons after Learning that Food Is Inedible in "Aplysia"

    ERIC Educational Resources Information Center

    Levitan, David; Saada-Madar, Ravit; Teplinsky, Anastasiya; Susswein, Abraham J.

    2012-01-01

    Training paradigms affecting "Aplysia" withdrawal reflexes cause changes in gene expression leading to long-term memory formation in primary mechanoafferents that initiate withdrawal. Similar mechanoafferents are also found in the buccal ganglia that control feeding behavior, raising the possibility that these mechanoafferents are a locus of…

  13. Basal Ganglia, Dopamine and Temporal Processing: Performance on Three Timing Tasks on and off Medication in Parkinson's Disease

    ERIC Educational Resources Information Center

    Jones, Catherine R. G.; Malone, Tim J. L.; Dirnberger, Georg; Edwards, Mark; Jahanshahi, Marjan

    2008-01-01

    A pervasive hypothesis in the timing literature is that temporal processing in the milliseconds and seconds range engages the basal ganglia and is modulated by dopamine. This hypothesis was investigated by testing 12 patients with Parkinson's disease (PD), both "on" and "off" dopaminergic medication, and 20 healthy controls on three timing tasks.…

  14. Immunocytochemical localization of neuropeptide Y, serotonin, substance P and ?-endorphin in optic ganglia and brain of Metapenaeus ensis

    NASA Astrophysics Data System (ADS)

    Ye, Haihui; Wang, Guizhong; Jin, Zhuxing; Huang, Huiyang; Li, Shaojing

    2006-12-01

    By using immunocytochemistry method of Strept Avidin-Biotin-Complex, four kinds of antisera raised against rabbits were applied to observe the immunoreactive neurons and neuropils of serotonin (5-HT), neuropeptide Y (NPY), substance P (SP) and ?-Endorphin (?-Ep) in optic ganglia and brain of Metapenaeus ensis. The results showed that, the 5-HT-immunoreactive cells were located in all the four neuropils of optic ganglia. Immunoreactivity of 5-HT was detected in anterior medial protocerebrum neuropils (AMPN), and the inner and outer lateral beside olfactory lobe (OL) of deutocerebrum. The presence of NPY-immunoreactive cells was found in all the four neuropils of the optic ganglia. NPY-immunoreactivity occurred in the anterior median cell cluster, lateral cell cluster of protocerebrum, and cell cluster beside OL and AMPN. SP-immunoreactivity was found in medulla terminalis (MT) of optic ganglia, and lateral cell cluster of protocerebrum and posterior lateral cell cluster of tritocerebrum. ?-Ep-immunoreactive cells were in MT only. In conclusion, these specific distribution patterns of the four immunoreactive substances can be used as morphological clues for understanding their different neurophysiological functions.

  15. SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia

    PubMed Central

    Baker, Matt; Strongosky, Audrey J.; Sanchez-Contreras, Monica Y.; Yang, Shan; Ferguson, Will; Calne, Donald B.; Calne, Susan; Stoessl, A. Jon; Allanson, Judith E.; Broderick, Daniel F.; Hutton, Michael L.; Dickson, Dennis W.; Ross, Owen A.; Wszolek, Zbigniew K.; Rademakers, Rosa

    2013-01-01

    Idiopathic Basal Ganglia Calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and Taqman copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in 2 of the 27 cases of IBGC (7%). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. Taqman copy-number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256 bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early-onset dystonia in this family. The identification of a SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated. PMID:24135862

  16. Using a hybrid neuron in physiologically inspired models of the basal ganglia.

    PubMed

    Thibeault, Corey M; Srinivasa, Narayan

    2013-01-01

    Our current understanding of the basal ganglia (BG) has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the BG, however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the BG, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation (DBS). The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under DBS. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of DBS and the latter allowing for the efficient simulation of larger more comprehensive networks. PMID:23847524

  17. Immunolocalization of serotonin in Onychophora argues against segmental ganglia being an ancestral feature of arthropods

    PubMed Central

    Mayer, Georg; Harzsch, Steffen

    2007-01-01

    Background Onychophora (velvet worms) represent the most basal arthropod group and play a pivotal role in the current discussion on the evolution of nervous systems and segmentation in arthropods. Although there is a wealth of information on the immunolocalization of serotonin (5-hydroxytryptamine, 5-HT) in various euarthropods, as yet no comparable localization data are available for Onychophora. In order to understand how the onychophoran nervous system compares to that of other arthropods, we studied the distribution of serotonin-like immunoreactive neurons and histological characteristics of ventral nerve cords in Metaperipatus blainvillei (Onychophora, Peripatopsidae) and Epiperipatus biolleyi (Onychophora, Peripatidae). Results We demonstrate that paired leg nerves are the only segmental structures associated with the onychophoran nerve cord. Although the median commissures and peripheral nerves show a repeated pattern, their arrangement is independent from body segments characterized by the position of legs and associated structures. Moreover, the somata of serotonin-like immunoreactive neurons do not show any ordered arrangement in both species studied but are instead scattered throughout the entire length of each nerve cord. We observed neither a serially iterated nor a bilaterally symmetric pattern, which is in contrast to the strictly segmental arrangement of serotonergic neurons in other arthropods. Conclusion Our histological findings and immunolocalization experiments highlight the medullary organization of the onychophoran nerve cord and argue against segmental ganglia of the typical euarthropodan type being an ancestral feature of Onychophora. These results contradict a priori assumptions of segmental ganglia being an ancestral feature of arthropods and, thus, weaken the traditional Articulata hypothesis, which proposes a sistergroup relationship of Annelida and Arthropoda. PMID:17629937

  18. Comparative Mapping of GABA-Immunoreactive Neurons in the Buccal Ganglia of Nudipleura Molluscs.

    PubMed

    Gunaratne, Charuni A; Katz, Paul S

    2016-04-15

    Phylogenetic comparisons of neurotransmitter distribution are important for understanding the ground plan organization of nervous systems. This study describes the γ-aminobutyric acid (GABA)-immunoreactive (GABA-ir) neurons in the buccal ganglia of six sea slug species (Mollusca, Gastropoda, Euthyneura, Nudipleura). In the nudibranch species, Hermissenda crassicornis, Tritonia diomedea, Tochuina tetraquetra, and Dendronotus iris, the number of GABA-ir neurons was highly consistent. Another nudibranch, Melibe leonina, however, contained approximately half the number of GABA-ir neurons. This may relate to its loss of a radula and its unique feeding behavior. The GABA immunoreactivity in a sister group to the nudibranchs, Pleurobranchaea californica, differed drastically from that of the nudibranchs. Not only did it have significantly more GABA-ir neurons but it also had a unique GABA distribution pattern. Furthermore, unlike the nudibranchs, the Pleurobranchaea GABA distribution was also different from that of other, more distantly related, euopisthobranch and panpulmonate snails and slugs. This suggests that the Pleurobranchaea GABA distribution may be a derived feature, unique to this lineage. The majority of GABA-ir axons and neuropil in the Nudipleura were restricted to the buccal ganglia, commissures, and connectives. However, in Tritonia and Pleurobranchaea, we detected a few GABA-ir fibers in buccal nerves that innervate feeding muscles. Although the specific functions of the GABA-ir neurons in the species in this study are not known, the innervation pattern suggests these neurons may play an integrative or regulatory role in bilaterally coordinated behaviors in the Nudipleura. J. Comp. Neurol. 524:1181-1192, 2016. © 2015 Wiley Periodicals, Inc. PMID:26355705

  19. SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia.

    PubMed

    Baker, Matt; Strongosky, Audrey J; Sanchez-Contreras, Monica Y; Yang, Shan; Ferguson, Will; Calne, Donald B; Calne, Susan; Stoessl, A Jon; Allanson, Judith E; Broderick, Daniel F; Hutton, Michael L; Dickson, Dennis W; Ross, Owen A; Wszolek, Zbigniew K; Rademakers, Rosa

    2014-03-01

    Idiopathic basal ganglia calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and TaqMan copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in two of the 27 cases of IBGC (7 %). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. TaqMan copy number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256-bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia-related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early onset dystonia in this family. The identification of an SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated. PMID:24135862

  20. Functional expression of TRPV1 and TRPA1 in rat vestibular ganglia.

    PubMed

    Kamakura, Takefumi; Ishida, Yusuke; Nakamura, Yukiko; Yamada, Takahiro; Kitahara, Tadashi; Takimoto, Yasumitsu; Horii, Arata; Uno, Atsuhiko; Imai, Takao; Okazaki, Suzuyo; Inohara, Hidenori; Shimada, Shoichi

    2013-09-27

    Both TRPV1 and TRPA1 are non-selective cation channels. They are co-expressed, and interact in sensory neurons such as dorsal root ganglia (DRG) and trigeminal ganglia (TG), and are involved in nociception, being activated by nociceptive stimuli. Immunohistological localization of TRPV1 in vestibular ganglion (VG) neurons has been reported. Although TRPA1 is co-expressed with TRPV1 in DRG and TG neurons, it is unclear whether TRPA1 channels are expressed in VG neurons. Moreover, it is unknown whether TRPV1 and TRPA1 channels are functional in VG neurons. We investigated the expression of TRPV1 and TRPA1 in rat VG neurons by RT-PCR, in situ hybridization, immunohistochemistry, and Ca(2+) imaging experiments. Both TRPV1 and TRPA1 RT-PCR products were amplified from the mRNA of rat VG neurons. In situ hybridization experiments showed TRPV1 and TRPA1 mRNA expression in the majority of VG neurons. Immunohistochemistry experiments confirmed TRPV1 protein expression. In Ca(2+) imaging experiments, capsaicin, a TRPV1 agonist, induced a significant increase in intracellular calcium ion concentration ([Ca(2+)]i) in rat primary cultured VG neurons, which was almost completely blocked by capsazepine, a TRPV1-specific antagonist. Cinnamaldehyde, a TRPA1 agonist, also caused an increase in [Ca(2+)]i, which was completely inhibited by HC030031, a TRPA1-specific antagonist. Moreover, in some VG neurons, a [Ca(2+)]i increase was evoked by both capsaicin and cinnamaldehyde in the same neuron. In summary, our histological and physiological studies reveal that TRPV1 and TRPA1 are expressed in VG neurons. It is suggested that TRPV1 and TRPA1 in VG neurons might participate in vestibular function and/or dysfunction such as vertigo. PMID:23916509

