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Schizophrenia is associated with impaired attention. The top-down control of attention, defined as the ability to guide and refocus attention in accordance with internal goals and representations, was identified by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative as an important construct for task development and research. A recent CNTRICS meeting identified three tasks commonly used with rodent models as having high construct validity and promise for further development: The 5-choice serial reaction time task, the 5-choice continuous performance task, and the distractor condition sustained attention task. Here we describe their current status, including data on their neural substrates, evidence for sensitivity to neuropharmacological manipulations and genetic influences, and data from animal models of the cognitive deficits of schizophrenia. A common strength is the development of parallel human tasks to facilitate connections to the neural circuitry and drug development research done in these animal models. We conclude with recommendations for the steps needed to improve testing so that it better represents the complex biological and behavioral picture presented by schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: The ongoing evolution of BCG after its introduction in 1921 resulted in strains that differ genetically and phenotypically. Based on a genomic deletion (Region of Difference 2 or RD2) that occurred between 1927 and 1931, BCG strains can be sub-classified by the presence or absence of RD2. The existence of other mutations that distinguish BCG strains precludes simple comparison of RD2-positive and RD2-negative BCG strains to determine the importance, if any, of RD2 for vaccine protection. In this study, we have compared the RD2-containing BCG Russia, BCG Pasteur (which is a natural mutant for RD2), and BCG Pasteur complemented with RD2-genes Rv1979c-Rv1982 through various in vitro and in vivo assays of immunogenicity and protection. We determined that the presence of RD2 did not affect vaccine persistence, but lead to increased immunogenicity, as measured by ELISpot. Additionally, T-cells from animals immunized with BCG Russia and BCG Pasteur::Rv1979c-82 were more effective at killing Mycobacterium tuberculosis in macrophages than T-cells from animals immunized with BCG Pasteur. In a mouse vaccine-challenge model, the presence of RD2 had no effect on pulmonary TB, as measured by M. tuberculosis burden and degree of histopathology, at 4, 8 or 12 weeks post-infection. The presence of RD2 was however associated with decreased dissemination of M. tuberculosis to the spleen. Together, our data demonstrated that the loss of RD2 resulted in decreased immunogenicity but did not affect protection against pulmonary TB, indicating a dissociation between these phenotypes associated with BCG vaccination. [Copyright &y& Elsevier]

The aim of the present experiment was to determine the influence of nutritional manipulations during early life on feeding regulatory mechanisms. For this purpose, neuropeptide Y (NPY) release in the hypothalamic paraventricular nucleus was measured in male offspring born to dams fed either on a control (C) diet, on a high-carbohydrate (HC) diet or on a high-fat (HF) diet during gestation and lactation periods. In addition, we examined the development of dietary preferences in these rats. NPY release was measuredin vivothrough the push–pull technique after a stimulation with 2-deoxy-glucose (2DG), a blocker of carbohydrate metabolism. NPY release was significantly enhanced in the HC rats after 2DG (+89% vs. control and +54% vs. HF rats;P < 0.01). In a two-bottle choice test, a clear preference for carbohydrate (62% vs. 38%;P < 0.01) was present as early as 30 days of age in control rats. The establishment of this preference in HC and HF rats was delayed by 2 and 3 months, respectively. Therefore, each type of dietary manipulation during early life has left a specific imprint in the offspring. The change in reactivity of the NPY system to glucopenia persisted in adulthood. When combined with the early changes in the dietary preferences, this can lead to adverse effects on body weight when abundant and palatable food is offered. These data support the hypothesis of an intrauterine and perinatalprogramming of the central regulatory mechanisms and reinforce the necessity of a preventive approach for the treatment of obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

In the present study, the onset of thermal convection in a liquid layer overlying a porous layer in the presence of a free surface with evaporation is investigated. The non-linear two-dimensional Navier–Stokes equation along with the energy equation is solved for the liquid layer. The Brinkman model with the energy equation describes the porous layer. The partial differential equations are solved numerically using the finite element technique. At the free surface, two conditions are treated simultaneously. The surface tension is assumed to vary linearly with temperature, therefore the existence of Marangoni convection. The second condition assumes that evaporation takes place at the free surface. With the cavity heated laterally, it is found that the switching of the flow from the liquid layer into the porous layer is due to the ratio of the liquid thickness to the porous thickness, designated as thickness ratio. Different aspect ratios, thickness ratios as well as saturation temperatures are also studied in detail for the pure thermocapillary case. Results reveal the importance evaporation at the free surface has on convection patterns in the cavity. [Copyright &y& Elsevier]

Focuses on the results of a study measuring the release of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus in rats through push-pull technique. Peak of NPY release; Comparison of feeding behavior between lean and obese rats.

