Spontaneous behaviour is structured by reinforcement without explicit reward

Markowitz, Jeffrey E.; Gillis, Winthrop F.; Jay, Maya; Wood, Jeffrey J.; Harris, Ryley W.; Cieszkowski, Robert; Scott, Rebecca; Brann, David H.; Koveal, Dorothy; Kula, Tomasz; Weinreb, Caleb; Osman, Mohammed Abdal Monium; Pinto, Sandra Romero; Uchida, Naoshige; Linderman, Scott W.; Sabatini, Bernardo L.; Datta, Sandeep Robert

doi:10.1038/s41586-022-05611-2

Cited by 123 publications

(91 citation statements)

References 88 publications

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“…In agreement with this, a recent study showed that spontaneous open-field behavior (without explicit reward) can be clustered into discrete sub-second behavioral modules (“syllables”), and that behavioral modules with bigger striatal dopamine transients are more likely to reoccur in the future. Furthermore, pairing optogenetic stimulation of dopaminergic neurons with specific behavioral modules reinforces subsequent use of those specific modules—an effect that was detectable even during a subsequent, nonstimulated session ( 46 ). Our present results complement this study by also showing the converse: Pairing-reduced dopaminergic signaling with a specific task—akin to eliciting a specific behavioral module—reduces future performance of the same specific task.…”

Section: Discussionmentioning

confidence: 99%

Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment

Cheung

Ding

Zhuang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Dopamine (DA) loss in Parkinson’s disease (PD) causes debilitating motor deficits. However, dopamine is also widely linked to reward prediction and learning, and the contribution of dopamine-dependent learning to movements that are impaired in PD—which often do not lead to explicit rewards—is unclear. Here, we used two distinct motor tasks to dissociate dopamine’s acute motoric effects vs. its long-lasting, learning-mediated effects. In dopamine-depleted mice, motor task performance gradually worsened with task exposure. Task experience was critical, as mice that remained in the home cage during the same period were relatively unimpaired when subsequently probed on the task. Repeated dopamine replacement treatments acutely rescued deficits and gradually induced long-term rescue that persisted despite treatment withdrawal. Surprisingly, both long-term rescue and parkinsonian performance decline were task specific, implicating dopamine-dependent learning. D1R activation potently induced acute rescue that gradually consolidated into long-term rescue. Conversely, reduced D2R activation potently induced parkinsonian decline. In dopamine-depleted mice, either D1R activation or D2R activation prevented parkinsonian decline, and both restored balanced activation of direct vs. indirect striatal pathways. These findings suggest that reinforcement and maintenance of movements—even movements not leading to explicit rewards—are fundamental functions of dopamine and provide potential mechanisms for the hitherto unexplained “long-duration response” by dopaminergic therapies in PD.

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Section: Discussionmentioning

confidence: 99%

Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment

Cheung

Ding

Zhuang

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…We have recently used depth MoSeq to show that the levels of the neuromodulator dopamine fluctuate within the dorsolateral striatum (DLS) during spontaneous behavior, and that these fluctuations are temporally aligned to syllable transitions 15 : On average, dopamine levels rise rapidly at the onset of each syllable, and then decline toward the end of the syllable. Furthermore, the average magnitude of dopamine fluctuations varies across syllables.…”

Section: Resultsmentioning

confidence: 99%

Keypoint-MoSeq: parsing behavior by linking point tracking to pose dynamics

Weinreb

Osman

Zhang

et al. 2023

Preprint

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Keypoint tracking algorithms have revolutionized the analysis of animal behavior, enabling investigators to flexibly quantify behavioral dynamics from conventional video recordings obtained in a wide variety of settings. However, it remains unclear how to parse continuous keypoint data into the modules out of which behavior is organized. This challenge is particularly acute because keypoint data is susceptible to high frequency jitter that clustering algorithms can mistake for transitions between behavioral modules. Here we present keypoint-MoSeq, a machine learning-based platform for identifying behavioral modules ("syllables") from keypoint data without human supervision. Keypoint-MoSeq uses a generative model to distinguish keypoint noise from behavior, enabling it to effectively identify syllables whose boundaries correspond to natural sub-second discontinuities inherent to mouse behavior. Keypoint-MoSeq outperforms commonly-used alternative clustering methods at identifying these transitions, at capturing correlations between neural activity and behavior, and at classifying either solitary or social behaviors in accordance with human annotations. Keypoint-MoSeq therefore renders behavioral syllables and grammar accessible to the many researchers who use standard video to capture animal behavior.

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“…28,29 The validity of the rapid signals has already been substantiated through comparisons to FSCV 9 and enables extensive studies of behaviorally related, fast neurochemical changes. 26,30 A thorough validation and comparison to established methods designed to monitor neurotransmission over longer periods must also be performed.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Recently, a new methodological paradigm has been opened by genetically encoded biosensors in combination with optical imaging technologies. When combined, these have potential to capture rapid dynamics over extended periods of time and an expanding palette of tools and techniques now allow for advances, such as multichannel recordings and depth resolution. , The validity of the rapid signals has already been substantiated through comparisons to FSCV and enables extensive studies of behaviorally related, fast neurochemical changes. , A thorough validation and comparison to established methods designed to monitor neurotransmission over longer periods must also be performed.…”

Section: Discussionmentioning

confidence: 99%

Within-Mice Comparison of Microdialysis and Fiber Photometry-Recorded Dopamine Biosensor during Amphetamine Response

Ejdrup

Wellbourne-Wood

Dreyer

et al. 2023

ACS Chem. Neurosci.

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A fundamental concept in neuroscience is the transmission of information between neurons via neurotransmitters, -modulators, and -peptides. For the past decades, the gold standard for measuring neurochemicals in awake animals has been microdialysis (MD). The emergence of genetically encoded fluorescence-based biosensors, as well as in vivo optical techniques such as fiber photometry (FP), has introduced technologically distinct means of measuring neurotransmission. To directly compare MD and FP, we performed concurrent within-animal recordings of extracellular dopamine (DA) in the dorsal striatum (DS) before and after administration of amphetamine in awake, freely behaving mice expressing the dopamine sensor dLight1.3b. We show that despite temporal differences, MD- and FP-based readouts of DA correlate well within mice. Down-sampling of FP data showed temporal correlation to MD data, with less variance observed using FP. We also present evidence that DA fluctuations periodically reach low levels, and naïve animals have rapid, predrug DA dynamics measured with FP that correlate to the subsequent pharmacodynamics of amphetamine as measured with MD and FP.

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Spontaneous behaviour is structured by reinforcement without explicit reward

Cited by 123 publications

References 88 publications

Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment

Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment

Keypoint-MoSeq: parsing behavior by linking point tracking to pose dynamics

Within-Mice Comparison of Microdialysis and Fiber Photometry-Recorded Dopamine Biosensor during Amphetamine Response

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