All Publications


  • Striosomes Mediate Value-Based Learning Vulnerable in Age and a Huntington's Disease Model. Cell Friedman, A. n., Hueske, E. n., Drammis, S. M., Toro Arana, S. E., Nelson, E. D., Carter, C. W., Delcasso, S. n., Rodriguez, R. X., Lutwak, H. n., DiMarco, K. S., Zhang, Q. n., Rakocevic, L. I., Hu, D. n., Xiong, J. K., Zhao, J. n., Gibb, L. G., Yoshida, T. n., Siciliano, C. A., Diefenbach, T. J., Ramakrishnan, C. n., Deisseroth, K. n., Graybiel, A. M. 2020

    Abstract

    Learning valence-based responses to favorable and unfavorable options requires judgments of the relative value of the options, a process necessary for species survival. We found, using engineered mice, that circuit connectivity and function of the striosome compartment of the striatum are critical for this type of learning. Calcium imaging during valence-based learning exhibited a selective correlation between learning and striosomal but not matrix signals. This striosomal activity encoded discrimination learning and was correlated with task engagement, which, in turn, could be regulated by chemogenetic excitation and inhibition. Striosomal function during discrimination learning was disturbed with aging and severely so in a mouse model of Huntington's disease. Anatomical and functional connectivity of parvalbumin-positive, putative fast-spiking interneurons (FSIs) to striatal projection neurons was enhanced in striosomes compared with matrix in mice that learned. Computational modeling of these findings suggests that FSIs can modulate the striosomal signal-to-noise ratio, crucial for discrimination and learning.

    View details for DOI 10.1016/j.cell.2020.09.060

    View details for PubMedID 33113354

  • Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making CELL Friedman, A., Homma, D., Bloem, B., Gibb, L. G., Amemori, K., Hu, D., Delcasso, S., Truong, T. F., Yang, J., Hood, A. S., Mikofalvy, K. A., Beck, D. W., Nguyen, N., Nelson, E. D., Arana, S., Bruegge, R., Goosens, K. A., Graybiel, A. M. 2017; 171 (5): 1191-+

    Abstract

    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. VIDEO ABSTRACT.

    View details for DOI 10.1016/j.cell.2017.10.017

    View details for Web of Science ID 000415317000020

    View details for PubMedID 29149606

    View details for PubMedCentralID PMC5734095

  • Analysis of complex neural circuits with nonlinear multidimensional hidden state models PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Friedman, A., Slocum, J. F., Tyulmankov, D., Gibb, L. G., Altshuler, A., Ruangwises, S., Shi, Q., Arana, S., Beck, D. W., Sholes, J. C., Graybiel, A. M. 2016; 113 (23): 6538–43

    Abstract

    A universal need in understanding complex networks is the identification of individual information channels and their mutual interactions under different conditions. In neuroscience, our premier example, networks made up of billions of nodes dynamically interact to bring about thought and action. Granger causality is a powerful tool for identifying linear interactions, but handling nonlinear interactions remains an unmet challenge. We present a nonlinear multidimensional hidden state (NMHS) approach that achieves interaction strength analysis and decoding of networks with nonlinear interactions by including latent state variables for each node in the network. We compare NMHS to Granger causality in analyzing neural circuit recordings and simulations, improvised music, and sociodemographic data. We conclude that NMHS significantly extends the scope of analyses of multidimensional, nonlinear networks, notably in coping with the complexity of the brain.

    View details for DOI 10.1073/pnas.1606280113

    View details for Web of Science ID 000377155400055

    View details for PubMedID 27222584

    View details for PubMedCentralID PMC4988606