  1. From experimentation to the surgical treatment of Parkinson's disease: prelude or suite in basal ganglia research?

    PubMed

    Gross, C E; Boraud, T; Guehl, D; Bioulac, B; Bezard, E

    1999-12-01

    Parkinson's disease remains one of the greatest challenges facing those who work in the field of neurological research. Although the development of levodopa treatment revolutionised management of this debilitating diseases, no effective long-term therapy has yet been found. With recent advances in the understanding of basal ganglia physiopathology and the experimental demonstration of the efficacy of certain surgical procedures, there is a renewed interest in the surgical approach. This paper provides a chronological overview of the history of parkinsonian surgery and discusses the principal surgical options at our disposal today. These take three main forms: ablation (thalamotomy, pallidotomy and subthalamotomy); cell graft and gene therapy (mainly in the striatum); and deep brain stimulation (of the thalamus, globus pallidus pars internalis and the subthalamic nucleus). Our knowledge of basal ganglia function and our conception of how motor information is processed by this network have evolved parallel to the development of surgical techniques. Recent results from both clinical and experimental studies underline the complexity of the physiopathological mechanisms which generate parkinsonian symptomatology and lead us to question our assumption that each class of clinical signs (tremor, akinesia, rigidity, levodopa-induced dyskinesias...) is produced by a specific and separate mechanism. In the same way, comparison of the electrophysiological and biochemical effects of the different techniques induced in brain function vary considerably. This complex world of interaction and interconnection is a labyrinth that we are still far from comprehending in its entirety. All the more reason, in consequence, for extending experimental investigation into the impact of any new therapy before proposing its clinical application. PMID:10515666

  2. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

    PubMed Central

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

  3. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients

    PubMed Central

    Zhang, Xiaoyu; Ding, Lingling; Yang, Lei; Qin, Wei; Yuan, Junliang; Li, Shujuan; Hu, Wenli

    2016-01-01

    Background Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. Methods We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. Results During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. Conclusions Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia. PMID:26900696

  4. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

    PubMed

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

  5. Segmentation and Image Analysis of Abnormal Lungs at CT: Current Approaches, Challenges, and Future Trends.

    PubMed

    Mansoor, Awais; Bagci, Ulas; Foster, Brent; Xu, Ziyue; Papadakis, Georgios Z; Folio, Les R; Udupa, Jayaram K; Mollura, Daniel J

    2015-01-01

    The computer-based process of identifying the boundaries of lung from surrounding thoracic tissue on computed tomographic (CT) images, which is called segmentation, is a vital first step in radiologic pulmonary image analysis. Many algorithms and software platforms provide image segmentation routines for quantification of lung abnormalities; however, nearly all of the current image segmentation approaches apply well only if the lungs exhibit minimal or no pathologic conditions. When moderate to high amounts of disease or abnormalities with a challenging shape or appearance exist in the lungs, computer-aided detection systems may be highly likely to fail to depict those abnormal regions because of inaccurate segmentation methods. In particular, abnormalities such as pleural effusions, consolidations, and masses often cause inaccurate lung segmentation, which greatly limits the use of image processing methods in clinical and research contexts. In this review, a critical summary of the current methods for lung segmentation on CT images is provided, with special emphasis on the accuracy and performance of the methods in cases with abnormalities and cases with exemplary pathologic findings. The currently available segmentation methods can be divided into five major classes: (a) thresholding-based, (b) region-based, (c) shape-based, (d) neighboring anatomy-guided, and (e) machine learning-based methods. The feasibility of each class and its shortcomings are explained and illustrated with the most common lung abnormalities observed on CT images. In an overview, practical applications and evolving technologies combining the presented approaches for the practicing radiologist are detailed. PMID:26172351

  6. Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan

    PubMed Central

    Pujol, N.; Penadés, R.; Junqué, C.; Dinov, I.; Fu, C. H. Y.; Catalán, R.; Ibarretxe-Bilbao, N.; Bargalló, N.; Bernardo, M.; Toga, A.; Howard, R. J.; Costafreda, S. G.

    2014-01-01

    Background Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function. Aims To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function. Method Using 3 T magnetic resonance imaging we scanned 100 persons aged 19-82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape. Results There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group×age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function. Conclusions Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia. PMID:25213158

  7. Abnormal Web Usage Control by Proxy Strategies.

    ERIC Educational Resources Information Center

    Yu, Hsiang-Fu; Tseng, Li-Ming

    2002-01-01

    Approaches to designing a proxy server with Web usage control and to making the proxy server effective on local area networks are proposed to prevent abnormal Web access and to prioritize Web usage. A system is implemented to demonstrate the approaches. The implementation reveals that the proposed approaches are effective, such that the abnormal…

  8. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  9. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  10. An Abnormal Psychology Community Based Interview Assignment

    ERIC Educational Resources Information Center

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  11. Multiparametric tissue abnormality characterization using manifold regularization

    NASA Astrophysics Data System (ADS)

    Batmanghelich, Kayhan; Wu, Xiaoying; Zacharaki, Evangelia; Markowitz, Clyde E.; Davatzikos, Christos; Verma, Ragini

    2008-03-01

    Tissue abnormality characterization is a generalized segmentation problem which aims at determining a continuous score that can be assigned to the tissue which characterizes the extent of tissue deterioration, with completely healthy tissue being one end of the spectrum and fully abnormal tissue such as lesions, being on the other end. Our method is based on the assumptions that there is some tissue that is neither fully healthy or nor completely abnormal but lies in between the two in terms of abnormality; and that the voxel-wise score of tissue abnormality lies on a spatially and temporally smooth manifold of abnormality. Unlike in a pure classification problem which associates an independent label with each voxel without considering correlation with neighbors, or an absolute clustering problem which does not consider a priori knowledge of tissue type, we assume that diseased and healthy tissue lie on a manifold that encompasses the healthy tissue and diseased tissue, stretching from one to the other. We propose a semi-supervised method for determining such as abnormality manifold, using multi-parametric features incorporated into a support vector machine framework in combination with manifold regularization. We apply the framework towards the characterization of tissue abnormality to brains of multiple sclerosis patients.

  12. Ventilation abnormalities associated with pulmonary embolism

    SciTech Connect

    Sandler, M.S.; Velchik, M.G.; Alavi, A.

    1988-06-01

    A retrospective analysis of 2035 lung images performed over approximately 5 years revealed abnormal ventilation coexisting with pulmonary embolism in 18 patients. Matching ventilation perfusion defects may be associated with pulmonary embolism without infarction. In patients with a high clinical suspicion of acute pulmonary embolism and matching V/Q abnormalities, an angiogram may be necessary to definitely exclude the diagnosis.

  13. A new look at abnormal uterine bleeding.

    PubMed

    Twiss, Janice J

    2013-12-10

    New universal terminology, classifications, and definitions recommended by the International Federation of Gynecology and Obstetrics and supported by the American College of Obstetricians and Gynecologists to describe abnormal uterine bleeding abnormalities in reproductive women are presented. Identification and management of anovulatory and ovulatory uterine bleeding are explored. PMID:24177024

  14. Mapping abnormal subcortical brain morphometry in an elderly HIV + cohort

    PubMed Central

    Wade, Benjamin S.C.; Valcour, Victor G.; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Gutman, Boris A.; Thompson, Paul M.

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%. PMID:26640768

  15. FDG-PET evaluation of pleural abnormalities

    SciTech Connect

    Lowe, V.J.; Patz, E.; Harris, P.L.

    1994-05-01

    Pleural abnormalities identified on anatomical studies are often nonspecific and may represent benign or malignant disease. We prospectively evaluated the ability of FDG-PET to identify malignancy in patients with pleural abnormalities detected on chest radiographs or chest CT. Thirty-two patients with pleural abnormalities (pleural masses, thickening or effusions) found on chest radiographs or CT were evaluated by FDG-PET. Regions of interest (ROI) were identified on the PET images correlating to anatomic abnormalities and standard uptake ratios (SUR`s) of these ROI`s were calculated. A SUR value of 2.5 or greater was considered positive for malignancy. Physicians blinded to biopsy results graded their confidence of malignancy (1-5 scale) and graded lesion FDG uptake with respect to mediastinal radioactivity. Twenty-three of the patients had definitive diagnoses by tissue biopsy. Seventeen of these patients had malignant (SUR=7.9{plus_minus}3.8) and 6 had benign (SUR=2.8{plus_minus}2.4) causes of their pleural abnormalities (p=0.001). All but two malignant cases had SURs higher than 2.5 and one of these two was correctly interpreted by the observers. SURs lower than 2.5 were seen in four of the six (67%) benign pleural abnormalities. Using a combination of both visual and semiquantitative analysis, the sensitivity of FDG-PET for detecting malignant pleural abnormalities was 94%. Active infections in the pleural space had increased FDG uptake on PET studies while other benign pleural abnormalities did not. FDG-PET has very high sensitivity for detecting malignant pleural abnormalities and can differentiate benign from malignant pleural abnormalities.

  16. Shape-Shifting Plastic

    SciTech Connect

    2015-05-20

    A new plastic developed by ORNL and Washington State University transforms from its original shape through a series of temporary shapes and returns to its initial form. The shape-shifting process is controlled through changes in temperature

  17. Clinical and pathologic findings in two draft horses with progressive muscle atrophy, neuromuscular weakness, and abnormal gait characteristic of shivers syndrome.

