1,726,162 research outputs found
Replication of Postural Hand Synergies for Tool Use by Santello et al., J. Neurosci., 1998
Replication of the experiment performed in Postural Hand Synergies for Tool Use by Santello et al. (J. Neurosci., 1998) using a Microsoft Hololens in place of Virtual Technologies Cyberglove to record hand joint angles; key test: whether first two principal components of joint poses explain more than 80% of the variance in static hand posture during tool use
Replication of Postural Hand Synergies for Tool Use by Santello et al., J. Neurosci., 1998
Replication of the experiment performed in Postural Hand Synergies for Tool Use by Santello et al. (J. Neurosci., 1998) using a Microsoft Hololens in place of Virtual Technologies Cyberglove to record hand joint angles; key test: whether first two principal components of joint poses explain more than 80% of the variance in static hand posture during tool use
Imaging the spread of reversible brain inactivations using fluorescent muscimol
Author manuscript. Published in final edited form as:
J Neurosci Methods. 2008 June 15; 171(1): 30–38
J Neurosci
Growth-associated protein of 43 kDa (GAP43) is a key cytoskeleton-associated component of the presynaptic terminal that facilitates neuroplasticity. Downregulation of GAP43 expression has been associated to various psychiatric conditions in humans and evokes hippocampus-dependent memory impairments in mice. Despite the extensive studies conducted on hippocampal GAP43 in past decades, however, very little is known about its roles in modulating the excitatory versus inhibitory balance in other brain regions. We recently generated conditional knock-out mice in which the Gap43 gene was selectively inactivated in either telencephalic glutamatergic neurons ( Gap43 fl/fl ; Nex1 Cre mice, hereafter Glu-GAP43 −/− mice) or forebrain GABAergic neurons ( Gap43 fl/fl ; Dlx5/6 Cre mice, hereafter GABA-GAP43 −/− mice). Here, we show that Glu-GAP43 −/− but not GABA-GAP43 −/− mice of either sex show a striking hyperactive phenotype when exposed to a novel environment. This behavioral alteration of Glu-GAP43 −/− mice was linked to a selective activation of dorsal-striatum neurons, as well as to an enhanced corticostriatal glutamatergic transmission and an abrogation of corticostriatal endocannabinoid-mediated long-term depression. In line with these observations, GAP43 was abundantly expressed in corticostriatal glutamatergic terminals of wild-type mice. The novelty-induced hyperactive phenotype of Glu-GAP43 −/− mice was abrogated by chemogenetically inhibiting corticostriatal afferences with a G i -coupled “designer receptor exclusively activated by designer drugs” (DREADDs), thus further supporting that novelty-induced activity is controlled by GAP43 at corticostriatal excitatory projections. Taken together, these findings show an unprecedented regulatory role of GAP43 in the corticostriatal circuitry and provide a new mouse model with a delimited neuronal-circuit alteration for studying novelty-induced hyperactivity, a phenotypic shortfall that occurs in diverse psychiatric diseases
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Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy
Neurofibrillary tangles (NFTs) are associated with neuronal loss and correlate with cognitive impairment in Alzheimer disease, but how NFTs relate to neuronal death is not clear. We studied cell death in Tg4510 mice that reversibly express P301L mutant human tau and accumulate NFTs using in vivo multiphoton imaging of neurofibrillary pathology, propidium iodide (PI) incorporation into cells, caspase activation, and DNA labeling. We first observed that in live mice, a minority of neurons were labeled with the caspase probe or with PI fluorescence. These markers of cell stress were localized in the same cells and appeared specifically within NFT-bearing neurons. Contrary to expectations, the PI-stained neurons did not die during a day of observation; the presence of Hoechst-positive nuclei in them on the subsequent day indicated that the NFT-associated membrane disruption, as suggested by PI staining, and caspase activation do not lead to immediate death of neurons in this tauopathy model. This unique combination of in vivo multiphoton imaging with markers of cell death and pathological alteration is a powerful tool for investigating neuronal damage associated with neurofibrillary pathology
Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation
The study of protein function in neurons has been hindered by the lack of highly efficient, nontoxic methods of inducing RNA interference in such cells. Here we show that application of synthetic small interfering RNA( siRNA) linked to the vector peptide Penetratin1 results in rapid, highly efficient uptake of siRNA by entire populations of cultured primary mammalian hippocampal and sympathetic neurons. This treatment leads to specific knock-down of targeted proteins within hours without the toxicity associated with transfection. In contrast to current methods, our technique permits study of protein function across entire populations with minimal disturbance of complex cellular networks. Using this technique, we found that protein knock-down ( evident after 6 hr) precedes any decrease in targeted message ( evident after 24 hr), suggesting an early, translational repression by perfectly targeted siRNAs.PT: J; CR: BARTEL DP, 2004, CELL, V116, P281 BERTRAND E, 2001, MOL CELL NEUROSCI, V18, P503 DEROSSI D, 1994, J BIOL CHEM, V269, P10444 DOENCH JG, 2003, GENE DEV, V17, P438 DOSTIE JE, 2003, RNA, V9, P180 ELBASHIR SM, 2001, EMBO J, V20, P6877 FINK CC, 2003, NEURON, V39, P283 FIRE A, 1998, NATURE, V391, P806 GAUDILLIERE B, 2002, J BIOL CHEM, V277, P46442 HANNON GJ, 2002, NATURE, V418, P244 HUTVAGNER G, 2002, SCIENCE, V297, P2056 JOHNSTON RJ, 2003, NATURE, V426, P845 JOLIOT A, 2004, NAT CELL BIOL, V6, P189 KHVOROVA A, 2003, CELL, V115, P209 KIM J, 2004, P NATL ACAD SCI USA, V101, P360 KRICHEVSKY AM, 2002, P NATL ACAD SCI USA, V99, P11926 KRICHEVSKY AM, 2003, RNA, V9, P1274 LAI EC, 2003, CURR BIOL, V13, R925 LLAVE C, 2002, SCIENCE, V297, P2053 MURATOVSKA A, 2004, FEBS LETT, V558, P63 OMI K, 2004, FEBS LETT, V558, P89 RABACCHI SA, 2004, NEUROBIOL AGING, V25, P1057 REYNOLDS A, 2004, NAT BIOTECHNOL, V22, P326 SAXENA S, 2003, J BIOL CHEM, V278, P44312 SCHERER LJ, 2003, NAT BIOTECHNOL, V21, P1457 SCHWARZ DS, 2003, CELL, V115, P199 THEODORE L, 1995, J NEUROSCI, V15, P7158 TOROCSIK B, 2002, J NEUROSCI, V22, P8971 TROY CM, 1994, P NATL ACAD SCI USA, V91, P6384 TROY CM, 1996, J NEUROSCI, V16, P253 TROY CM, 1996, P NATL ACAD SCI USA, V93, P5635 TROY CM, 2001, J NEUROSCI, V21, P5007 TROY CM, 2002, J BIOL CHEM, V277, P34295 VICKERS TA, 2003, J BIOL CHEM, V278, P7108 ZENG Y, 2003, P NATL ACAD SCI USA, V100, P9779; NR: 35; TC: 22; J9: J NEUROSCI; PG: 7; GA: 869ZASource type: Electronic(1
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Differences in Photoreceptor Processing Speed for Chromatic and Achromatic Vision in the Bumblebee, Bombus terrestris
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