12 research outputs found

    Relative contributions and mapping of ventral tegmental area dopamine and GABA neurons by projection target in the rat

    No full text
    The ventral tegmental area (VTA) is a heterogeneous midbrain structure that contains dopamine (DA), GABA, and glutamate neurons that project to many different brain regions. Here, we combined retrograde tracing with immunocytochemistry against tyrosine hydroxylase (TH) or glutamate decarboxylase (GAD) to systematically compare the proportion of dopaminergic and GABAergic VTA projections to 10 target nuclei: anterior cingulate, prelimbic, and infralimbic cortex; nucleus accumbens core, medial shell, and lateral shell; anterior and posterior basolateral amygdala; ventral pallidum; and periaqueductal gray. Overall, the non-dopaminergic component predominated VTA efferents, accounting for more than 50% of all projecting neurons to each region except the nucleus accumbens core. In addition, GABA neurons contributed no more than 20% to each projection, with the exception of the projection to the ventrolateral periaqueductal gray, where the GABAergic contribution approached 50%. Therefore, there is likely a significant glutamatergic component to many of the VTA's projections. We also found that VTA cell bodies retrogradely labeled from the various target brain regions had distinct distribution patterns within the VTA, including in the locations of DA and GABA neurons. Despite this patterned organization, VTA neurons comprising these different projections were intermingled and never limited to any one subregion. These anatomical results are consistent with the idea that VTA neurons participate in multiple distinct, parallel circuits that differentially contribute to motivation and reward. While attention has largely focused on VTA DA neurons, a better understanding of VTA subpopulations, especially the contribution of non-DA neurons to projections, will be critical for future work5275916941sem informaçãosem informaçã

    Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis

    No full text
    Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined factors. R-spondin 3 (RSPO3) is one of the most potent enhancers of Wnt signaling and its expression is usually restricted to the stem cell niche where it provides localized enhancement of Wnt signaling to regulate stem cell expansion and differentiation. Disruption of this niche-confined expression can disturb proper tissue organization and lead to cancers. Here, we investigate the consequences of disrupting the niche restricted expression of RSPO3 in various tissues including the hematopoietic system. We show that normal Rspo3 expression is confined to the perivascular niche in the bone marrow. Induction of increased systemic levels of circulating RSPO3 outside of the niche results in prominent loss of early-B cell progenitors and anemia but surprisingly has no effect on hematopoietic stem cells (HSCs). Using molecular, pharmacological and genetic approaches, we demonstrate that these RSPO3-induced hematopoietic phenotypes are Wnt and RSPO3 dependent and mediated through non-canonical Wnt signaling. Our study highlights a distinct role for a Wnt/RSPO3 signaling axis in the regulation of hematopoiesis, as well as possible challenges related to therapeutic usage of R-spondins for regenerative medicine

    Expectations Traps and Monetary Policy with Limited Commitment

    Get PDF
    We study the existence and uniqueness properties of monetary policy with limited commitment in LQ RE models. We use a New Keynesian model with debt accumulation in the spirit of Leeper (1991) as a 'lab', because this model generates multiple equilibria under pure discretion, and under full commitment there are two distinct determinate regimes. We study how these properties change over the continuum of intermediate cases between commitment and discretion. We find that although multiple equilibria exist for high degrees of precommitment, even a small degree of precommitment selects a unique equilibrium for a wide range of parameters. We discuss the stability properties of policy equilibria which can be used to design an equilibrium selection criterion. We also demonstrate very different welfare implications for different policy equilibria

    The Interest Rate - Exchange Rate Nexus: Exchange Rate Regimes and Policy Equilibria

    No full text
    We study a credible Markov-perfect monetary policy in an open New Keynesian economy with incomplete financial markets. We demonstrate the existence of two discretionary equilibria. Following a shock the economy can be stabilised either 'quickly' or 'slow', both dynamic paths satisfy conditions of optimality and time-consistency. The model can help us to understand sudden change of the interest rate and exchange rate volatility in 'tranquil' and 'volatile' regimes even under a fully credible 'soft peg' of the nominal exchange rate in developing countries

    Engineering Human Brain Organoids: From Basic Research to Tissue Regeneration

    No full text
    Background: Brain organoids are self-organized from human pluripotent stem cells and developed into various brain region following the developmental process of brain. Brain organoids provide promising approach for studying brain development process and neurological diseases and for tissue regeneration. Methods: In this review, we summarized the development of brain organoids technology, potential applications focusing on disease modeling for regeneration medicine, and multidisciplinary approaches to overcome current limitations of the technology. Results: Generations of brain organoids are categorized into two major classes by depending on the patterning method. In order to guide the differentiation into specific brain region, the extrinsic factors such as growth factors, small molecules, and biomaterials are actively studied. For better modelling of diseases with brain organoids and clinical application for tissue regeneration, improvement of the brain organoid maturation is one of the most important steps. Conclusion: Brain organoids have potential to develop into an innovative platform for pharmacological studies and tissue engineering. However, they are not identical replicas of their in vivo counterpart and there are still a lot of limitations to move forward to clinical applications
    corecore