    PubMed

    Valentine, B A; de Lahunta, A; Divers, T J; Ducharme, N G; Orcutt, R S

    1999-12-01

    Two Belgian geldings, 4 and 14 years old, respectively, with muscle atrophy, weakness, and abnormal gait characteristic of severe advanced shivers were examined clinically and on necropsy. Neurologic examination revealed no evidence of ataxia, and the clinical diagnosis was neuromuscular weakness and shivers. Necropsies of both horses, including examination of pituitary, brain, spinal cord, spinal roots and ganglia, and peripheral nerves, revealed no gross or histologic abnormalities. Examination of multiple skeletal muscle specimens revealed chronic myopathic changes and periodic acid-Schiff positive, amylase-resistant inclusions within muscle fibers, characteristic of equine polysaccharide storage myopathy. It is suggested that underlying metabolic myopathy may be the cause of muscle weakness and cramping in horses with shivers. PMID:14567431

  18. Rare cytogenetic abnormalities in myelodysplastic syndromes.

    PubMed

    Bacher, Ulrike; Schanz, Julie; Braulke, Friederike; Haase, Detlef

    2015-01-01

    The karyotype represents one of the main cornerstones for the International Prognostic Scoring System (IPSS) and the revised IPSS-R (IPSS-R) that are most widely used for prognostication in patients with myelodysplastic syndromes (MDS). The most frequent cytogenetic abnormalities in MDS, i.e. del(5q), -7/del(7q), +8, complex karyotypes, or -Y have been extensively explored for their prognostic impact. The IPSS-R also considers some less frequent abnormalities such as del(11q), isochromosome 17, +19, or 3q abnormalities. However, more than 600 different cytogenetic categories had been identified in a previous MDS study. This review aims to focus interest on selected rare cytogenetic abnormalities in patients with MDS. Examples are numerical gains of the chromosomes 11 (indicating rapid progression), of chromosome 14 or 14q (prognostically intermediate to favorable), -X (in females, with an intermediate prognosis), or numerical abnormalities of chromosome 21. Structural abnormalities are also considered, e.g. del(13q) that is associated with bone marrow failure syndromes and favorable response to immunosuppressive therapy. These and other rare cytogenetic abnormalities should be integrated into existing prognostication systems such as the IPSS-R. However, due to the very low number of cases, this is clearly dependent on international collaboration. Hopefully, this article will help to inaugurate this process. PMID:25960862

  19. Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats.

    PubMed

    Bai, Liying; Wang, Xinru; Li, Zhisong; Kong, Cunlong; Zhao, Yonghui; Qian, Jun-Liang; Kan, Quancheng; Zhang, Wei; Xu, Ji-Tian

    2016-02-01

    Emerging evidence indicates that CXCL12/CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mechanism. Here, we determined that spared nerve injury (SNI) increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia (DRG) neurons and satellite glial cells. SNI also induced long-lasting upregulation of CXCL12 and CXCR4 in the ipsilateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNI-induced a sustained increase in TNF-? expression in the DRG and spinal cord. Intraperitoneal injection (i.p.) of the TNF-? synthesis inhibitor thalidomide reduced the SNI-induced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection (i.t.) of the CXCR4 antagonist AMD3100, both 30 min before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. administration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the activation of ERK in the spinal cord. The mechanical hypersensitivity induced in naïve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-? might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL12/CXCR4 signaling via ERK activation contributes to the development and maintenance of neuropathic pain. PMID:26781879

  20. Numerically abnormal chromosome constitutions in humans

    SciTech Connect

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  1. Oculomotor abnormalities in schizophrenia: a critical review.

    PubMed

    Hutton, S; Kennard, C

    1998-03-01

    Oculomotor abnormalities, particularly in smooth pursuit tracking, are one of the most widely investigated biological markers of schizophrenia. However, despite the wealth of published data, important questions concerning the exact nature of these abnormalities remain unanswered. Many of the studies use unreliable methodology, and few attempts have been made to interpret the observed oculomotor dysfunction in terms of current understanding of eye movement physiology. Also, the potential effects of antipsychotic medication have been poorly addressed. Recent research, using more reliable measurement techniques and novel saccadic paradigms are producing important results and may provide a more productive framework for future studies of oculomotor abnormalities in schizophrenia. PMID:9521243

  2. Right Liver Lobe Hypoplasia and Related Abnormalities

    PubMed Central

    Alicioglu, Banu

    2015-01-01

    Summary Background Hypoplasia and agenesis of the liver lobe is a rare abnormality. It is associated with biliary system abnormalities, high location of the right kidney, and right colon interposition. These patients are prone to gallstones, portal hypertension and possible surgical complications because of anatomical disturbance. Case Report Magnetic resonance imaging features of a rare case of hypoplasia of the right lobe of the liver in a sigmoid cancer patient are presented. Conclusions Hypoplasia of the right liver should not be confused with liver atrophy; indeed, associations with other coexistent abnormalities are also possible. Awareness and familiarity with these anomalies are necessary to avoid fatal surgical and interventional complications. PMID:26634012

  3. Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

    SciTech Connect

    Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

    2009-03-09

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  4. Selective neuronal staining in tardigrades and onychophorans provides insights into the evolution of segmental ganglia in panarthropods

    PubMed Central

    2013-01-01

    Background Although molecular analyses have contributed to a better resolution of the animal tree of life, the phylogenetic position of tardigrades (water bears) is still controversial, as they have been united alternatively with nematodes, arthropods, onychophorans (velvet worms), or onychophorans plus arthropods. Depending on the hypothesis favoured, segmental ganglia in tardigrades and arthropods might either have evolved independently, or they might well be homologous, suggesting that they were either lost in onychophorans or are a synapomorphy of tardigrades and arthropods. To evaluate these alternatives, we analysed the organisation of the nervous system in three tardigrade species using antisera directed against tyrosinated and acetylated tubulin, the amine transmitter serotonin, and the invertebrate neuropeptides FMRFamide, allatostatin and perisulfakinin. In addition, we performed retrograde staining of nerves in the onychophoran Euperipatoides rowelli in order to compare the serial locations of motor neurons within the nervous system relative to the appendages they serve in arthropods, tardigrades and onychophorans. Results Contrary to a previous report from a Macrobiotus species, our immunocytochemical and electron microscopic data revealed contralateral fibres and bundles of neurites in each trunk ganglion of three tardigrade species, including Macrobiotus cf. harmsworthi, Paramacrobiotus richtersi and Hypsibius dujardini. Moreover, we identified additional, extra-ganglionic commissures in the interpedal regions bridging the paired longitudinal connectives. Within the ganglia we found serially repeated sets of serotonin- and RFamid-like immunoreactive neurons. Furthermore, our data show that the trunk ganglia of tardigrades, which include the somata of motor neurons, are shifted anteriorly with respect to each corresponding leg pair, whereas no such shift is evident in the arrangement of motor neurons in the onychophoran nerve cords. Conclusions Taken together, these data reveal three major correspondences between the segmental ganglia of tardigrades and arthropods, including (i) contralateral projections and commissures in each ganglion, (ii) segmentally repeated sets of immunoreactive neurons, and (iii) an anteriorly shifted (parasegmental) position of ganglia. These correspondences support the homology of segmental ganglia in tardigrades and arthropods, suggesting that these structures were either lost in Onychophora or, alternatively, evolved in the tardigrade/arthropod lineage. PMID:24152256

  5. Inhibition of neurally-evoked transmitter release by calcium channel antagonists in rat parasympathetic ganglia.

    PubMed Central

    Seabrook, G. R.; Adams, D. J.

    1989-01-01

    1. Excitatory postsynaptic potentials (e.p.s.ps) were recorded from the submandibular parasympathetic ganglia of newborn rats (10-20 days old), by intracellular microelectrode recording and a suction electrode to deliver stimulus trains to the lingual nerve (15 stimuli at 0.1, 0.3, 1, 3, and 10 Hz, 22 degrees C). Only evoked responses without voltage-dependent action potentials were analyzed (observed at membrane potentials negative to -70 mV), and e.p.s.p. amplitudes were determined for the plateau responses during each train (5-15th response). 2. Cadmium, an inorganic calcium channel antagonist, reduced e.p.s.p. amplitudes in a dose-dependent manner (Kd 74 microM, P less than 0.01). Nickel (1-300 microM) did not attenuate the amplitude of evoked responses. 3. Verapamil (0.1-30 microM), a phenylamine, had no significant effects upon e.p.s.p. amplitudes at any frequency examined. Higher concentrations of verapamil (100 microM) blocked neurally evoked responses in a manner consistent with the antagonism of voltage-sensitive sodium currents. 4. Diltiazem, a benzothiazepine, reduced e.p.s.p. amplitudes in a dose-dependent manner, the depression being accentuated at high stimulation frequencies (80% block at 30 microM and 10 Hz). The pure (-)-cis enantiomer of diltiazem (10-30 microM) was without effect. 5. Amlodipine, a 1,4-dihydropyridine, did not antagonize synaptic transmission at any stimulus frequency examined (10-30 microM, 0.1-10 Hz, n = 3). 6. Amiloride, a potassium-sparing diuretic, depressed the amplitudes of evoked responses in a dose-dependent manner (one-site Kd 31 microM, P less than 0.005), although the extent of the block was alleviated with high stimulus frequencies. The effects of 30 microM amiloride were unlikely to be of post-synaptic origin as both the amplitudes of miniature e.p.s.ps, and the iontophoretic potentials induced by exogenous acetylcholine, were not attenuated by treatment with this compound. The amiloride derivative, 3',4'-dichlorobenzamil was ineffective in reducing the amplitude of e.p.s.ps (30-100 microM). 7. omega-Conotoxin GVIA, a marine neurotoxin, which depressed whole cell calcium currents recorded from cultured rat parasympathetic cardiac neurones (up to 90% block at 10 nM), was ineffective at blocking synaptic transmission in submandibular ganglia (0.1-1 microM). 8. The differential effects of these calcium channel antagonists upon synaptic transmission in rat parasympathetic ganglia, suggest that either more than one type of calcium channel may be involved in transmitter release, or that the presynaptic calcium channels possess pharmacological sensitivities different from those of channel types described in ne PMID:2571381

