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    Pictured above is Figure 2 from the article The neural basis of reversal learning: An updated perspective (A. Izquierdo, J.L. Brigman, A.K. Radke, P.H. Rudebeck, A. Holmes). 

    Established in 1976, Neuroscience is the flagship journal of IBRO and is overseen by the IBRO Publications CommitteeElsevier publishes 28 issues per year. 

    The journal features papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, is considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.

    READ the current issue of IBRO Neuroscience (vol. 345)  published on 14 March 2017, a Special Issue on Cognitive Flexibility: Development, Disease, and Treatment, edited by Elizabeth Powell and Michael Ragozzino.

    All organisms must adapt to dynamic environmental demands for survival, and the ability to switch thought and/or response patterns characterizes cognitive flexibility. Cognitive flexibility generates novel solutions to particular problems or challenges. Over the past two decades there have been significant advances in understanding the neural basis of cognitive flexibility, and the accompanying neuropathophysiology underlying deficits in psychiatric and neurological disorders. This issue of Neuroscience brings into focus current findings and conceptualizations about the neuroscience of cognitive flexibility through a collection of research and review articles.

    Highlights from this issue include:

    The neural basis of reversal learning: An updated perspective

    (A. Izquierdo, J.L. Brigman, A.K. Radke, P.H. Rudebeck, A. Holmes)

    Reversal learning paradigms are among the most widely used tests of cognitive flexibility and have been used as assays, across species, for altered cognitive processes in a host of neuropsychiatric conditions. Based on recent studies in humans, non-human primates, and rodents, the notion that reversal learning tasks primarily measure response inhibition, has been revised. In this review, we describe how cognitive flexibility is measured by reversal learning and discuss new definitions of the construct validity of the task that are serving as a heuristic to guide future research in this field. We also provide an update on the available evidence implicating certain cortical and subcortical brain regions in the mediation of reversal learning, and an overview of the principal neurotransmitter systems involved.

    Orbitofrontal cortex reflects changes in response–outcome contingencies during probabilistic reversal learning

    (L.R. Amodeo, M.S. McMurray, J.D. Roitman)

    In a continuously changing environment, in which behavioral outcomes are rarely certain, animals must be able to learn to integrate feedback from their choices over time and adapt to changing reward contingencies to maintain flexible behavior. The orbitofrontal region of prefrontal cortex (OFC) has been widely implicated as playing a role in the ability to flexibly control behavior. We used a probabilistic reversal learning task to measure rats’ behavioral flexibility and its neural basis in the activity of single neurons in OFC. In this task, one lever, designated as ‘correct’, was rewarded at a high probability (80%) and a second, spatially distinct lever, designated as ‘incorrect’, was rewarded at a low probability (20%). Once rats reached a learning criterion for reliably selecting the correct lever, reward contingencies of the two levers were switched, and daily sessions were conducted until rats reliably selected the new correct lever. All rats performed the initial Acquisition and subsequent Reversal successfully, with more sessions needed to learn the Reversal. OFC neurons were recorded during five behavioral sessions spanning Acquisition and Reversal learning. The dominant pattern of neural responding in OFC, identified by principal component analysis of the population of neurons recorded, was modulated by reward outcome across behavioral sessions. Generally, activity was higher following rewarded choices than unrewarded. However, there was a correlation between reduced responses to reward following incorrect choices and the establishment of the preference for the correct lever. These results show how signaling by individual OFC neurons may participate in the flexible adaptation of behavior under changing reward contingencies.

    Evidence of a role for orbital prefrontal cortex in preventing over-generalization to moderate predictors of biologically significant events

    (J.E. Trow, N.S. Hong, A.M. Jones, J. Lapointe, J.K. MacPhail, R.J. McDonald)

    The mammalian brain is specialized to acquire information about environmental predictors of biologically significant events. However, environments contain an array of stimuli from which animals must ascertain which ones are meaningful in the current situation. This kind of uncertainty is inherent in the discriminative fear conditioning to context task (DFCTC) during which rats are trained to associate one context with foot-shock and another distinct context with no event. Although the contexts differ on several dimensions, they also share similarities making some cues perfect predictors, but others moderate predictors. Appropriate responding requires animals to determine which cues are relevant in the current situation and the ability to constrain their responses only to those perfect predictors. The orbital prefrontal cortex (OPFC) is thought to modulate this function as OPFC lesions result in over-generalization during DFCTC. Two experiments were conducted; the first was intended to dissociate the role of the OPFC in acquisition and expression of DFCTC, and the second intended to determine if the OPFC will also function to constrain responses during an appetitive version of DFCTC. We found that inactivation of the OPFC prior to assessment measures resulted in generalized responses on the appetitive and aversive task, however, these effects may be more prominent during the aversive task. Despite generalization during activity testing, rats were able to discriminate between the two contexts during preference. These results point to a broader role for the OPFC constraining responses to perfect predictors of biologically significant events in uncertain contexts.


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