Dorsal-CA1 hippocampal neuronal ensembles encode nicotine-reward contextual associations

Natural and drug rewards increase the motivational valence of stimuli in the environment that, through Pavlovian learning mechanisms, become conditioned stimuli that directly motivate behavior in the absence of the original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca2+ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and that are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference

Stress-induced reinstatement of nicotine preference requires dynorphin/kappa opioid activity in the basolateral amygdala

UNLABELLED: The dynorphin (DYN)/kappa-opioid receptor (KOR) system plays a conserved role in stress-induced reinstatement of drug seeking for prototypical substances of abuse. Due to nicotine\u27s high propensity for stress-induced relapse, we hypothesized that stress would induce reinstatement of nicotine seeking-like behavior in a KOR-dependent manner. Using a conditioned place preference (CPP) reinstatement procedure in mice, we show that both foot-shock stress and the pharmacological stressor yohimbine (2 mg/kg, i.p.) induce reinstatement of nicotine CPP in a norbinaltorphimine (norBNI, a KOR antagonist)-sensitive manner, indicating that KOR activity is necessary for stress-induced nicotine CPP reinstatement. After reinstatement testing, we visualized robust c-fos expression in the basolateral amygdala (BLA), which was reduced in mice pretreated with norBNI. We then used several distinct but complementary approaches of locally disrupting BLA KOR activity to assess the role of KORs and KOR-coupled intracellular signaling cascades on reinstatement of nicotine CPP. norBNI injected locally into the BLA prevented yohimbine-induced nicotine CPP reinstatement without affecting CPP acquisition. Similarly, selective deletion of BLA KORs in KOR conditional knock-out mice prevented foot-shock-induced CPP reinstatement. Together, these findings strongly implicate BLA KORs in stress-induced nicotine seeking-like behavior. In addition, we found that chemogenetic activation of Gαi signaling within CaMKIIα BLA neurons was sufficient to induce nicotine CPP reinstatement, identifying an anatomically specific intracellular mechanism by which stress leads to reinstatement. Considered together, our findings suggest that activation of the DYN/KOR system and Gαi signaling within the BLA is both necessary and sufficient to produce reinstatement of nicotine preference. SIGNIFICANCE STATEMENT: Considering the major impact of nicotine use on human health, understanding the mechanisms by which stress triggers reinstatement of drug-seeking behaviors is particularly pertinent to nicotine. The dynorphin (DYN)/kappa-opioid receptor (KOR) system has been implicated in stress-induced reinstatement of drug seeking for other commonly abused drugs. However, the specific role, brain region, and mechanisms that this system plays in reinstatement of nicotine seeking has not been characterized. Here, we report region-specific engagement of the DYN/KOR system and subsequent activation of inhibitory (Gi-linked) intracellular signaling pathways within the basolateral amygdala during stress-induced reinstatement of nicotine preference. We show that the DYN/KOR system is necessary to produce this behavioral state. This work may provide novel insight for the development of therapeutic approaches to prevent stress-related nicotine relapse

p-GaAs nanowire MESFETs with near-thermal limit gating

Difficulties in obtaining high-performance p-type transistors and gate insulator charge-trapping effects present two major challenges for III-V complementary metal-oxide semiconductor (CMOS) electronics. We report a p-GaAs nanowire metal-semiconductor field-effect transistor (MESFET) that eliminates the need for a gate insulator by exploiting the Schottky barrier at the metal-GaAs interface. Our device beats the best-performing p-GaSb nanowire metal-oxide-semiconductor field effect transistor (MOSFET), giving a typical sub-threshold swing of 62 mV/dec, within 4% of the thermal limit, on-off ratio $\sim 10^{5}$, on-resistance ~700 k$\Omega$, contact resistance ~30 k$\Omega$, peak transconductance 1.2 $\mu$S/$\mu$m and high-fidelity ac operation at frequencies up to 10 kHz. The device consists of a GaAs nanowire with an undoped core and heavily Be-doped shell. We carefully etch back the nanowire at the gate locations to obtain Schottky-barrier insulated gates whilst leaving the doped shell intact at the contacts to obtain low contact resistance. Our device opens a path to all-GaAs nanowire MESFET complementary circuits with simplified fabrication and improved performance

Transport and Strong-Correlation Phenomena in Carbon Nanotube Quantum Dots in a Magnetic Field