  6. Abnormal intestinal permeability in Crohn's disease pathogenesis.

    PubMed

    Teshima, Christopher W; Dieleman, Levinus A; Meddings, Jon B

    2012-07-01

    Increased small intestinal permeability is a longstanding observation in both Crohn's disease patients and in their healthy, asymptomatic first-degree relatives. However, the significance of this compromised gut barrier function and its place in the pathogenesis of the disease remains poorly understood. The association between abnormal small intestinal permeability and a specific mutation in the NOD2 gene, which functions to modulate both innate and adaptive immune responses to intestinal bacteria, suggests a common, genetically determined pathway by which an abnormal gut barrier could result in chronic intestinal inflammation. Furthermore, rodent colitis models show that gut barrier defects precede the development of inflammatory changes. However, it remains possible that abnormal permeability is simply a consequence of mucosal inflammation. Further insight into whether abnormal barrier function is the cause or consequence of chronic intestinal inflammation will be crucial to understanding the role of intestinal permeability in the pathogenesis of Crohn's disease. PMID:22731729

  7. Abnormal Glycoprotein Antibodies Possible Detection Biomarkers

    Cancer.gov

    Scientists have found that cancer patients produce antibodies that target abnormal glycoproteins (proteins with sugar molecules attached) made by their tumors. The result of this work suggests that antitumor antibodies in the blood may provide a fruitful

  8. Damage characterization in plates using singularity of scale mode shapes

    NASA Astrophysics Data System (ADS)

    Cao, M. S.; Xu, H.; Bai, R. B.; Ostachowicz, W.; Radzie?ski, M.; Chen, L.

    2015-03-01

    Damage is a prevailing physical phenomenon in in-service structures; accumulation of damage can cause catastrophic structural failure. For damage identification in plates, the concept of scale mode shape with fractal singularity is formulated based on 2D Gabor wavelet transform incorporating fractal dimension analysis of measured mode shapes. With this concept, a scale fractal complexity spectrum is created to reveal mode shape singularities by eliminating noise and interference. The singularity manifests the abnormality of the mode shape, clearly indicating damage. This study develops a philosophy of fusing wavelets and fractals to detect singularities of physical fields in noisy conditions.

  9. Structural characteristics of the recognition site for cholinergic ligands in the nicotinic acetylcholine receptor from squid optical ganglia

    SciTech Connect

    Plyashkevich, Yu.G.; Demushkin, V.P.

    1986-01-20

    The influence of chemical modification on the parameters of the binding of cholinergic ligands by the nicotinic acetylcholine receptor of squid optical ganglia was investigated. The presence of two subpopulations of recognition sites, differing in the composition of the groups contained in them, was detected. It was established with high probability that subpopulation I contains arginine and tyrosine residues and a carboxyl group while subpopulation II contains an amino group, a thyrosine residue, and a carboxyl group. Moreover, in both subpopulations there is an amino group important only for the binding of tubocurarin. On the basis of the results obtained, a model of the recognition sites for cholinergic ligands of the nicotinic acetylcholine receptor of squid optical ganglia is proposed.

  10. Shape memory polymers

    DOEpatents

    Wilson, Thomas S.; Bearinger, Jane P.

    2015-06-09

    New shape memory polymer compositions, methods for synthesizing new shape memory polymers, and apparatus comprising an actuator and a shape memory polymer wherein the shape memory polymer comprises at least a portion of the actuator. A shape memory polymer comprising a polymer composition which physically forms a network structure wherein the polymer composition has shape-memory behavior and can be formed into a permanent primary shape, re-formed into a stable secondary shape, and controllably actuated to recover the permanent primary shape. Polymers have optimal aliphatic network structures due to minimization of dangling chains by using monomers that are symmetrical and that have matching amine and hydroxyl groups providing polymers and polymer foams with clarity, tight (narrow temperature range) single transitions, and high shape recovery and recovery force that are especially useful for implanting in the human body.

  11. Indirection and symbol-like processing in the prefrontal cortex and basal ganglia

    PubMed Central

    Kriete, Trenton; Noelle, David C.; Cohen, Jonathan D.; O’Reilly, Randall C.

    2013-01-01

    The ability to flexibly, rapidly, and accurately perform novel tasks is a hallmark of human behavior. In our everyday lives we are often faced with arbitrary instructions that we must understand and follow, and we are able to do so with remarkable ease. It has frequently been argued that this ability relies on symbol processing, which depends critically on the ability to represent variables and bind them to arbitrary values. Whereas symbol processing is a fundamental feature of all computer systems, it remains a mystery whether and how this ability is carried out by the brain. Here, we provide an example of how the structure and functioning of the prefrontal cortex/basal ganglia working memory system can support variable binding, through a form of indirection (akin to a pointer in computer science). We show how indirection enables the system to flexibly generalize its behavior substantially beyond its direct experience (i.e., systematicity). We argue that this provides a biologically plausible mechanism that approximates a key component of symbol processing, exhibiting both the flexibility, but also some of the limitations, that are associated with this ability in humans. PMID:24062434

  12. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection

    PubMed Central

    Baston, Chiara; Ursino, Mauro

    2015-01-01

    The basal ganglia (BG) are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go), indirect (NoGo), and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves) during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges), synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication). Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments. PMID:26640481

  13. Electrical stimulation reveals complex neuronal input and activation patterns in single myenteric guinea pig ganglia.

    PubMed

    Bisschops, R; Vanden Berghe, P; Bellon, E; Janssens, J; Tack, J

    2003-06-01

    The myenteric plexus plays a key role in the control of gastrointestinal motility. We used confocal calcium imaging to study responses to electrical train stimulation (ETS) of interganglionic fiber tracts in entire myenteric ganglia of the guinea pig small intestine. ETS induced calcium transients in a subset of neurons: 52.2% responded to oral ETS, 65.4% to aboral ETS, and 71.7% to simultaneous oral and aboral ETS. A total of 41.3% of the neurons displayed convergence of oral and aboral ETS-induced responses. Responses could be reversibly blocked with TTX (10(-)6 M), demonstrating involvement of neuronal conduction, and by removal of extracellular calcium. omega-Conotoxin (5 x 10(-7) M) blocked the majority of responses and reduced the amplitude of residual responses by 45%, indicating the involvement of N-type calcium channels. Staining for calbindin and calretinin did not reveal different response patterns in these immunohistochemically identified neurons. We conclude that, at least for ETS close to a ganglion, confocal calcium imaging reveals complex oral and aboral input to individual myenteric neurons rather than a polarization in spread of activity. PMID:12736152

  14. Idiopathic basal ganglia calcification-associated PDGFRB mutations impair the receptor signalling

    PubMed Central

    Arts, Florence A; Velghe, Amélie I; Stevens, Monique; Renauld, Jean-Christophe; Essaghir, Ahmed; Demoulin, Jean-Baptiste

    2015-01-01

    Platelet-derived growth factors (PDGF) bind to two related receptor tyrosine kinases, which are encoded by the PDGFRA and PDGFRB genes. Recently, heterozygous PDGFRB mutations have been described in patients diagnosed with idiopathic basal ganglia calcification (IBGC or Fahr disease), a rare inherited neurological disorder. The goal of the present study was to determine whether these mutations had a positive or negative impact on the PDGFRB activity. We first showed that the E1071V mutant behaved like wild-type PDGFRB and may represent a polymorphism unrelated to IBGC. In contrast, the L658P mutant had no kinase activity and failed to activate any of the pathways normally stimulated by PDGF. The R987W mutant activated Akt and MAP kinases but did not induce the phosphorylation of signal transducer and activator of transcription 3 (STAT3) after PDGF stimulation. Phosphorylation of phospholipase C? was also decreased. Finally, we showed that the R987W mutant was more rapidly degraded upon PDGF binding compared to wild-type PDGFRB. In conclusion, PDGFRB mutations associated with IBGC impair the receptor signalling. PDGFRB loss of function in IBGC is consistent with recently described inactivating mutations in the PDGF-B ligand. These results raise concerns about the long-term safety of PDGF receptor inhibition by drugs such as imatinib. PMID:25292412

  15. Idiopathic basal ganglia calcification-associated PDGFRB mutations impair the receptor signalling.

    PubMed

    Arts, Florence A; Velghe, Amélie I; Stevens, Monique; Renauld, Jean-Christophe; Essaghir, Ahmed; Demoulin, Jean-Baptiste

    2015-01-01

    Platelet-derived growth factors (PDGF) bind to two related receptor tyrosine kinases, which are encoded by the PDGFRA and PDGFRB genes. Recently, heterozygous PDGFRB mutations have been described in patients diagnosed with idiopathic basal ganglia calcification (IBGC or Fahr disease), a rare inherited neurological disorder. The goal of the present study was to determine whether these mutations had a positive or negative impact on the PDGFRB activity. We first showed that the E1071V mutant behaved like wild-type PDGFRB and may represent a polymorphism unrelated to IBGC. In contrast, the L658P mutant had no kinase activity and failed to activate any of the pathways normally stimulated by PDGF. The R987W mutant activated Akt and MAP kinases but did not induce the phosphorylation of signal transducer and activator of transcription 3 (STAT3) after PDGF stimulation. Phosphorylation of phospholipase C? was also decreased. Finally, we showed that the R987W mutant was more rapidly degraded upon PDGF binding compared to wild-type PDGFRB. In conclusion, PDGFRB mutations associated with IBGC impair the receptor signalling. PDGFRB loss of function in IBGC is consistent with recently described inactivating mutations in the PDGF-B ligand. These results raise concerns about the long-term safety of PDGF receptor inhibition by drugs such as imatinib. PMID:25292412

  16. Novel SLC20A2 mutations identified in southern Chinese patients with idiopathic basal ganglia calcification.

    PubMed

    Chen, Wan-Jin; Yao, Xiang-Ping; Zhang, Qi-Jie; Ni, Wang; He, Jin; Li, Hong-Fu; Liu, Xin-Yi; Zhao, Gui-Xian; Murong, Shen-Xing; Wang, Ning; Wu, Zhi-Ying

    2013-10-15

    Idiopathic basal ganglia calcification (IBGC) is a rare neuropsychiatric disorder characterized by bilateral and symmetric cerebral calcifications. Recently, SLC20A2 was identified as a causative gene for familial IBGC, and three mutations were reported in a northern Chinese population. Here, we aimed to explore the mutation spectrum of SLC20A2 in a southern Chinese population. Sanger sequencing was employed to screen mutations within SLC20A2 in two IBGC families and 14 sporadic IBGC cases from a southern Han Chinese population. Four novel mutations (c.82G>A p.D28N, c.185T>C p.L62P, c.1470_1478delGCAGGTCCT p.Q491_L493del and c.935-1G>A) were identified in two families and two sporadic cases, respectively; none were detected in 200 unrelated controls. No mutation was found in the remaining 12 patients. Different mutations may result in varied phenotypes, including brain calcification and clinical manifestations. Our study supports the hypothesis that SLC20A2 is a causative gene of IBGC and expands the mutation spectrum of SLC20A2, which facilitates the understanding of the genotype-phenotype correlation of IBGC. PMID:23939468

  17. Real-time control of walking using recordings from dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Holinski, B. J.; Everaert, D. G.; Mushahwar, V. K.; Stein, R. B.

