Dopamine plays a key role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (i.e., reward prediction error, RPE)1-3, but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neurons based on responses to odours and outcomes: approximately half of the neurons (Type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with RPE coding. The other half of neurons showed persistent activity during the delay between odour and outcome, that was modulated positively (Type II, 31%) or negatively (Type III, 17%) by the value of outcomes. While the activity of Type I neurons was sensitive to actual outcomes (i.e., when the reward was delivered as expected vs. unexpectedly omitted), the activity of Types II and III neurons was determined predominantly by reward-predicting odours. We “tagged” dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 (ChR2) and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of Type I and all GABAergic neurons were of Type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate RPE.

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2.