Friday, May 9, 2025
5/9/2025
Neural Mechanisms of Performance Evaluation During Motor Sequence Learning - PROJECT SUMMARY Double faulting on match point is intensely disappointing. Yet it is also a performance error that could help improve your future serve. ‘Limbic’ structures such as the lateral habenula (LHb), ventral pallidum (VP) and ventral tegmental area (VTA) have classically been associated with hedonic functions. But this emphasis might result from behaviorist traditions that train lab animals with rewards and punishments. A more general function of the limbic system may be to impose valence on any prediction error, including mistakes that occur during motor performance. If this is the case, then decades of progress on how the brain processes reward can generalize to motor sequence tasks such as speech, sport, and musical performance. In past work, we discovered that when a male songbird unexpectedly sings the right note, its VTA dopamine (DA) neurons are activated in the same way as when a thirsty primate unexpectedly receives juice. And following song errors, its DA neurons are suppressed as when a primate experiences disappointing reward omission. We also found that when males sing to females, these performance evaluation signals are turned off and DA neurons are instead activated by female calls. These discoveries have important implications for motor learning circuits that motivate the proposed work. Frist, to determine how performance quality is evaluated in circuits upstream of VTA, we will anatomically identify inputs to VTA, perform lesions to test which are necessary for song learning, record VTA responses to microstimulation of distinct inputs, and conduct neural recordings to identify auditory error and/or timing signals important for error computation (Aim 1). Second, in past work we identified the VP as a hub for auditory, motor, and error processing during singing. In pilot experiments we are identifying LHb and subthalamic nucleus (STN) as novel targets of VP that also project to VTA. To dissect VP’s role in performance evaluation, we will anatomically define VP inputs and outputs, and will record STN-, LHb-, and motor cortex-projecting VP neurons during singing (Aim 2). Finally, our past discovery that DA error signals are turned off when males sing to females is unprecedented. To determine if DA signal gating is behaviorally relevant, we first test if males can learn from experimentally controlled errors with females present (Aim 3.1). To test if error signals are gated off globally, we will record neurons in VTA-projecting areas (auditory cortex, VP, STN, LHb) as we control both perceived error and female presence (Aim 3.2). Altogether, these studies will identify the neural correlates of the internal evaluation systems that construct motor sequences. A major impediment to understanding pathological activity patterns observed in BG-related diseases is a limited understanding of signal propagation through the healthy circuit. The proposed work aims to understand the functions of DA-BG signals and how they are processed at successive stages of the circuit. At stake in this issue is the potential to tailor therapies, such as neural circuit re-programming and deep brain stimulation for movement disorders, based on detailed knowledge of normal brain physiology.
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