    2013-10-01

    Objective. The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach. In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the DRG. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modelled from recorded neural firing rates. These models were then used for closed-loop feedback. Main results. Overall, firing-rate-based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48 ± 13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance. Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development.

  18. The transcriptional landscape of dorsal root ganglia after sciatic nerve transection

    PubMed Central

    Li, Shiying; Xue, Chengbin; Yuan, Ying; Zhang, Ruirui; Wang, Yaxian; Wang, Yongjun; Yu, Bin; Liu, Jie; Ding, Fei; Yang, Yuming; Gu, Xiaosong

    2015-01-01

    Following peripheral nerve injury, transcriptional responses are orchestrated to regulate the expression of numerous genes in the lesioned nerve, thus activating the intrinsic regeneration program. To better understand the molecular regulation of peripheral nerve regeneration, we aimed at investigating the transcriptional landscape of dorsal root ganglia (DRGs) after sciatic nerve transection in rats. The cDNA microarray analysis was used to identify thousands of genes that were differentially expressed at different time points post nerve injury (PNI). The results from Euclidean distance matrix, principal component analysis, and hierarchical clustering indicated that 2 nodal transitions in temporal gene expressions could segregate 3 distinct transcriptional phases within the period of 14 d PNI. The 3 phases were designated as “a stress response phase”, “a pre-regeneration phase”, and “a regeneration phase”, respectively, by referring to morphological observation of post-nerve-injury changes. The gene ontology (GO) analysis revealed the distinct features of biological process, cellular component, and molecular function at each transcriptional phase. Moreover, Ingenuity Pathway Analysis suggested that differentially expressed genes, mainly transcription factors and genes associated with neurite/axon growth, might be integrated into regulatory networks to mediate the regulation of peripheral nerve regeneration in a highly cooperative manner. PMID:26576491

  19. Expression pattern of leucine-rich repeat neuronal protein 4 in adult mouse dorsal root ganglia.

    PubMed

    Bando, Takayoshi; Morikawa, Yoshihiro; Hisaoka, Tomoko; Komori, Tadasuke; Miyajima, Atsushi; Senba, Emiko

    2012-11-30

    A member of leucine-rich repeat neuronal protein family, leucine-rich repeat neuronal protein 4 (Lrrn4), is a type I transmembrane protein. Previously, we have reported that Lrrn4 is expressed in various regions of the central nervous system (CNS) and involved in the memory retention. However, little is known about the role of Lrrn4 in the peripheral nervous system (PNS). Northern blot analysis revealed that Lrrn4 mRNA was expressed predominantly in the dorsal root ganglia (DRGs) with low levels in some regions of the CNS. To identify Lrrn4-expressing cells in the DRGs, we performed in situ hybridization histochemistry and LacZ staining in Lrrn4-heterozygous (Lrrn4+/-) mice generated by the replacement of Lrrn4 gene with ?-galactosidase gene. In the adult DRGs, 8% of total DRG neurons contained Lrrn4 mRNA, which was exclusively expressed in the small-sized neurons. LacZ staining combined with immunohistochemistry revealed that approximately 42% and 58% of Lrrn4-positive neurons contained receptor tyrosine kinase A (TrkA)- and Ret-immunoreactivity, respectively. After sciatic nerve axotomy, the expression of Lrrn4 mRNA was reduced in injured side of the DRGs. Thus, Lrrn4 is expressed in a subset of nociceptive neurons and might contribute to the maintenance of nociceptive circuits. PMID:23069668

  20. Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

    PubMed Central

    Ellens, Damien J.; Leventhal, Daniel K.

    2014-01-01

    Incomplete understanding of the systems-level pathophysiology of Parkinson Disease (PD) remains a significant barrier to improving its treatment. Substantial progress has been made, however, due to the availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons. This review discusses the in vivo electrophysiology of basal ganglia (BG), thalamic, and cortical regions after dopamine-depleting lesions. These include firing rate changes, neuronal burst-firing, neuronal oscillations, and neuronal synchrony that result from a combination of local microanatomic changes and network-level interactions. While much is known of the clinical and electrophysiological phenomenology of dopamine loss, a critical gap in our conception of PD pathophysiology is the link between them. We discuss potential mechanisms by which these systems-level electrophysiological changes may emerge, as well as how they may relate to clinical parkinsonism. Proposals for an updated understanding of BG function are reviewed, with an emphasis on how emerging frameworks will guide future research into the pathophysiology and treatment of PD. PMID:23948994

  1. Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training

    PubMed Central

    Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-01-01

    Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training. PMID:26035693

  2. Dopamine physiology in the basal ganglia of male zebra finches during social stimulation

    PubMed Central

    Ihle, Eva C; van der Hart, Marieke; Jongsma, Minke; Tecott, Larry H; Doupe, Allison J

    2015-01-01

    Accumulating evidence suggests that dopamine (DA) is involved in altering neural activity and gene expression in a zebra finch cortical–basal ganglia circuit specialized for singing, upon the shift between solitary singing and singing as a part of courtship. Our objective here was to sample changes in the extracellular concentrations of DA in Area X of adult and juvenile birds, to test the hypothesis that DA levels would change similarly during presentation of a socially salient stimulus in both age groups. We used microdialysis to sample the extracellular milieu of Area X in awake, behaving adult and juvenile male zebra finches, and analysed the dialysate using high-performance liquid chromatography coupled with electrochemical detection. The extracellular levels of DA in Area X increased significantly during both female presentation to adult males and tutor presentation to juvenile males. DA levels were not correlated with the time spent singing. We also reverse-dialysed Area X with pharmacologic agents that act either on DA systems directly or on norepinephrine, and found that all of these agents significantly increased DA levels (3- to 10-fold) in Area X. These findings suggest that changes in extracellular DA levels can be stimulated similarly by very different social contexts (courtship and interaction with tutor), and influenced potently by dopaminergic and noradrenergic drugs. These results raise the possibility that the arousal level or attentional state of the subject (rather than singing behavior) is the common feature eliciting changes in extracellular DA concentration. PMID:25872575

  3. A direct GABAergic output from the basal ganglia to frontal cortex

    PubMed Central

    Saunders, Arpiar; Oldenburg, Ian A.; Berezovskii, Vladimir K.; Johnson, Caroline A.; Kingery, Nathan D.; Elliott, Hunter L.; Xie, Tiao; Gerfen, Charles R.; Sabatini, Bernardo L.

    2014-01-01

    The basal ganglia (BG) are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning1. Current models postulate that the BG modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by the BG via direct (dSPNs) and indirect (iSPNs) pathway striatal projection neurons2–4. The BG thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems5. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT+ cells, which have been historically identified as an extension of the nucleus basalis (NB), as well as ChAT− cells, release the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signaling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the BG to modulate frontal cortices. PMID:25739505

  4. Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

    PubMed Central

    Bruns, Tim M; Gaunt, Robert A; Weber, Douglas J

    2011-01-01

    The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2), had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses. PMID:21878706

  5. Microstimulation of afferents in the sacral dorsal root ganglia can evoke reflex bladder activity

    PubMed Central

    Bruns, Tim M; Weber, Douglas J; Gaunt, Robert A

    2013-01-01

    Aims Pudendal afferent fibers can be excited using electrical stimulation to evoke reflex bladder activity. While this approach shows promise for restoring bladder function, stimulation of desired pathways and integration of afferent signals for sensory feedback remains challenging. At sacral dorsal root ganglia (DRG), the convergence of pelvic and pudendal afferent fibers provides a unique location for access to lower urinary tract neurons. Our goal in this study was to demonstrate the potential of microstimulation in sacral DRG for evoking reflex bladder responses. Methods Penetrating microelectrode arrays were inserted in the left S1 and S2 DRG of six anesthetized adult male cats. While the bladder volume was held at a level below the leak volume, single and multiple channel stimulation was performed using various stimulation patterns. Results Reflex bladder excitation was observed in five cats, for stimulation in either S1 or S2 DRG at 1 Hz and 30–33 Hz with a pulse amplitude of 10–50 µA. Bladder relaxation was observed during a few trials. Adjacent electrodes frequently elicited very different responses. Conclusions These results demonstrate the potential of low-current microstimulation to recruit reflexive bladder responses. An approach such as this could be integrated with DRG recordings of bladder afferents to provide a closed-loop bladder neuroprosthesis. PMID:24464833

  6. Increased vitamin D receptor expression in dorsal root ganglia neurons of diabetic rats.

    PubMed

    Filipović, Natalija; Ferhatović, Lejla; Marelja, Ivana; Puljak, Livia; Grković, Ivica

