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AbstractLearning about positive and negative outcomes of actions is crucial for survival and underpinned by conserved circuits including the striatum. How associations between actions and outcomes are formed is not fully understood, particularly when the outcomes have mixed positive and negative features. We developed a novel foraging (‘bandit’) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca++ imaging, we monitored activity of visually identified anterodorsal striatal striosomal and matrix neurons. We found that action-outcome associations for reward and punishment were encoded in parallel in partially overlapping populations. Single neurons could, for one action, encode outcomes of opposing valence. Striosome compartments consistently exhibited stronger representations of reinforcement outcomes than matrix, especially for high reward or punishment prediction errors. These findings demonstrate multiplexing of action-outcome contingencies by single identified striatal neurons and suggest that striosomal neurons are particularly important in action-outcome learning.

© 2020, The Author(s). Sensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Modulation by the prefrontal cortex (PFC) is thought to be key for both processes, but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC). Using a visually guided two-choice behavioral paradigm with multiple cue-response mappings, we dissociated the sensory and motor response components of sensorimotor control. Projection-specific two-photon calcium imaging and optogenetic manipulations show that ACC outputs to the superior colliculus, a key midbrain structure for response selection, principally coordinate specific motor responses. Importantly, ACC outputs exert control by reducing the innate response bias of the superior colliculus. In contrast, ACC outputs to the visual cortex facilitate sensory processing of visual cues. Our results ascribe motor and sensory roles to ACC projections to the superior colliculus and the visual cortex and demonstrate for the first time a circuit motif for PFC function wherein anatomically non-overlapping output pathways coordinate complementary but distinct aspects of visual sensorimotor behavior.

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd Ray Guillery made major contributions to our understanding of the development and function of the brain. One of his principal conceptual insights, developed together with Murray Sherman [S.M. Sherman & R.W. Guillery (2001) Exploring the Thalamus. Elsevier, Amstrerdam; S. Sherman & R. Guillery (2006) Exploring the Thalamus and Its Role in Cortical Functioning. Academic Press, New York, NY; S.M. Sherman & R.W. Guillery (2013) Functional Connections of Cortical Areas: A New View from the Thalamus. MIT Press, Cambridge, MA and then in his last book (R. Guillery (2017) The Brain as a Tool: A Neuroscientist's Account. Oxford University Press, Oxford, UK)], was that the brain is a ‘tool’ to understand the world. In this view, the brain does not passively process sensory information and use the result to inform motor outputs. Rather, sensory and motor signals are widely broadcast and inextricably linked, with ongoing sensorimotor transformations serving as the basis for interaction with the outside world. Here, we describe recent studies from our laboratory and others which demonstrate this astute framing of the link among sensation, perception, and action postulated by Guillery and others [G. Deco & E.T. Rolls (2005) Prog Neurobiol, 76, 236–256; P. Cisek & J.F. Kalaska (2010) Annu Rev Neurosci, 33, 269-298]. Guillery situated his understanding in the deeply intertwined relationship between the thalamus and cortex, and importantly in the feedback from cortex to thalamus which in turn influences feed-forward drive to cortex [S.M. Sherman & R.W. Guillery (2001) Exploring the Thalamus. Elsevier, Amstrerdam; S. Sherman & R. Guillery (2006) Exploring the Thalamus and Its Role in Cortical Functioning. Academic Press, New York, NY]. We extend these observations to argue that brain mechanisms for sensorimotor transformations involve cortical and subcortical circuits that create internal models as a subst

Striosomes were discovered several decades ago as neurochemically identified zones in the striatum, yet technical hurdles have hampered the study of the functions of these striatal compartments. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1- CreER;Ai14 mice to image simultaneously the activity of striosomal and matrix neurons as mice performed an auditory conditioning task. With this method, we identified circumscribed zones of tdTomato-labeled neuropil that correspond to striosomes as verified immunohistochemically. Neurons in both striosomes and matrix responded to reward-predicting cues and were active during or after consummatory licking. However, we found quantitative differences in response strength: striosomal neurons fired more to reward-predicting cues and encoded more information about expected outcome as mice learned the task, whereas matrix neurons were more strongly modulated by recent reward history. These findings open the possibility of harnessing in vivo imaging to determine the contributions of striosomes and matrix to striatal circuit function., National Institute of Neurological Diseases and Stroke (U.S.) (Grant U01 NS090473), National Eye Institute (Grant R01 EY007023), National Science Foundation (U.S.) (Grant EF1451125), National Eye Institute (Grant F32 EY024857), National Institute of Mental Health (U.S.) (Grant K99 MH112855)