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Ablation of Ca2+ channel beta 3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory
No full textThe beta subunits of voltage-dependent Ca2+ channels (VDCCs) have marked effects on the properties of the pore-forming alpha(1) subunits of VDCCs, including surface expression of channel complexes and modification of voltage-dependent kinetics. Among the four different beta subunits, the beta 3 subunit (Ca-v beta 3) is abundantly expressed in the hippocampus. However, the role of Ca-v beta 3 in hippocampal physiology and function in vivo has never been examined. Here, we investigated Ca-v beta 3-deficient mice for hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses. Interestingly, the mutant mice exhibited enhanced performance in several hippocampus-dependent learning and memory tasks. However, electrophysiological studies revealed no alteration in the Ca2+ current density, the frequency and amplitude of miniature excitatory postsynaptic currents, and the basal synaptic transmission in the mutant hippocampus. On the other hand, however, N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents and NMDAR-dependent long term potentiation were significantly increased in the mutant. Protein blot analysis showed a slight increase in the level of NMDAR-2B in the mutant hippocampus. Our results suggest a possibility that, unrelated to VDCCs regulation, Ca-v beta 3 negatively regulates the NMDAR activity in the hippocampus and thus activity-dependent synaptic plasticity and cognitive behaviors in the mouse.This work was supported by the National Honor Scientist Program of Korea, grants from Korea Institute of Science and Technology, the National Creative Research Initiatives of the Ministry of Science and Technology of Korea, and Virginia Commonwealth University Medical Center Grant NEI EY12716. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact
Tracing the evolution of multi-scale functional networks in a mouse model of depression using persistent brain network homology
No full textMany brain diseases or disorders, such as depression, are known to be associated with abnormal functional connectivity in neural networks in the brain. Some bivariate measures of electroencephalography (EEG) for coupling analysis have been used widely in attempts to explain abnormalities related with depression. However, brain network evolution based on persistent functional connections in EEG signals could not be easily unveiled. For a geometrical exploration of brain network evolution, here, we used persistent brain network homology analysis with EEG signals from a corticosterone (CORT)-induced mouse model of depression. EEG signals were obtained from eight cortical regions (frontal, somatosensory, parietal, and visual cortices in each hemisphere). The persistent homology revealed a significantly different functional connectivity between the control and CORT model, but no differences in common coupling measures, such as cross correlation and coherence, were apparent. The CORT model showed a more localized connectivity and decreased global connectivity than the control. In particular, the somatosensory and parietal cortices were loosely connected in the CORT model. Additionally, the CORT model displayed altered connections among the cortical regions, especially between the frontal and somatosensory cortices, versus the control. This study demonstrates that persistent homology is useful for brain network analysis, and our results indicate that the CORT-induced depression mouse model shows more localized and decreased global connectivity with altered connections, which may facilitate characterization of the abnormal brain network underlying depression
Enhanced Learning and Memory in Mice Lacking Na+/Ca2+ Exchanger 2
No full textAbstractThe plasma membrane Na+/Ca2+ exchanger (NCX) plays a role in regulation of intracellular Ca2+ concentration via the forward mode (Ca2+ efflux) or the reverse mode (Ca2+ influx). To define the physiological function of the exchanger in vivo, we generated mice deficient for NCX2, the major isoform in the brain. Mutant hippocampal neurons exhibited a significantly delayed clearance of elevated Ca2+ following depolarization. The frequency threshold for LTP and LTD in the hippocampal CA1 region was shifted to a lowered frequency in the mutant mice, thereby favoring LTP. Behaviorally, the mutant mice exhibited enhanced performance in several hippocampus-dependent learning and memory tasks. These results demonstrate that NCX2 can be a temporal regulator of Ca2+ homeostasis and as such is essential for the control of synaptic plasticity and cognition
Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC
No full textFear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Ca(v)1.2 Ca2+ channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Ca(v)1.2 channels of the ACC in observational social fear
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats.
No full textTransplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and beta galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-beta gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus
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