    2013-08-01

    The effects of vitamin D on the nervous system have been studied extensively. In spite of accumulating data about the substantial changes in the vitamin D receptor (VDR) signaling system, during different types of neuroinflammatory diseases, its role in diabetic neuropathy has not been investigated in detail. To assess the role of VDR signaling in diabetic neuropathy, we examined expression of VDRs in dorsal root ganglia (DRG) neurons in a rat model of streptozotocin-induced diabetes mellitus type 1. Diabetes mellitus (DM) type 1 was induced with streptozotocin in male Sprague-Dawley rats. After two months, expression of VDRs was analyzed immunohistochemically in the cytoplasm of L4 and L5 DRG neurons of diabetic rats. Semi-quantitative analysis for the determination of staining in nuclei and plasma-membranes of DRG neurons was performed. A significant increase in VDR expression was observed in DRG neurons of diabetic rats. Expression of VDRs was increased in the cytoplasm, nuclei and in cell membranes of neurons. An increase in VDR expression occurred in all neurons, but the greatest increase of fluorescence intensity in cytoplasm was observed in neurons of small diameter. Results of the present study indicate that the VDR signaling system could be a potential therapeutic target for diabetic neuropathy. PMID:23684983

  7. Antagonistic but Not Symmetric Regulation of Primary Motor Cortex by Basal Ganglia Direct and Indirect Pathways.

    PubMed

    Oldenburg, Ian A; Sabatini, Bernardo L

    2015-06-01

    Motor cortex, basal ganglia (BG), and thalamus are arranged in a recurrent loop whose activity guides motor actions. In the dominant model of the function of the BG and their role in Parkinson's disease, direct (dSPNs) and indirect (iSPNs) striatal projection neurons are proposed to oppositely modulate cortical activity via BG outputs to thalamus. Here, we test this model by determining how striatal activity modulates primary motor cortex in awake head-restrained mice. We find that, within 200 ms, dSPN and iSPN activation exert robust and opposite effects on the majority of cortical neurons. However, these effects are heterogeneous, with certain cortical neurons biphasically modulated by iSPN stimulation. Moreover, these striatal effects are diminished when the animal performs a motor action. Thus, the effects of dSPN and iSPN activity on cortex are at times antagonistic, consistent with classic models, whereas in other contexts these effects can be occluded or coactive. PMID:26050037

  8. Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

    PubMed Central

    Fiore, Vincenzo G.; Rigoli, Francesco; Stenner, Max-Philipp; Zaehle, Tino; Hirth, Frank; Heinze, Hans-Jochen; Dolan, Raymond J.

    2016-01-01

    Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model. PMID:27004463

  9. Exploring neurocircuitries of the basal ganglia by intracerebral administration of selective neurotoxins.

    PubMed

    Herrera-Marschitz, Mario; Bustamante, Diego; Morales, Paola; Goiny, Michel

    2007-04-01

    The detailed anatomy of the monoamine pathways of the rat, first described by the students of Nils Ake Hillarp in Sweden, provided the basis for a neurocircuitry targeted pharmacology, leading to important therapeutic breakthroughs. Progress was achieved by the introduction of accurate lesion techniques based on selective neurotoxins. Systematic intracerebral injections of 6-hydroxydopamine let Urban Ungerstedt at the Karolinska Institutet, Stockholm, Sweden, to propose the first stereotaxic mapping of the monoamine pathways in the rat brain; and the 'Rotational Behaviour', as a classical model for screening drugs useful for alleviating Parkinson's disease and other neuropathologies. The direction of the rotational behaviour induced by drugs administrated to unilaterally 6-hydroxydopamine-lesioned rats reveals their mechanism of action at dopamine synapses, as demonstrated when rotational behaviour was combined with microdialysis. The model was useful for proposing a role for dopamine receptors in the gating of the flow of information integrated and/or modulated by the basal ganglia, through different efferent pathways; notably the striatopallidal system, via D(2) receptors, and the striatonigral system, via D(1) receptors. The role of other dopamine receptor subtypes on rotational behaviour has not yet been clarified. PMID:17449458

  10. CPEB3 Deficiency Elevates TRPV1 Expression in Dorsal Root Ganglia Neurons to Potentiate Thermosensation.

    PubMed

    Fong, Sitt Wai; Lin, Hsiu-Chen; Wu, Meng-Fang; Chen, Chih-Cheng; Huang, Yi-Shuian

    2016-01-01

    Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that downregulates translation of multiple plasticity-related proteins (PRPs) at the glutamatergic synapses. Activity-induced synthesis of PRPs maintains long-lasting synaptic changes that are critical for memory consolidation and chronic pain manifestation. CPEB3-knockout (KO) mice show aberrant hippocampus-related plasticity and memory, so we investigated whether CPEB3 might have a role in nociception-associated plasticity. CPEB3 is widely expressed in the brain and peripheral afferent sensory neurons. CPEB3-KO mice with normal mechanosensation showed hypersensitivity to noxious heat. In the complete Freund's adjuvant (CFA)-induced inflammatory pain model, CPEB3-KO animals showed normal thermal hyperalgesia and transiently enhanced mechanical hyperalgesia. Translation of transient receptor potential vanilloid 1 (TRPV1) RNA was suppressed by CPEB3 in dorsal root ganglia (DRG), whereas CFA-induced inflammation reversed this inhibition. Moreover, CPEB3/TRPV1 double-KO mice behaved like TRPV1-KO mice, with severely impaired thermosensation and thermal hyperalgesia. An enhanced thermal response was recapitulated in non-inflamed but not inflamed conditional-KO mice, with cpeb3 gene ablated mostly but not completely, in small-diameter nociceptive DRG neurons. CPEB3-regulated translation of TRPV1 RNA may play a role in fine-tuning thermal sensitivity of nociceptors. PMID:26915043

  11. Emotional Speech Perception Unfolding in Time: The Role of the Basal Ganglia

    PubMed Central

    Paulmann, Silke; Ott, Derek V. M.; Kotz, Sonja A.

    2011-01-01

    The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages. PMID:21437277

  12. Functional lateralization in cingulate cortex predicts motor recovery after basal ganglia stroke.

    PubMed

    Li, Yao; Chen, Zengai; Su, Xin; Zhang, Xiaoliu; Wang, Ping; Zhu, Yajing; Xu, Qun; Xu, Jianrong; Tong, Shanbao

    2016-02-01

    The basal ganglia (BG) is involved in higher order motor control such as movement planning and execution of complex motor synergies. Neuroimaging study on stroke patients specifically with BG lesions would help to clarify the consequence of BG damage on motor control. In this paper, we performed a longitudinal study in the stroke patients with lesions in BG regions across three motor recovery stages, i.e., less than 2week (Session 1), 1-3m (Session 2) and more than 3m (Session 3). The patients showed an activation shift from bilateral hemispheres during early sessions (<3m) to the ipsilesional cortex in late session (>3m), suggesting a compensation effect from the contralesional hemisphere during motor recovery. We found that the lateralization of cerebellum(CB) for affected hand task correlated with patients' concurrent Fugl-Meyer index (FMI) in Session 2. Moreover, the cingulate cortex lateralization index in Session 2 was shown to significantly correlate with subsequent FMI change between Session 3 and Session 2, which serves as a prognostic marker for motor recovery. Our findings consolidated the close interactions between BG and CB during the motor recovery after stroke. The dominance of activation in contralateral cingulate cortex was associated with a better motor recovery, suggesting the important role of ipsilesional attention modulation in the early stage after BG stroke. PMID:26742641

  13. Mu-opioid receptor (MOR) expression in the human spiral ganglia

    PubMed Central

    Nguyen, Kimanh D.; Mowlds, Donald; Lopez, Ivan A.; Hosokawa, Seiji; Ishiyama, Akira; Ishiyama, Gail

    2015-01-01

    Opioid peptides and their receptors have been localized to the inner ear of the rat and guinea pig mammalian models. The expression of mu opioid receptor (MOR) in the human and mouse cochlea is not yet known. We present MOR protein localization by immunohistochemistry and mRNA expression by in situ hybridization in the human and mouse spiral ganglia (SG) and organ of Corti. In the human most of the (SG) neurons were immunoreactive; a subset was non-immunoreactive. In situ hybridization revealed a similar labeling pattern across the neurons of the SG. A similar distribution MOR pattern was demonstrated in the mouse SG. In the mouse organ of Corti MOR was expressed in inner and outer hair cells. Fibers underneath the inner hair cells were also MOR immunoreactive. These results are consistent with a role of MOR in neuro-modulation of the auditory periphery. The present results show that the expression of MORs is well-conserved across multiple mammalian species, indicative of an important role in auditory processing. PMID:25278190

  14. Role of Beta-Arrestin 2 Downstream of Dopamine Receptors in the Basal Ganglia

    PubMed Central

    Del’Guidice, Thomas; Lemasson, Morgane; Beaulieu, Jean-Martin

    2011-01-01

    Multifunctional scaffolding protein beta-arrestins (?Arr) and the G protein-receptor kinases are involved in the desensitization of several G protein-coupled receptors (GPCR). However, arrestins can also contribute to GPCR signaling independently from G proteins. In this review, we focus on the role of ?Arr in the regulation of dopamine receptor functions in the striatum. First, we present in vivo evidence supporting a role for these proteins in the regulation of dopamine receptor desensitization. Second, we provide an overview of the roles of ?Arr2 in the regulation of extracellular-signal-regulated kinases/MAP kinases and Akt/GSK3 signaling pathways downstream of the D1 and D2 dopamine receptors. Thereafter, we examine the possible involvement of ?Arr-mediated signaling in the action of dopaminergic drugs used for the treatment of mental disorders. Finally, we focus on different potential cellular proteins regulated by ?Arr-mediated signaling which could contribute to the regulation of behavioral responses to dopamine. Overall, the identification of a cell signaling function for ?Arr downstream of dopamine receptors underscores the intricate complexity of the intertwined mechanisms regulating and mediating cell signaling in the basal ganglia. Understanding these mechanisms may lead to a better comprehension of the several roles played by these structures in the regulation of mood and to the development of new psychoactive drugs having better therapeutic efficacy. PMID:21922001