Focuses on the measurement of neuropeptide Y (NPY) release in the paraventricular nucleus (PVN) of unrestrained rats through the push-pull technique. How NPY release was augmented; Indication that NPY release could drive feeding behavior in the normal life; Discussion on results of study.

The formation of a structured behavioral motor response to an external painful (nociceptive) stimulus is performed in certain cerebral neuronal networks (NNs), and this is related to specific mental phenomena (experience of pain, mental pain images). We state that the description of the respective NNs (a biologically expedient pain neuromatrix) is impossible without taking into account mental pain-related phenomena. Structural and functional features of the respective NNs, responsible for the performance of pain-related behavior, are discussed. The specificities of functioning of definite synapses in the process of regulation of such behavior are also discussed. In fact, the proposed article deals with functional (as well as causal) relationships between objective and subjective processes providing the formation of novel information in the brain; this complex process is based on the integration of the earlier experience in the brain in the course of formation of a "competent" (expedient, structured by the above experience) motor act. [ABSTRACT FROM AUTHOR]

Abstract: Behavioral and neuronal abnormalities observed in mice exhibiting a reduced expression of the dopamine transporter model important aspects of schizophrenia, addiction, and attentional disorders. As the consequences of a chronic hyperdopaminergic tone for striatal output regulation have remained poorly understood, the present experiments were designed to determine the status of striatal interneuronal cholinergic neurotransmission in dopamine transporter knockdown animals. The high-affinity choline transporter represents the rate-limiting step of acetylcholine synthesis and release. Compared with wild type mice, striatal high-affinity choline transporter expression in dopamine transporter knockdown mice was significantly decreased. As in vivo basal striatal acetylcholine release did not differ between the strains, reduced high-affinity choline transporter expression in dopamine transporter knockdown mice was not due to reduced basal cholinergic activity. Furthermore, the proportion of high-affinity choline transporters expressed in plasma membrane-enriched versus vesicular membrane-enriched fractions did not differ from wild type animals, suggesting that changes in intracellular high-affinity choline transporter trafficking were not associated with lower overall levels of striatal high-affinity choline transporters. Synaptosomal choline uptake assays indicated a reduced capacity of striatal high-affinity choline transporters in dopamine transporter knockdown mice, and thus the functional significance of the reduced level of high-affinity choline transporter expression. Likewise, in vivo measures of the capacity of striatal high-affinity choline transporters to clear increases in extracellular choline concentrations, using choline-sensitive microelectrodes, revealed a 37–41% reduction in hemicholinium-sensitive clearance of exogenous choline in dopamine transporter knockdown mice. Furthermore, clearance of potassium-evoked choline signals was reduced in dopamine transporter knockdown mice (1.63±0.15 μM/s) compared with wild type animals (2.29±0.21 μM/s). Dysregulated striatal cholinergic neurotransmission is hypothesized to disrupt the integration of thalamic and cortical information at spiny projection neurons and thus to contribute to abnormal striatal information processing in dopamine transporter knockdown mice. [Copyright &y& Elsevier]

Adrenergic nerves innervate the human cerebrovasculature, yet the functional role of neurogenic influences on cerebral hemodynamics remains speculative. In the current study, regional cerebrovascular responses to sympathoexcitatory reflexes were evaluated. In eight volunteers, contrast-enhanced computed tomography was performed at baseline, −40 mmHg lower body negative pressure (LBNP), and a cold pressor test (CPT). Cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF) were evaluated in cortical gray matter (GM), white matter (WM), and basal ganglia/thalamus (BGT) regions. Lower body negative pressure resulted in tachycardia and decreased central venous pressure while mean arterial pressure was maintained. Cold pressor test resulted in increased mean arterial pressure concomitant with tachycardia but no change in central venous pressure. Neither reflex altered end-tidal carbon dioxide. Cerebral blood volume was reduced in GM during both LBNP and CPT (P<0.05) but was unchanged in WM and BGT. Mean transit time was reduced in WM and GM during CPT (P<0.05). Cerebral blood flow was only modestly affected with either reflex (P<0.07). The combined reductions in GM CBV (∼−25%) and MTT, both with and without any change in central venous pressure, with small CBF changes (∼−11%), suggest that active venoconstriction contributed to the volume changes. These data demonstrate that CBV is reduced during engagement of sympathoexcitatory reflexes and that these cerebrovascular changes are heterogeneously distributed.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 136–143. doi:10.1038/sj.jcbfm.9600015 [ABSTRACT FROM AUTHOR]