Sympathetic involvement in time-constrained sequential foraging

Appraising sequential offers relative to an unknown future opportunity and a time cost requires an optimization policy that draws on a learned estimate of an environment’s richness. Converging evidence points to a learning asymmetry, whereby estimates of this richness update with a bias toward integrating positive information. We replicate this bias in a sequential foraging (prey selection) task and probe associated activation within the sympathetic branch of the autonomic system, using trial-by-trial measures of simultaneously recorded cardiac autonomic physiology. We reveal a unique adaptive role for the sympathetic branch in learning. It was specifically associated with adaptation to a deteriorating environment: it correlated with both the rate of negative information integration in belief estimates and downward changes in moment-to-moment environmental richness, and was predictive of optimal performance on the task. The findings are consistent with a framework whereby autonomic function supports the learning demands of prey selection

Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making

Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, “rational” decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict.National Institute of Mental Health (Grant R01 MH060379)CHDI Foundation (Award A-5552)Army Research Office (Contract W911NF-10-1-0059

Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain

[Background] Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells.[Results] In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging.[Conclusions+ These findings support the use of commercial MNPs to track cells for short- and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.This work was supported by grants from (to AM-S): Spanish Ministry of Economy and Competitiveness (SAF2010-17167), Comunidad Autónoma Madrid (S2011-BMD-2336), Instituto Salud Carlos III (RETICS TerCel, RD12/0019/ 0013). This work was also supported by an institutional grant from Fundación Ramón Areces to the Center of Molecular Biology Severo Ochoa. The authors gratefully acknowledge the financial support of the Reina Sofia Foundation and Comunidad Autónoma Madrid (S2010-BMD-2460) to MR-G.Peer Reviewe