  15. Possible removal route of osmiophilic material (lipofuscin) from spinal ganglia of Torpedo marmorata.

    PubMed

    Glees, P; Aloj Totaro, E; Pisanti, F

    1986-01-01

    The spinal ganglia of Torpedo marmorata have been studied in semithin and ultrathin sections with the view to study the formation and possible mode of removal of lipofuscin. This study suggests that osmiophilic bodies among them lipofuscin originate from degenerating mitochondria. These osmiophilic products concentrate at the neuronal cell border with the satellite cells. The satellite cells have long dense membranous processes which interdigitate, forming a compact myelin sheath but also loosely arranged membranes surrounded by vacuolated plasma. The perinuclear cytoplasmic portion of the satellite cell however contains a rich assemblage of cell organelles well provided for an active metabolism. In this active area which invaginates the neuronal cytoplasm, osmiophilic granules but smaller can be seen, similar to those in the neighbouring neuron. Similar granules are found in cells within the connective tissue space and in the capillary wall. Satellite cells appear not only to be ensheathing cells, providing a perineuronal myelin cover but also capable of removing intra-neuronal debris. It appears that these osmiophilic bodies are taken to the capillary wall by detached satellites or 'handed on' to phagocytes having penetrated between the ensheathing satellites. These cells could take the osmiophilic material to capillaries. PMID:2423586

  16. NUCLEOSIDE PHOSPHATASE AND CHOLINESTERASE ACTIVITIES IN DORSAL ROOT GANGLIA AND PERIPHERAL NERVE

    PubMed Central

    Novikoff, Alex B.; Quintana, Nelson; Villaverde, Humberto; Forschirm, Regina

    1966-01-01

    In dorsal root ganglia and peripheral nerve of the rat and other species, nucleoside phosphatase and unspecific cholinesterase reaction products are found in the plasma membranes and spaces between them at two sites: (1) Schwann cell-axon interfaces and mesaxons of unmyelinated fibers, and (2) sheath cell-perikaryon interfaces and interfaces between adjacent sheath cells. Acetylcholinesterase reaction product is found in the perikaryon (within the endoplasmic reticulum) and the axon (axoplasmic surface). Nucleoside phosphatase reaction product is also found in the numerous vacuoles at the surface of perineurium cells, ganglion sheath cells, and cells surrounding some ganglion blood vessels. Nucleoside phosphatase activities in the sections fail to respond, in the manner described for "transport ATPase," to diisopropylphosphofluoridate, sodium and potassium ions, and ouabain. Nucleoside diphosphates are hydrolyzed more slowly than triphosphates in unmyelinated fibers, and are not hydrolyzed at the perikaryon surface. Nucleoside monophosphates are either not hydrolyzed or hydrolyzed very slowly. In contrast to these localizations, which are believed to demonstrate sites of enzyme activity, it is considered likely that diffusion artifacts account for the nucleoside phosphatase reaction product frequently found along the outer surfaces of myelinated fibers and within vacuoles at the Schwann cell surfaces of these fibers. The diffuse reaction product seen in basement membranes of ganglion and nerve may also be artifact. PMID:4225492

  17. Technical Integration of Hippocampus, Basal Ganglia and Physical Models for Spatial Navigation

    PubMed Central

    Fox, Charles; Humphries, Mark; Mitchinson, Ben; Kiss, Tamas; Somogyvari, Zoltan; Prescott, Tony

    2008-01-01

    Computational neuroscience is increasingly moving beyond modeling individual neurons or neural systems to consider the integration of multiple models, often constructed by different research groups. We report on our preliminary technical integration of recent hippocampal formation, basal ganglia and physical environment models, together with visualisation tools, as a case study in the use of Python across the modelling tool-chain. We do not present new modeling results here. The architecture incorporates leaky-integrator and rate-coded neurons, a 3D environment with collision detection and tactile sensors, 3D graphics and 2D plots. We found Python to be a flexible platform, offering a significant reduction in development time, without a corresponding significant increase in execution time. We illustrate this by implementing a part of the model in various alternative languages and coding styles, and comparing their execution times. For very large-scale system integration, communication with other languages and parallel execution may be required, which we demonstrate using the BRAHMS framework's Python bindings. PMID:19333376

  18. Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training.

    PubMed

    Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-01-01

    Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training. PMID:26035693

  19. Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

    2011-10-01

    The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

  20. CPEB3 Deficiency Elevates TRPV1 Expression in Dorsal Root Ganglia Neurons to Potentiate Thermosensation

    PubMed Central

    Chen, Chih-Cheng; Huang, Yi-Shuian

    2016-01-01

    Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that downregulates translation of multiple plasticity-related proteins (PRPs) at the glutamatergic synapses. Activity-induced synthesis of PRPs maintains long-lasting synaptic changes that are critical for memory consolidation and chronic pain manifestation. CPEB3-knockout (KO) mice show aberrant hippocampus-related plasticity and memory, so we investigated whether CPEB3 might have a role in nociception-associated plasticity. CPEB3 is widely expressed in the brain and peripheral afferent sensory neurons. CPEB3-KO mice with normal mechanosensation showed hypersensitivity to noxious heat. In the complete Freund's adjuvant (CFA)-induced inflammatory pain model, CPEB3-KO animals showed normal thermal hyperalgesia and transiently enhanced mechanical hyperalgesia. Translation of transient receptor potential vanilloid 1 (TRPV1) RNA was suppressed by CPEB3 in dorsal root ganglia (DRG), whereas CFA-induced inflammation reversed this inhibition. Moreover, CPEB3/TRPV1 double-KO mice behaved like TRPV1-KO mice, with severely impaired thermosensation and thermal hyperalgesia. An enhanced thermal response was recapitulated in non-inflamed but not inflamed conditional-KO mice, with cpeb3 gene ablated mostly but not completely, in small-diameter nociceptive DRG neurons. CPEB3-regulated translation of TRPV1 RNA may play a role in fine-tuning thermal sensitivity of nociceptors. PMID:26915043

  1. A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia

    PubMed Central

    Nicolas, Gaël; Jacquin, Agnès; Thauvin-Robinet, Christel; Rovelet-Lecrux, Anne; Rouaud, Olivier; Pottier, Cyril; Aubriot-Lorton, Marie-Hélène; Rousseau, Stéphane; Wallon, David; Duvillard, Christian; Béjot, Yannick; Frébourg, Thierry; Giroud, Maurice; Campion, Dominique; Hannequin, Didier

    2014-01-01

    Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case. PMID:24518837

  2. A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.

    PubMed

    Nicolas, Gaël; Jacquin, Agnès; Thauvin-Robinet, Christel; Rovelet-Lecrux, Anne; Rouaud, Olivier; Pottier, Cyril; Aubriot-Lorton, Marie-Hélène; Rousseau, Stéphane; Wallon, David; Duvillard, Christian; Béjot, Yannick; Frébourg, Thierry; Giroud, Maurice; Campion, Dominique; Hannequin, Didier

    2014-10-01

    Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case. PMID:24518837

  3. Culture of dissociated sensory neurons from dorsal root ganglia of postnatal and adult rats.

    PubMed

    Owen, Davina E; Egerton, Julie

    2012-01-01

    The development of new therapeutics for management of pain is likely to become much more mechanism based, and therefore, we need a more thorough understanding of the different pain development pathways. The afferent fibers of sensory neurons, with their cell bodies in the dorsal root ganglia (DRG), are thought to be key in pain mechanisms. DRG neurons can be prepared from embryonic, postnatal, or adult tissue. Embryonic preparations have the advantage of higher cell yields and greater proportion of neurons, but they are dependent on neurotrophins for the first week of culture. In contrast, dissociated postnatal and adult DRG sensory neurons offer the possibility to study mature neurons that may better resemble the in vivo characteristics of these cells. Here, we describe the dissociation of DRG sensory neurons from postnatal and adult rats. DRG are dissected and dissociated using a prolonged trypsin/collagenase treatment, followed by mechanical separation of the neurons. We have routinely prepared them for electrophysiological studies by the methods outlined in this chapter and describe some of the pitfalls that we have encountered, with hints of how to overcome them. PMID:22367811

  4. Multiplicity of control in the basal ganglia: computational roles of striatal subregions.

    PubMed

    Bornstein, Aaron M; Daw, Nathaniel D

    2011-06-01

    The basal ganglia, in particular the striatum, are central to theories of behavioral control, and often identified as a seat of action selection. Reinforcement learning (RL) models--which have driven much recent experimental work on this region--cast striatum as a dynamic controller, integrating sensory and motivational information to construct efficient and enriching behavioral policies. Befitting this informationally central role, the BG sit at the nexus of multiple anatomical 'loops' of synaptic projections, connecting a wide range of cortical and subcortical structures. Numerous pioneering anatomical studies conducted over the past several decades have meticulously catalogued these loops, and labeled them according to the inferred functions of the connected regions. The specific cotermina of the projections are highly localized to several different subregions of the striatum, leading to the suggestion that these subregions perform complementary but distinct functions. However, until recently, the dominant computational framework outlined only a bipartite, dorsal/ventral, division of striatum. We review recent computational and experimental advances that argue for a more finely fractionated delineation. In particular, experimental data provide extensive insight into unique functions subserved by the dorsomedial striatum (DMS). These functions appear to correspond well with theories of a 'model-based' RL subunit, and may also shed light on the suborganization of ventral striatum. Finally, we discuss the limitations of these ideas and how they point the way toward future refinements of neurocomputational theories of striatal function, bringing them into contact with other areas of computational theory and other regions of the brain. PMID:21429734

  5. Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.

