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1. Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release

   https://doi.org/10.1038/s41598-021-99350-5  

   Nadel, J. A. ; Pawelko, S. S. ; Scott, J. R. ; McLaughlin, R. ; Fox, M. ; Ghanem, M. ; van der Merwe, R. ; Hollon, N. G. ; Ramsson, E. S. ; Howard, C. D. ( December 2021 , Scientific Reports)

   null (Ed.)

   Abstract Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling. 

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2. Adolescents exhibit reduced Pavlovian biases on instrumental learning

   https://doi.org/10.1038/s41598-020-72628-w  

   Raab, Hillary A. ; Hartley, Catherine A. ( September 2020 , Scientific Reports)

   Multiple learning systems allow individuals to flexibly respond to opportunities and challenges present in the environment. An evolutionarily conserved “Pavlovian” learning mechanism couples valence and action, promoting a tendency to approach cues associated with reward and to inhibit action in the face of anticipated punishment. Although this default response system may be adaptive, these hard-wired reactions can hinder the ability to learn flexible “instrumental” actions in pursuit of a goal. Such constraints on behavioral flexibility have been studied extensively in adults. However, the extent to which these valence-specific response tendencies bias instrumental learning across development remains poorly characterized. Here, we show that while Pavlovian response biases constrain flexible action learning in children and adults, these biases are attenuated in adolescents. This adolescent-specific reduction in Pavlovian bias may promote unbiased exploration of approach and avoidance responses, facilitating the discovery of rewarding behavior in the many novel contexts that adolescents encounter.

    

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3. Elements of a compound elicit little conditioned reinforcement

   https://doi.org/10.1037/xan0000296  

   Valeria V. González ; Benjamin M. Seitz ; Rachel Formaker ; and Aaron P. Blaisdell ( January 2022 , Journal of experimental psychology)

   The acquisition of instrumental responding can be supported by primary reinforcers or by conditional (also known as secondary) reinforcers that themselves have an association to a primary reinforcer. While primary reinforcement has been heavily studied for the past century, the associative basis of conditioned reinforcement has received comparatively little experimental examination. Yet conditioned reinforcement has been employed as an important behavioral assay in neuroscience studies, and thus an analysis of its associative basis is called for. We evaluated the extent to which an element from a previously trained compound would facilitate conditioned reinforcement. Three groups of rats received Pavlovian conditioning with a visual-auditory compound cue followed by food. After training, a lever was made available that, when pressed, produced the same trained compound (group compound), only the auditory cue (group element), or a novel auditory cue (group control). The rats in group compound pressed the lever at a higher rate than did rats in either group element or group control, demonstrating a strong conditioned reinforcement effect only in group compound. Interestingly, there was almost no difference in responding between group element and group control. The implications of this generalization decrement in conditioned reinforcement are discussed—particularly as they relate to research in behavioral neuroscience. 

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4. Elements of a Compound Elicit Little Conditioned Reinforcement

   González, V. V. ; Seitz, B. M. ; Formaker, R. ; Blaisdell, A. P. ( January 2021 , Journal of experimental psychology)

   null (Ed.)

   The acquisition of instrumental responding can be supported by primary reinforcers or by conditional (also known as secondary) reinforcers that themselves have an association to a primary reinforcer. While primary reinforcement has been heavily studied for the past century, the associative basis of conditioned reinforcement has received comparatively little experimental examination. Yet conditioned reinforcement has been employed as an important behavioral assay in neuroscience studies, and thus an analysis of its associative basis is called for. We evaluated the extent to which an element from a previously trained compound would facilitate conditioned reinforcement. Three groups of rats received Pavlovian conditioning with a visual-auditory compound cue followed by food. After training, a lever was made available that, when pressed, produced the same trained compound (group compound), only the auditory cue (group element), or a novel auditory cue (group control). The rats in group compound pressed the lever at a higher rate than did rats in either group element or group control, demonstrating a strong conditioned reinforcement effect only in group compound. Interestingly, there was almost no difference in responding between group element and group control. The implications of this generalization decrement in conditioned reinforcement are discussed—particularly as they relate to research in behavioral neuroscience. 

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5. Changes in Resting State Functional Connectivity Associated with Dynamic Adaptation of Wrist Movements

   https://doi.org/10.1523/JNEUROSCI.1916-22.2023  

   Farrens, Andria J. ; Vahdat, Shahabeddin ; Sergi, Fabrizio ( March 2023 , The Journal of Neuroscience)

   Dynamic adaptation is an error-driven process of adjusting planned motor actions to changes in task dynamics (Shadmehr, 2017). Adapted motor plans are consolidated into memories that contribute to better performance on re-exposure. Consolidation begins within 15 min following training (Criscimagna-Hemminger and Shadmehr, 2008), and can be measured via changes in resting state functional connectivity (rsFC). For dynamic adaptation, rsFC has not been quantified on this timescale, nor has its relationship to adaptative behavior been established. We used a functional magnetic resonance imaging (fMRI)-compatible robot, the MR-SoftWrist (Erwin et al., 2017), to quantify rsFC specific to dynamic adaptation of wrist movements and subsequent memory formation in a mixed-sex cohort of human participants. We acquired fMRI during a motor execution and a dynamic adaptation task to localize brain networks of interest, and quantified rsFC within these networks in three 10-min windows occurring immediately before and after each task. The next day, we assessed behavioral retention. We used a mixed model of rsFC measured in each time window to identify changes in rsFC with task performance, and linear regression to identify the relationship between rsFC and behavior. Following the dynamic adaptation task, rsFC increased within the cortico-cerebellar network and decreased interhemispherically within the cortical sensorimotor network. Increases within the cortico-cerebellar network were specific to dynamic adaptation, as they were associated with behavioral measures of adaptation and retention, indicating that this network has a functional role in consolidation. Instead, decreases in rsFC within the cortical sensorimotor network were associated with motor control processes independent from adaptation and retention.

   SIGNIFICANCE STATEMENTMotor memory consolidation processes have been studied via functional magnetic resonance imaging (fMRI) by analyzing changes in resting state functional connectivity (rsFC) occurring more than 30 min after adaptation. However, it is unknown whether consolidation processes are detectable immediately (<15 min) following dynamic adaptation. We used an fMRI-compatible wrist robot to localize brain regions involved in dynamic adaptation in the cortico-thalamic-cerebellar (CTC) and cortical sensorimotor networks and quantified changes in rsFC within each network immediately after adaptation. Different patterns of change in rsFC were observed compared with studies conducted at longer latencies. Increases in rsFC in the cortico-cerebellar network were specific to adaptation and retention, while interhemispheric decreases in the cortical sensorimotor network were associated with alternate motor control processes but not with memory formation.

    

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