Transport through carbon nanotube (CNT) quantum dots (QDs) in a magnetic field is discussed. The evolution of the system from the ultraviolet to the infrared is analyzed; the strongly correlated (SC) states arising in the infrared are investigated. Experimental consequences of the physics are presented -- the SC states arising at various fillings are shown to be drastically different, with distinct signatures in the conductance and, in particular, the noise. Besides CNT QDs, our results are also relevant to double QD systems.Comment: 5 pages, 5 figure

Migrating to Cloud-Native Architectures Using Microservices: An Experience Report

Migration to the cloud has been a popular topic in industry and academia in recent years. Despite many benefits that the cloud presents, such as high availability and scalability, most of the on-premise application architectures are not ready to fully exploit the benefits of this environment, and adapting them to this environment is a non-trivial task. Microservices have appeared recently as novel architectural styles that are native to the cloud. These cloud-native architectures can facilitate migrating on-premise architectures to fully benefit from the cloud environments because non-functional attributes, like scalability, are inherent in this style. The existing approaches on cloud migration does not mostly consider cloud-native architectures as their first-class citizens. As a result, the final product may not meet its primary drivers for migration. In this paper, we intend to report our experience and lessons learned in an ongoing project on migrating a monolithic on-premise software architecture to microservices. We concluded that microservices is not a one-fit-all solution as it introduces new complexities to the system, and many factors, such as distribution complexities, should be considered before adopting this style. However, if adopted in a context that needs high flexibility in terms of scalability and availability, it can deliver its promised benefits

Maternal Undernourishment in Guinea Pigs Leads to Fetal Growth Restriction with Increased Hypoxic Cells and Oxidative Stress in the Brain.

BACKGROUND: We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for brain hypoxia and oxidative stress. METHODS: Guinea pigs were fed ad libitum (control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1) was injected into pregnant sows. Fetuses were then necropsied and brain tissues were processed for HP-1 (hypoxia marker) and 4HNE, 8-OHdG, and 3-nitrotyrosine (oxidative stress markers) immunoreactivity (IR). RESULTS: FGR-MNR fetal and brain weights were decreased 38 and 12%, respectively, with brain/fetal weights thereby increased 45% as a measure of brain sparing, and more so in males than females. FGR-MNR HP-1 IR was increased in most of the brain regions studied, and more so in males than females, while 4HNE and 8-OHdG IR were increased in select brain regions, but with no sex differences. CONCLUSIONS: Chronic hypoxia is likely to be an important signaling mechanism in the FGR brain, but with males showing more hypoxia than females. This may involve sex differences in adaptive decreases in growth and normalizing of oxygen, with implications for sex-specific alterations in brain development and risk for later neuropsychiatric disorder

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

Motor Nucleus of Vagus---Location. Methods supplementary material: Neuroanatomical approach to locating vagal motor nucleus in fetal sheep brain (PDF 1716 kb

Raman spectroscopy and electrical properties of InAs nanowires with local oxidation enabled by substrate micro-trenches and laser irradiation

The thermal gradient along indium-arsenide nanowires was engineered by a combination of fabricated micro- trenches in the supporting substrate and focused laser irradiation. This allowed local control of thermally activated oxidation reactions of the nanowire on the scale of the diffraction limit. The locality of the oxidation was detected by micro-Raman mapping, and the results were found consistent with numerical simulations of the temperature profile. Applying the technique to nanowires in electrical devices the locally oxidized nanowires remained conducting with a lower conductance as expected for an effectively thinner conducting core

Anisotropic Pair Correlations and Structure Factors of Confined Hard-Sphere Fluids: An Experimental and Theoretical Study

We address the fundamental question: how are pair correlations and structure factors of hard-sphere fluids affected by confinement between hard planar walls at close distance? For this purpose, we combine x-ray scattering from colloid-filled nanofluidic channel arrays and first-principles inhomogeneous liquid-state theory within the anisotropic Percus-Yevick approximation. The experimental and theoretical data are in remarkable agreement at the pair-correlation level, providing the first quantitative experimental verification of the theoretically predicted confinement-induced anisotropy of the pair-correlation functions for the fluid. The description of confined fluids at this level provides, in the general case, important insights into the mechanisms of particle-particle interactions in dense fluids under confinement