Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
2,132
result(s) for
"Smith, W. C."
Sort by:
Reinstatement of nicotine seeking is mediated by glutamatergic plasticity
Nicotine abuse and addiction is a major health liability. Nicotine, an active alkaloid in tobacco, is self-administered by animals and produces cellular adaptations in brain regions associated with drug reward, such as the nucleus accumbens. However, it is unknown whether, akin to illicit drugs of abuse such as cocaine or heroin, the adaptations endure and contribute to the propensity to relapse after discontinuing nicotine use. Using a rat model of cue-induced relapse, we made morphological and electrophysiological measures of synaptic plasticity, as well as quantified glutamate overflow, in the accumbens after 2 wk of withdrawal with extinction training. We found an enduring basal increase in dendritic spine head diameter and in the ratio of AMPA to NMDA currents in accumbens spiny neurons compared with yoked saline animals at 2 wk after the last nicotine self-administration session. This synaptic potentiation was associated with an increase in both AMPA (GluA1) and NMDA (GluN2A and GluN2B) receptor subunits, and a reduction in the glutamate transporter-1 (GLT-1). When nicotine seeking was reinstated by presentation of conditioned cues, there were parallel increases in behavioral responding, extracellular glutamate, and further increases in dendritic spine head diameter and ratio of AMPA to NMDA currents within 15 min. These findings suggest that targeting glutamate transmission might inhibit cue-induced nicotine seeking. In support of this hypothesis, we found that pharmacological inhibition of GluN2A with 3-Chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl]benzyl]benzenesulfonamide (TCN-201) or GluN2B with ifenprodil abolished reinstated nicotine seeking. These results indicate that up-regulated GluN2A, GluN2B, and rapid synaptic potentiation in the accumbens contribute to cue-induced relapse to nicotine use.
Journal Article
Spectral signature of high-order photon processes enhanced by Cooper-pair pairing
Inducing interactions between individual photons is key for photonic quantum information and studying many-body photon states. Superconducting circuits are well suited to combine strong interactions with low losses. Typically, microwave photons are stored in an
L
C
oscillator shunted by a Josephson junction, where the zero-point phase fluctuations across the junction determine the strength and order of photon interactions. Most superconducting nonlinear oscillators operate with small phase fluctuations, where two-photon Kerr interactions dominate. In our experiment, we shunt a high-impedance
L
C
oscillator with a dipole element favoring the tunneling of paired Cooper pairs. This leads to large phase fluctuations of 3.4, accessing a regime where transition frequencies shift non-monotonically with excitation number. From spectroscopy, we extract two-, three-, and four-photon interaction energies, all of similar strength and exceeding the photon loss rate. Our results open a new regime of high-order photon interactions in microwave quantum optics.
In superconducting circuits, the nonlinearity of Josephson junctions mediates photon interactions, but they are typically dominated by two-photon processes. Here the authors observe multi-photon interactions in a superconducting circuit with Cooper-pair pairing, revealing a new regime of microwave quantum optics.
Journal Article
Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions
Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions.
New instrumental learning occurs through an unexpected delivery of a rewarding stimulus or the withdrawal of a punishing stimulus. The authors show that D1 receptor-expressing medium spiny neurons (MSNs) in the anterior dorsolateral striatum encode newly learned instrumental actions whereas D2 MSNs promote the expression of habitual actions.
Journal Article
Magnifying Quantum Phase Fluctuations with Cooper-Pair Pairing
Remarkably, complex assemblies of superconducting wires, electrodes, and Josephson junctions are compactly described by a handful of collective phase degrees of freedom that behave like quantum particles in a potential. Almost all these circuits operate in the regime where quantum phase fluctuations are small—the associated flux is smaller than the superconducting flux quantum—although entering the regime of large fluctuations would have profound implications for metrology and qubit protection. The difficulty arises from the apparent need for circuit impedances vastly exceeding the resistance quantum. Independently, exotic circuit elements that require Cooper pairs to form pairs in order to tunnel have been developed to encode and topologically protect quantum information. In this work, we demonstrate that pairing Cooper pairs magnifies the phase fluctuations of the circuit ground state. We measure a tenfold suppression of flux sensitivity of the first transition energy only, implying a twofold increase in the vacuum phase fluctuations and showing that the ground state is delocalized over several Josephson wells.
Journal Article
Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells
The splicing factor
SF3B1
is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of
SF3B1
disruption in myeloid cell lines:
SF3B1
knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34
+
cells from MDS patients with
SF3B1
mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in
SF3B1
mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (
ASXL1
and
CBL
), iron homeostasis and mitochondrial metabolism (
ALAS2, ABCB7
and
SLC25A37
) and RNA splicing/processing (
PRPF8
and
HNRNPD
). Many genes regulated by a DNA damage-induced BRCA1–BCLAF1–SF3B1 protein complex showed differential expression/splicing in
SF3B1
mutant cases. This is the first study to determine the target genes of
SF3B1
mutation in MDS CD34
+
cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.
Journal Article
Fluxonium-Based Artificial Molecule with a Tunable Magnetic Moment
Engineered quantum systems allow us to observe phenomena that are not easily accessible naturally. The LEGO®-like nature of superconducting circuits makes them particularly suited for building and coupling artificial atoms. Here, we introduce an artificial molecule, composed of two strongly coupled fluxonium atoms, which possesses a tunable magnetic moment. Using an applied external flux, one can tune the molecule between two regimes: one in which the ground-excited state manifold has a magnetic dipole moment and one in which the ground-excited state manifold has only a magnetic quadrupole moment. By varying the applied external flux, we find the coherence of the molecule to be limited by local flux noise. The ability to engineer and control artificial molecules paves the way for building more complex circuits for quantum simulation and protected qubits.
Journal Article
Temporal and radial variation of the solar wind temperature-speed relationship
The solar wind temperature (T) and speed (V) are generally well correlated at ∼1 AU, except in Interplanetary Coronal Mass Ejections where this correlation breaks down. We perform a comprehensive analysis of both the temporal and radial variation in the temperature‐speed (T‐V) relationship of the non‐transient wind, and our analysis provides insight into both the causes of the T‐V relationship and the sources of the temperature variability. Often at 1 AU the speed‐temperature relationship is well represented by a single linear fit over a speed range spanning both the slow and fast wind. However, at times the fast wind from coronal holes can have a different T‐V relationship than the slow wind. A good example of this was in 2003 when there was a very large and long‐lived outward magnetic polarity coronal hole at low latitudes that emitted wind with speeds as fast as a polar coronal hole. The long‐lived nature of the hole made it possible to clearly distinguish that some holes can have a different T‐V relationship. In an earlier ACE study, we found that both the compressions and rarefactions T‐V curves are linear, but the compression curve is shifted to higher temperatures. By separating compressions and rarefactions prior to determining the radial profiles of the solar wind parameters, the importance of dynamic interactions on the radial evolution of the solar wind parameters is revealed. Although the T‐V relationship at 1 AU is often well described by a single linear curve, we find that the T‐V relationship continually evolves with distance. Beyond ∼2.5 AU the differences between the compressions and rarefactions are quite significant and affect the shape of the overall T‐V distribution to the point that a simple linear fit no longer describes the distribution well. Since additional heating of the ambient solar wind outside of interaction regions can be associated with Alfvénic fluctuations and the turbulent energy cascade, we also estimate the heating rate radial profile from the solar wind speed and temperature measurements. Key Points Solar wind speed‐temperature relationship systematically evolves with distance There is an overall decrease in the T‐V slope since 1972 In 2003 a long‐lived coronal hole extension emitted atypically fast wind
Journal Article