The design of modern scientific experiments requires the control and monitoring of many different data streams. However, the serial execution of programming instructions in a computer makes it a challenge to develop software that can deal with the asynchronous, parallel nature of scientific data. Here we present Bonsai, a modular, high-performance, open-source visual programming framework for the acquisition and online processing of data streams. We describe Bonsai's core principles and architecture and demonstrate how it allows for the rapid and flexible prototyping of integrated experimental designs in neuroscience. We specifically highlight some applications that require the combination of many different hardware and software components, including video tracking of behavior, electrophysiology and closed-loop control of stimulation.

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine–serotonin opponency with potential clinical implications.DOI: http://dx.doi.org/10.7554/eLife.20552.001

The basal ganglia, and the striatum in particular, have been implicated in the generation of contraversive movements. The striatum projects to downstream basal ganglia nuclei through two main circuits, originating in striatonigral and striatopallidal neurons, and different models postulate that the two pathways can work in opposition or synergistically. Here we show striatonigral and striatopallidal neurons are concurrently active during spontaneous contraversive movements. Furthermore, we show that unilateral optogenetic inhibition of either or both projection pathways disrupts contraversive movements. Consistently, simultaneous activation of both neuron types produces contraversive movements. Still, we also show that imbalanced activity between the pathways can result in opposing movements being driven by each projection pathway. These data show that balanced activity in both striatal projection pathways is critical for the generation of contraversive movements and highlights that imbalanced activity between the two projection pathways can result in opposing motor output.

It has been proposed that the activity of dopamine neurons approximates temporal difference (TD) prediction error, a teaching signal developed in reinforcement learning, a field of machine learning. However, whether this similarity holds true during learning remains elusive. In particular, some TD learning models predict that the error signal gradually shifts backward in time from reward delivery to a reward-predictive cue, but previous experiments failed to observe such a gradual shift in dopamine activity. Here we demonstrate conditions in which such a shift can be detected experimentally. These shared dynamics of TD error and dopamine activity narrow the gap between machine learning theory and biological brains, tightening a long-sought link..

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.