1,721,029 research outputs found
Replication Data for Questioning More: RT, Outward Facing Propaganda, and the Post-West World Order
No full textThese files constitute the replication information for "Questioning More: RT, Outward Facing Propaganda, and the Post-West World Order," published in Security Studies
Regional Governance in Divided Societies: Evidence from the Republic of Congo and Kenya
No full textReplication material
Regional Governance in Divided Societies: Evidence from the Republic of Congo and Kenya
No full textReplication material
Synaptic NMDA receptor activity at resting membrane potentials
Full text linkNMDA receptors (NMDARs) are crucial for glutamatergic synaptic signaling in the mammalian central nervous system. When activated by glutamate and glycine/D-serine, the NMDAR ion channel can open, but current flux is further regulated by voltage-dependent block conferred by extracellular Mg(2+) ions. The unique biophysical property of ligand- and voltage-dependence positions NMDARs as synaptic coincidence detectors, controlling a major source of synaptic Ca(2+) influx. We measured synaptic currents in layer 2/3 neurons after stimulation in layer 4 of somatosensory cortex and found measurable NMDAR currents at all voltages tested. This NMDAR current did not require concurrent AMPAR depolarization. In physiological ionic conditions, the NMDAR current response at negative potentials was enhanced relative to ionic conditions typically used in slice experiments. NMDAR activity was also seen in synaptic recordings from hippocampal CA1 neurons, indicating a general property of NMDAR signaling. Using a fluorescent Ca(2+) indicator, we measured responses to stimulation in layer 4 at individual synaptic sites, and Ca(2+) influx could be detected even with AMPARs blocked. In current clamp recordings, we found that resting membrane potential was hyperpolarized by ∼7 mV and AP firing threshold depolarized by ∼4 mV in traditional compared to physiological ionic concentrations, and that NMDARs contribute to EPSPs at resting membrane potentials. These measurements demonstrate that, even in the presence of extracellular Mg(2+) and absence of postsynaptic depolarization, NMDARs contribute to synaptic currents and Ca(2+) influx
Synaptotagmin 7 sculpts short-term plasticity at a high probability synapse
No full textSynapses with high release probability (P
r
) tend to exhibit short-term synaptic depression. According to the prevailing model, this reflects the temporary depletion of release-ready vesicles after an initial action potential (AP). At the high-P
r
layer 4 to layer 2/3 (L4-L2/3) synapse in rodent somatosensory cortex, short-term plasticity appears to contradict the depletion model: depression is absent at interstimulus intervals (ISIs) less than 50 ms, and develops to a maximum at ∼200 ms. To understand the mechanism(s) underlying the biphasic time course of short-term plasticity at this synapse, we used whole-cell electrophysiology and two-photon calcium imaging in acute slices from male and female juvenile mice. We tested several candidate mechanisms including neuromodulation, postsynaptic receptor desensitization, and use-dependent changes in presynaptic AP-evoked calcium. We found that, at single L4-L2/3 synapses, P
r
varies as a function of ISI, giving rise to the distinctive short-term plasticity time course. Furthermore, the higher-than-expected P
r
at short ISIs depends on expression of synaptotagmin 7 (Syt7). Our results show that two distinct vesicle release processes summate to give rise to short-term plasticity at this synapse: i) a basal, high-P
r
release mechanism that undergoes rapid depression and recovers slowly (τ = ∼3 s); and ii) a Syt7-dependent mechanism that leads to a transient increase in P
r
(τ = ∼100 ms) after the initial AP. We thus reveal how these synapses can maintain a very high probability of neurotransmission for multiple APs within a short time frame.
Significance Statement
Release at single L4-L2/3 synapses violates a commonly held synaptic short-term plasticity rule. Although these synapses transmit with very high probability, they do not undergo profound short-term synaptic depression in the tens of milliseconds following an AP. Syt7 is a calcium-sensing protein important for synaptic facilitation and asynchronous release, but not previously known to play a role at high-P
r
synapses. We discovered that Syt7-mediated release shapes L4-L2/3 synaptic transmission by effectively counteracting short-term depression for ∼100 ms. We thus establish a molecular basis for a form of information processing at the synaptic level: the combination of these vesicle release properties results in a notch filter, preferentially conveying both very low and very high frequency signals
Extracellular glutamate is not modulated by cannabinoid receptor activity
Full text linkAbstract Cannabinoid receptor activation has been proposed to trigger glutamate release from astrocytes located in cortical layer 2/3. Here, we measure the basal concentration of extracellular glutamate in layer 2/3 of mouse somatosensory cortex and find it to be 20–30 nM. We further examine the effect of cannabinoid receptor signaling on extracellular glutamate, and find no evidence for increased extracellular glutamate upon cannabinoid receptor agonist application.Open-Access-Publikationsfonds 202
Incomplete block of NMDA receptors by intracellular MK-801
Full text linkNMDA receptors (NMDARs) are essential components in glutamatergic synaptic signaling. The NMDAR antagonist MK-801 has been a valuable pharmacological tool in evaluating NMDAR function because it binds with high affinity to the NMDAR ion channel pore and is non-competitive with ligand binding. MK-801 has also been used to selectively inhibit NMDAR current in only the cell being recorded by including the drug in the intracellular recording solution. Here, we report that intracellular MK-801 (iMK-801) only partially inhibits synaptic NMDAR currents at +40 mV at both cortical layer 4 to layer 2/3 and hippocampal Schaffer collateral to CA1 synapses. Furthermore, iMK-801 incompletely inhibits heterologously expressed NMDAR currents at -60 mV, consistent with a model of iMK-801 having a very slow binding rate and consequently ∼30,000 times lower affinity than MK-801 applied to the extracellular side of the receptor. While iMK-801 can be used as a qualitative tool to study reduced postsynaptic NMDAR function, it cannot be assumed to completely block NMDARs at concentrations typically used in experiments
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
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