1,720,991 research outputs found
Place Cell Activity in Disc1-L100P Mutant Mice
No full textDISC1 is an established susceptibility gene for schizophrenia. To gain insight on the neural mechanisms responsible for hippocampal deficits in schizophrenia, we sought to characterize place cell activity and theta rhythm in our Disc1-L100P mouse strain that we have previously shown to express deficits in spatial working memory. Our findings suggest that the rate code of place cells is intact. We found that Disc1-L100P mice have deficits in theta rhythm, increased neural noise, and lower levels of PV+ interneurons in the hippocampus. Our findings are supportive of impaired temporal coding in Disc1-L100P place cells. We found that Disc1-L100P place cell waveforms were broader than those of wild-type mice and putative interneuron waveforms were narrower. These findings suggest that ion-channel function and expression in the hippocampus is altered in Disc1-L100P mice. In schizophrenic subjects deficits in working memory are associated with aberrant oscillatory activity, increased noise, and lower PV+ interneuron expression.MAS
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Place Cell Activity in Disc1-L100P Mutant Mice
No full textDISC1 is an established susceptibility gene for schizophrenia. To gain insight on the neural mechanisms responsible for hippocampal deficits in schizophrenia, we sought to characterize place cell activity and theta rhythm in our Disc1-L100P mouse strain that we have previously shown to express deficits in spatial working memory. Our findings suggest that the rate code of place cells is intact. We found that Disc1-L100P mice have deficits in theta rhythm, increased neural noise, and lower levels of PV+ interneurons in the hippocampus. Our findings are supportive of impaired temporal coding in Disc1-L100P place cells. We found that Disc1-L100P place cell waveforms were broader than those of wild-type mice and putative interneuron waveforms were narrower. These findings suggest that ion-channel function and expression in the hippocampus is altered in Disc1-L100P mice. In schizophrenic subjects deficits in working memory are associated with aberrant oscillatory activity, increased noise, and lower PV+ interneuron expression.MAS
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The Role of SRC Tyrosine Kinase in Synaptic Plasticity and Neurologica Disorder
Get PDFThe non-receptor protein tyrosine kinase Src is expressed throughout the central nervous system and is involved in diverse biological functions like cell growth, differentiation, and postsynaptic signalling. Despite the well-documented functions of Src in hippocampal synaptic plasticity, roles in social behaviours, motor function, cognition, and synaptic signalling in other brain regions remain largely untested. This work investigates the neurocellular and behavioural effects of in-vivo inhibition and disinhibition of the Src tyrosine kinase pathway in mice. To this end, we employed a cell permeant Src inhibitory peptide, mutant mice harbouring a loss-of-function point mutation in Src, and a mutant mouse with deficits in the inhibitory C-terminal Src kinase (Csk). Alterations in Src signalling were associated with profound changes in NMDA receptor signalling, synaptic plasticity, motor function, cued fear conditioning, and a variety of social behaviours, underscoring the ubiquity and importance of Src signalling in the mammalian central nervous system.
Blocking the interaction of the Src tyrosine kinase with the NMDAR complex impaired auditory conditioned fear memory and social recognition. Inhibition of Src-NMDAR interactions also attenuated NR2B phosphorylation and decreased NR2B surface expression in the amygdala. Furthermore, at the lateral to basolateral nucleus pathway (LA-BLA), inhibition of Src impaired long-term potentiation. Mice harbouring a Src point mutation (Src(thl/thl) mice) exhibited behavioural abnormalities and growth retardation. We also observed differences in behaviour phenotypes analogous to mouse models of Williams-Beuren syndrome (WBS) and humans with WBS . WBS is neurodevelopmental disorder characterized by distinctive facial features, hypersociability, mild to moderate mental retardation, and a unique cognitive disability (Meyer-Lindenberg et al., 2006). Sociability and social vocalization were increased in three different social affiliation tasks in Src(thl/thl) mice. Mutant mice exhibited hyperactivity in the open field and spent significantly less time in the centre of the open field. Also, motor function was impaired in three different motor performance tasks. The Src(thl/thl) mice showed an enhanced startle response to loud stimuli, impaired cued fear conditioning, and deficient visiospatial memory in the Morris water maze. Furthermore, Src(thl/thl) mice were not able to learn a visual object recognition task. These results underscore the importance of Src in an array of behavioural, motor, and cognitive functions in mice.
