Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats

Rationale Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Objectives Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. Methods The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. Results We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. Conclusions These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control

GEANT4 : a simulation toolkit

Abstract Geant4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics. PACS: 07.05.Tp; 13; 2

Differential Encoding of Factors Influencing Predicted Reward Value in Monkey Rostral Anterior Cingulate Cortex

Background: The value of a predicted reward can be estimated based on the conjunction of both the intrinsic reward value and the length of time to obtain it. The question we addressed is how the two aspects, reward size and proximity to reward, influence the responses of neurons in rostral anterior cingulate cortex (rACC), a brain region thought to play an important role in reward processing. Methods and Findings: We recorded from single neurons while two monkeys performed a multi-trial reward schedule task. The monkeys performed 1–4 sequential color discrimination trials to obtain a reward of 1–3 liquid drops. There were two task conditions, a valid cue condition, where the number of trials and reward amount were associated with visual cues, and a random cue condition, where the cue was picked from the cue set at random. In the valid cue condition, the neuronal firing is strongly modulated by the predicted reward proximity during the trials. Information about the predicted reward amount is almost absent at those times. In substantial subpopulations, the neuronal responses decreased or increased gradually through schedule progress to the predicted outcome. These two gradually modulating signals could be used to calculate the effect of time on the perception of reward value. In the random cue condition, little information about the reward proximity or reward amount is encoded during the course of the trial before reward delivery, but when the reward is actually delivered the responses reflect both the reward proximity and reward amount

GEANT4--a simulation toolkikt

Geant4 is a toolkit for simulating the passage of particles through matter. It includes a complete range of functionality including tracking, geometry, physics models and hits. The physics processes offered cover a comprehensive range, including electromagnetic, hadronic and optical processes, a large set of long-lived particles, materials and elements, over a wide energy range starting, in some cases, from 250 eV and extending in others to the TeV energy range. It has been designed and constructed to expose the physics models utilised, to handle complex geometries, and to enable its easy adaptation for optimal use in different sets of applications. The toolkit is the result of a worldwide collaboration of physicists and software engineers. It has been created exploiting software engineering and object-oriented technology and implemented in the C++ programming language. It has been used in applications in particle physics, nuclear physics, accelerator design, space engineering and medical physics

Plasma Sex Steroid Levels and Steroidogenesis in the Gonad of the Self-fertilizing Fish Rivulus marmoratus

The mangrove killifish, Rivulus marmoratus, is the only known self-fertilizing vertebrate. This species is sexually dimorphic; sexually mature individuals are either hermaphrodite or primary and secondary males. Although the mangrove killifish has a unique reproductive strategy, there has been no study on the reproductive endocrinology of this species. Thus we investigated plasma sex steroid hormone levels and steroidogenesis in the gonads of R. marmoratus by enzyme linked immunosorbent assay (ELISA). Plasma 17β-estradiol (E2) and 11-ketotestosterone (11-KT) were detected both in hermaphrodite and in primary male. Ovarian follicles (follicle-enclosed oocytes) from hermaphrodites, which were categorized into early yolk stage and late yolk stage, and testis tissue of primary males were cultured with different concentrations of 17α-hydroxyprogesterone (OHP) or testosterone (T) for 24 h. Production of T, E2, 11-KT and 17α-20 β-dihydroxy-4-pregnen-3-one (17α,20β-P) in the medium from tissue culture were measured by ELISA. Early and late ovarian follicles of hermaphrodites and testis pieces of primary males synchronously secreted E2, 11-KT, and 17α,20β-P following incubation with OHP or T. We conclude that both hermaphrodite and primary male of the mangrove killifish secrete estrogen, androgen, and progestin synchronously

Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

The chemogenetic technology designer receptors exclusively activated by designer drugs (DREADDs) afford remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities and potential off-target effects of CNO represent areas for improvement. Here, we provide a new high-affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg per kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg per kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents a potent, selective, metabolically stable and fast-acting DREADD agonist with utility in both mice and nonhuman primates for a variety of applications

Differences in life-history traits in two clonal strains of the self-fertilizing fish, Rivulus marmoratus

We compared life-history traits such as fecundity, sex ratio, reproductive cycle, age at sexual maturity, embryonic period, egg size, early growth and morphology in two clonal strains (PAN-RS and DAN) of the mangrove killifish, Rivulus marmoratus, under constant rearing conditions. We found a positive relationship between growth and reproductive effort. Fecundity was significantly higher in the PAN-RS strain than in the DAN strain. The sex ratio was significantly different, with DAN producing more primary males than PAN-RS. Spawning and ovulation cycle did not clearly differ between the strains. PAN-RS showed a significantly higher growth rate than DAN from 0 to 100 days after hatching, however, age at sexual maturity, embryonic period, egg size, and morphometric and meristic characteristics (vertebral and fin-ray counts) did not differ between the two strains. The high fecundity of PAN-RS may provide an increased chance of offspring survival, while the attainment of sexual maturity at a smaller size in DAN may allow them to invest earlier in reproduction to increase breeding success. Variations in the life-history traits of PAN-RS and DAN may be adaptive strategies for life in their natural habitat, which consists of mangrove estuaries with a highly variable environment