    PubMed

    Fiore, Vincenzo G; Rigoli, Francesco; Stenner, Max-Philipp; Zaehle, Tino; Hirth, Frank; Heinze, Hans-Jochen; Dolan, Raymond J

    2016-01-01

    Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson's disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model. PMID:27004463

  6. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection.

    PubMed

    Baston, Chiara; Ursino, Mauro

    2015-01-01

    The basal ganglia (BG) are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go), indirect (NoGo), and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves) during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges), synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication). Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments. PMID:26640481

  7. Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome.

    PubMed

    Wortmann, Saskia B; van Hasselt, Peter M; Barić, Ivo; Burlina, Alberto; Darin, Niklas; Hörster, Friederike; Coker, Mahmut; Ucar, Sema Kalkan; Krumina, Zita; Naess, Karin; Ngu, Lock H; Pronicka, Ewa; Riordan, Gilian; Santer, Rene; Wassmer, Evangeline; Zschocke, Johannes; Schiff, Manuel; de Meirleir, Linda; Alowain, Mohammed A; Smeitink, Jan A M; Morava, Eva; Kozicz, Tamas; Wevers, Ron A; Wolf, Nicole I; Willemsen, Michel A

    2015-04-01

    Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings. PMID:25642805

  8. Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

    PubMed Central

    Garcia, Leah A.; Hlaing, Su M.; Gutierrez, Richard A.; Sanchez, Maria D.; Kovanecz, Istvan; Artaza, Jorge N.; Ferrini, Monica G.

    2014-01-01

    Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i) have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR) by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1) ?, IL-6, IL-10, transforming growth factor ? 1 (TGF?1), and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), TNF receptor superfamily member 5 (CD40) that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration. PMID:25264738

  9. Sildenafil attenuates inflammation and oxidative stress in pelvic ganglia neurons after bilateral cavernosal nerve damage.

    PubMed

    Garcia, Leah A; Hlaing, Su M; Gutierrez, Richard A; Sanchez, Maria D; Kovanecz, Istvan; Artaza, Jorge N; Ferrini, Monica G

    2014-01-01

    Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i) have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR) by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1) ?, IL-6, IL-10, transforming growth factor ? 1 (TGF?1), and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), TNF receptor superfamily member 5 (CD40) that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration. PMID:25264738

  10. A model of the basal ganglia in voluntary movement and postural reactions.

    PubMed

    Hemami, Hooshang; Moussavi, Zahra

    2014-01-01

    A basal ganglia central pattern generator (CPG) is developed and its role in voluntary movements on the ground and postural reactions on a disturbed platform are studied and analysed by simulation. Biped dynamics and platform kinematics are utilised. The effects of agonist-antagonist muscular co-activation and joint stiffness are formulated. The implementation of the necessary counter-manoeuvres for maintaining balance and postural stability is studied. A control strategy, applicable to large systems, is formulated. The biped manoeuvres and transitions terminate in pre-specified intervals of time. Gravity is included and compensated for. Certain voluntary and postural adjustment strategies are the same but are initiated differently. Further experimental/computational research may identify the central nervous system and sensory paths that lead to the CPG. All actuator forces linearly evolve in time from their original values to their terminal values. There are no central continuous feedback loops present. Monitoring and sensing, however, are ongoing. The counter-manoeuvres are based on learned human-like voluntary movements that are triggered by the disturbance. The required central inputs to the musculoskeletal system are designed in the CPG. A functional structure for the CPG is proposed. The effect of certain disorders and malfunctions of the CPG are studied by simulation. PMID:23282072

  11. RIA/chromatographic evidence for novel opioid peptide(s) in Squilla mantis ganglia.

    PubMed

    Palmisano, A; Marino, G; Di Marzo, V; Morris, H R; Howlett, T A; Tomlin, S

    1986-04-01

    Proteins extracted from suboesophageal ganglia of Squilla mantis, an arthropod shown to be sensitive in vivo to opiates and to contain native opioid like peptide(s), were fractionated by gel filtration into three pools according to their molecular weight: A (Mr greater than 65,000), B (10,000 less than Mr less than 65,000) and C (Mr less than 10,000). None of these pools showed any immunoreactivity when radioimmunoassayed using antisera raised against Met-enkephalin either before or after sequential trypsin/carboxypeptidase B proteolysis. Further purification of pool C by HPLC followed by RIA using antibodies directed to Met-O-enkephalin,Leu-enkephalin,Dynorphin 1-13 and human beta-endorphin, showed only a trace amount of Met-enkephalin cross-reactivity (about 10 fmoles/mg of protein extract). No detectable amount of Leu- or Met-enkephalin was found after HPLC fractionation of proteolyzed pool B. Radioreceptor assay of HPLC fractions derived from trypsin/carboxypeptidase B treated pools B and C showed major areas of activity common to both pools, but nevertheless with differing retention times compared to the standard opioid peptides used. PMID:2872612

  12. A role for the basal ganglia in nicotinic modulation of the blink reflex.

    PubMed

    Evinger, C; Basso, M A; Manning, K A; Sibony, P A; Pellegrini, J J; Horn, A K

    1993-01-01

    In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D2) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D2 receptor agonist, mimicked the effects of nicotine on the blink reflex. PMID:8454014

  13. Cost-efficient FPGA implementation of basal ganglia and their Parkinsonian analysis.

    PubMed

    Yang, Shuangming; Wang, Jiang; Li, Shunan; Deng, Bin; Wei, Xile; Yu, Haitao; Li, Huiyan

    2015-11-01

    The basal ganglia (BG) comprise multiple subcortical nuclei, which are responsible for cognition and other functions. Developing a brain-machine interface (BMI) demands a suitable solution for the real-time implementation of a portable BG. In this study, we used a digital hardware implementation of a BG network containing 256 modified Izhikevich neurons and 2048 synapses to reliably reproduce the biological characteristics of BG on a single field programmable gate array (FPGA) core. We also highlighted the role of Parkinsonian analysis by considering neural dynamics in the design of the hardware-based architecture. Thus, we developed a multi-precision architecture based on a precise analysis using the FPGA-based platform with fixed-point arithmetic. The proposed embedding BG network can be applied to intelligent agents and neurorobotics, as well as in BMI projects with clinical applications. Although we only characterized the BG network with Izhikevich models, the proposed approach can also be extended to more complex neuron models and other types of functional networks. PMID:26318085

  14. Ganglionectomy without Repairing the Bursal Defect: Long-term Results in a Series of 124 Wrist Ganglia

    PubMed Central

    Dermon, Antonios; Fiska, Aliki; Alpantaki, Kalliopi; Kazakos, Konstantinos

    2011-01-01

    Background Some surgeons consider the abscission of a part of the articular bursa around the point of the input of ganglion's nape (average 1-2 cm diameter) to be very important with excellent results. However, a literature search revealed disagreement as to whether it is essential to repair a bursa defect. This study examined the effectiveness of this method without repairing the articular defect. An attempt was made to identify the anatomical origin of wrist ganglia during the surgical procedure. Methods This study evaluated 124 wrist ganglia that had been treated surgically during 2004-2009 using this technique and without repairing the bursa defect (1-2 cm in diameter). The variables studied were age, gender, time from the occurrence till abscission of the ganglia, former surgical interventions, preoperative and postoperative pain, insertion of the ganglion's nape and complications. Sixty-six patients with a mean follow-up of 42 months and minimum 12 months were examined. Results At the time of the follow-up, 80.3% had no pain whereas 92.2% showed a remarkable improvement. Seven cases of recurrence (10.6%) were found 2 to 85 months after surgery, of which most appeared during the first year (71.4%). It is important to mention that the majority of the dorsal ganglia (42.8%) originated from the capitate-lunate joint. None of the patients presented with scapholunate or other instability. Conclusions This surgical method is a simple and safe with excellent long-term results and a lower recurrence rate compared to other surgical approaches. Overall, repair of the articular bursa is unnecessary. PMID:21629477

  15. A spiking neuron model of the cortico-basal ganglia circuits for goal-directed and habitual action learning.

    PubMed

    Chersi, Fabian; Mirolli, Marco; Pezzulo, Giovanni; Baldassarre, Gianluca

    2013-05-01

    Dual-system theories postulate that actions are supported either by a goal-directed or by a habit-driven response system. Neuroimaging and anatomo-functional studies have provided evidence that the prefrontal cortex plays a fundamental role in the first type of action control, while internal brain areas such as the basal ganglia are more active during habitual and overtrained responses. Additionally, it has been shown that areas of the cortex and the basal ganglia are connected through multiple parallel "channels", which are thought to function as an action selection mechanism resolving competitions between alternative options available in a given context. In this paper we propose a multi-layer network of spiking neurons that implements in detail the thalamo-cortical circuits that are believed to be involved in action learning and execution. A key feature of this model is that neurons are organized in small pools in the motor cortex and form independent loops with specific pools of the basal ganglia where inhibitory circuits implement a multistep selection mechanism. The described model has been validated utilizing it to control the actions of a virtual monkey that has to learn to turn on briefly flashing lights by pressing corresponding buttons on a board. When the animal is able to fluently execute the task the button-light associations are remapped so that it has to suppress its habitual behavior in order to execute goal-directed actions. The model nicely shows how sensory-motor associations for action sequences are formed at the cortico-basal ganglia level and how goal-directed decisions may override automatic motor responses. PMID:23266482

  16. Presynaptic Inhibition in the Striatum of the Basal Ganglia Improves Pattern Classification and Thus Promotes Superior Goal Selection

    PubMed Central

    Schwab, David J.; Houk, James C.

    2015-01-01

    This review article takes a multidisciplinary approach to understand how presynaptic inhibition in the striatum of the basal ganglia (BG) contributes to pattern classification and the selection of goals that control behavior. It is a difficult problem both because it is multidimensional and because it is has complex system dynamics. We focus on the striatum because, as the main site for input to the BG, it gets to decide what goals are important to consider. PMID:26696840

  17. Presynaptic Inhibition in the Striatum of the Basal Ganglia Improves Pattern Classification and Thus Promotes Superior Goal Selection.