The C-terminal Src kinase (Csk) acts to suppress Src activity, so Csk(+/-) mice were employed to examine the behavioural impact of enhanced Src signalling. Decreased Csk expression led to enhanced long-term and short-term social olfactory recognition and social transmission of food preference. We also found elevated NR2B phosphorylation in the olfactory bulb and amygdala, two brain regions critical for the behavioural expression of anxiety and social recognition in mice.
Deficiencies in the Src tyrosine kinase pathway were associated with impaired synaptic plasticity in the amygdala and behaviour disturbances that are relevant to WBS. Conversely, up-regulation of the Src tyrosine kinase pathway by reducing Csk expression increased social olfactory cognition. A more detailed understanding of the Src pathway could facilitate the development of new treatments for diseases characterized by aberrant social behaviours.Ph
The Role of SRC Tyrosine Kinase in Synaptic Plasticity and Neurologica Disorder
No full textThe non-receptor protein tyrosine kinase Src is expressed throughout the central nervous system and is involved in diverse biological functions like cell growth, differentiation, and postsynaptic signalling. Despite the well-documented functions of Src in hippocampal synaptic plasticity, roles in social behaviours, motor function, cognition, and synaptic signalling in other brain regions remain largely untested. This work investigates the neurocellular and behavioural effects of in-vivo inhibition and disinhibition of the Src tyrosine kinase pathway in mice. To this end, we employed a cell permeant Src inhibitory peptide, mutant mice harbouring a loss-of-function point mutation in Src, and a mutant mouse with deficits in the inhibitory C-terminal Src kinase (Csk). Alterations in Src signalling were associated with profound changes in NMDA receptor signalling, synaptic plasticity, motor function, cued fear conditioning, and a variety of social behaviours, underscoring the ubiquity and importance of Src signalling in the mammalian central nervous system.
Blocking the interaction of the Src tyrosine kinase with the NMDAR complex impaired auditory conditioned fear memory and social recognition. Inhibition of Src-NMDAR interactions also attenuated NR2B phosphorylation and decreased NR2B surface expression in the amygdala. Furthermore, at the lateral to basolateral nucleus pathway (LA-BLA), inhibition of Src impaired long-term potentiation. Mice harbouring a Src point mutation (Src(thl/thl) mice) exhibited behavioural abnormalities and growth retardation. We also observed differences in behaviour phenotypes analogous to mouse models of Williams-Beuren syndrome (WBS) and humans with WBS . WBS is neurodevelopmental disorder characterized by distinctive facial features, hypersociability, mild to moderate mental retardation, and a unique cognitive disability (Meyer-Lindenberg et al., 2006). Sociability and social vocalization were increased in three different social affiliation tasks in Src(thl/thl) mice. Mutant mice exhibited hyperactivity in the open field and spent significantly less time in the centre of the open field. Also, motor function was impaired in three different motor performance tasks. The Src(thl/thl) mice showed an enhanced startle response to loud stimuli, impaired cued fear conditioning, and deficient visiospatial memory in the Morris water maze. Furthermore, Src(thl/thl) mice were not able to learn a visual object recognition task. These results underscore the importance of Src in an array of behavioural, motor, and cognitive functions in mice.
The C-terminal Src kinase (Csk) acts to suppress Src activity, so Csk(+/-) mice were employed to examine the behavioural impact of enhanced Src signalling. Decreased Csk expression led to enhanced long-term and short-term social olfactory recognition and social transmission of food preference. We also found elevated NR2B phosphorylation in the olfactory bulb and amygdala, two brain regions critical for the behavioural expression of anxiety and social recognition in mice.
