Role of dorsomedial striatum neuronal ensembles in incubation of methamphetamine craving after voluntary abstinence

Abstract We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. SIGNIFICANCE STATEMENT: In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we used classical pharmacology, in situ hybridization, immunohistochemistry, and the Daun02 inactivation procedure to demonstrate a critical role of dorsomedial striatum neuronal ensembles in this new form of incubation of drug craving

Application of Distributed Fiber Optic Strain Sensors to LMQXFA Cold Mass Welding

The future High Luminosity upgrade of the Large Hadron Collider (HL-LHC) at CERN will include the low-beta inner triplets (Q1, Q2a/b, Q3) for two LHC insertion regions. The Q1, Q3 components consist of eight 10 m-long LMQXFA cryo-assemblies fabricated by the HL-LHC Accelerator Upgrade Project. Each LMQXFA Cold mass contains two Nb3Sn magnets connected in series. A stainless-steel shell is welded around the two magnets before the insertion into the cryostat. There is a limit on how much coil preload increase induced by the shell welding is allowed. Distributed Rayleigh backscattering fiber optics sensors were used for the first time to obtain a strain map over a wide area of a Nb3Sn magnet cold mass shell. Data were collected during welding of the first LMQXFA cold mass and the results confirm that the increase of the coil pole azimuthal pre-stress after welding do not exceed requirements

Examining decentralization and managerial decision making for child immunization program performance in India

Despite widespread adoption of decentralization reforms, the impact of decentralization on health system attributes, such as access to health services, responsiveness to population health needs, and effectiveness in affecting health outcomes, remains unclear. This study examines how decision space, institutional capacities, and accountability mechanisms of the Intensified Mission Indradhanush (IMI) in India relate to measurable performance of the immunization program. Data on decision space and its related dimensions of institutional capacity and accountability were collected by conducting structured interviews with managers based in 24 districts, 61 blocks, and 279 subcenters. Two measures by which to assess performance were selected: (1) proportion reduction in the DTP3 coverage gap (i.e., effectiveness), and (2) total IMI doses delivered per incremental USD spent on program implementation (i.e., efficiency). Descriptive statistics on decision space, institutional capacity, and accountability for IMI managers were generated. Structural equation models (SEM) were specified to detect any potential associations between decision space dimensions and performance measures. The majority of districts and blocks indicated low levels of decision space. Institutional capacity and accountability were similar across areas. Increases in decision space were associated with less progress towards closing the immunization coverage gap in the IMI context. Initiatives to support health workers and managers based on their specific contextual challenges could further improve outcomes of the program. Similar to previous studies, results revealed strong associations between each of the three decentralization dimensions. Health systems should consider the impact that management structures have on the efficiency and effectiveness of health services delivery. Future research could provide greater evidence for directionality of direct and indirect effects, interaction effects, and/or mediators of relationships

Distinct fos-expressing neuronal ensembles in the ventromedial prefrontal cortex mediate food reward and extinction memories

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration.Wefirst trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area

Fos-expressing neuronal ensemble in rat ventromedial prefrontal cortex encodes cocaine seeking but not food seeking in rats

Neuronal ensembles in ventromedial prefrontal cortex (vmPFC) play a role in both cocaine and palatable food seeking. However, it is unknown whether similar or different vmPFC neuronal ensembles mediate food and cocaine seeking. Here, we used the Daun02 inactivation procedure to assess whether the neuronal ensembles mediating food and cocaine seeking can be functionally distinguished. We trained male and female Fos-LacZ rats to self-administer palatable food pellets and cocaine on alternating days for 18 days. We then exposed the rats to a brief nonreinforced food- or cocaine-seeking test to induce Fos and β-gal in neuronal ensembles associated with food or cocaine seeking, respectively and infused Daun02 into vmPFC to ablate the β-gal-expressing ensembles. Two days later, we tested the rats for food or cocaine seeking under extinction conditions. Although inactivation of the food-seeking ensemble did not influence food or cocaine seeking, inactivation of the cocaine-seeking ensemble reduced cocaine seeking but not food seeking. Results indicate that the neuronal ensemble activated by cocaine seeking in vmPFC is functionally separate from the ensemble activated by food seeking

Insertion Magnets

Chapter 3 in High-Luminosity Large Hadron Collider (HL-LHC) : Preliminary Design Report. The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new energy frontier for exploration in 2010, it has gathered a global user community of about 7,000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its luminosity (rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total collisions created) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this upgrade must be carefully conceived and will require about ten years to implement. The new configuration, known as High Luminosity LHC (HL-LHC), will rely on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11-12 tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 300 metre-long high-power superconducting links with negligible energy dissipation. The present document describes the technologies and components that will be used to realise the project and is intended to serve as the basis for the detailed engineering design of HL-LHC.Comment: 19 pages, Chapter 3 in High-Luminosity Large Hadron Collider (HL-LHC) : Preliminary Design Repor