Deficiencies in the Src tyrosine kinase pathway were associated with impaired synaptic plasticity in the amygdala and behaviour disturbances that are relevant to WBS. Conversely, up-regulation of the Src tyrosine kinase pathway by reducing Csk expression increased social olfactory cognition. A more detailed understanding of the Src pathway could facilitate the development of new treatments for diseases characterized by aberrant social behaviours.Ph
The Role of the Glutamatergic System in Psychiatric Behavioral Endophenotypes in Mice: Implications for Schizophrenia
No full textReduced activity of the N-methyl-D-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. The NMDAR contains a glycine site on the NR1 subunit that may be a promising therapeutic target for psychiatric illness. Recently, D-serine has been discovered to be a high-affinity endogenous activator of the NMDAR glycine site. Levels of D-serine in the brain are controlled by its synthesis enzyme serine racemase (Srr) and its catabolic enzyme D-amino acid oxidase (DAO). This work investigates the NMDAR glycine site, D-serine, and D-serine-regulatory enzymes Srr and DAO in the pathophysiology and treatment of symptomatology relevant to schizophrenia and other psychiatric disorders. Pharmacological and genetic mouse models were used to alter glycine site function and D-serine availability. Behavioral responses in these models were assessed. Administration of exogenous D-serine and the glycine transporter 1 (GlyT-1) inhibitor ALX-5407 improved performance of C57BL/6J mice in behavioral tests examining prepulse inhibition (PPI) or latent inhibition (LI). These compounds also reversed impairments induced by the NMDAR antagonist MK-801, and produced similar beneficial effects to the classical atypical antipsychotic clozapine. Mice carrying a point mutation that leads to diminished NMDAR glycine site function demonstrated abnormally persistent LI and deficits in social approach and spatial recognition that were reversible by D-serine or clozapine administration. Similarly, mutant mice that lacked Srr function and had a severe reduction in D-serine displayed impairments in sociability, PPI, spatial recognition and memory. Behavioral deficits in mice without Srr were exacerbated by MK-801 and rescued by treatment with D-serine or clozapine. A genetically-induced loss of DAO function in mice resulted in the elevation of brain D-serine levels, and produced improvements in spatial reversal memory and extinction of a learned response in the Morris water maze, consistent with the effects of exogenous D-serine application in wild-type mice. Thus, deficiencies in NMDAR glycine site function and D-serine availability produce behavioral disturbances that are relevant to the negative and cognitive symptoms of schizophrenia. Activation of the NMDAR glycine site by D-serine, GlyT-1 inhibition, or diminished DAO activity may be beneficial for the treatment of schizophrenia and other psychopathologies involving cognitive dysfunction and persistent repetitive behaviors.Ph
The Role of the Glutamatergic System in Psychiatric Behavioral Endophenotypes in Mice: Implications for Schizophrenia
Get PDFReduced activity of the N-methyl-D-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. The NMDAR contains a glycine site on the NR1 subunit that may be a promising therapeutic target for psychiatric illness. Recently, D-serine has been discovered to be a high-affinity endogenous activator of the NMDAR glycine site. Levels of D-serine in the brain are controlled by its synthesis enzyme serine racemase (Srr) and its catabolic enzyme D-amino acid oxidase (DAO). This work investigates the NMDAR glycine site, D-serine, and D-serine-regulatory enzymes Srr and DAO in the pathophysiology and treatment of symptomatology relevant to schizophrenia and other psychiatric disorders. Pharmacological and genetic mouse models were used to alter glycine site function and D-serine availability. Behavioral responses in these models were assessed. Administration of exogenous D-serine and the glycine transporter 1 (GlyT-1) inhibitor ALX-5407 improved performance of C57BL/6J mice in behavioral tests examining prepulse inhibition (PPI) or latent inhibition (LI). These compounds also reversed impairments induced by the NMDAR antagonist MK-801, and produced similar beneficial effects to the classical atypical antipsychotic clozapine. Mice carrying a point mutation that leads to diminished NMDAR glycine site function demonstrated abnormally persistent LI and deficits in social approach and spatial recognition that were reversible by D-serine or clozapine administration. Similarly, mutant mice that lacked Srr function and had a severe reduction in D-serine displayed impairments in sociability, PPI, spatial recognition and memory. Behavioral deficits in mice without Srr were exacerbated by MK-801 and rescued by treatment with D-serine or clozapine. A genetically-induced loss of DAO function in mice resulted in the elevation of brain D-serine levels, and produced improvements in spatial reversal memory and extinction of a learned response in the Morris water maze, consistent with the effects of exogenous D-serine application in wild-type mice. Thus, deficiencies in NMDAR glycine site function and D-serine availability produce behavioral disturbances that are relevant to the negative and cognitive symptoms of schizophrenia. Activation of the NMDAR glycine site by D-serine, GlyT-1 inhibition, or diminished DAO activity may be beneficial for the treatment of schizophrenia and other psychopathologies involving cognitive dysfunction and persistent repetitive behaviors.Ph
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