Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to noise in the brain's decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability. We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior.
- Tobias H Donner
- Tobias H Donner
- Tobias H Donner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: All subjects gave written informed consent, and consent to publish. The ethics committee of the Psychology Department of the University of Amsterdam approved the experiments (Id's: 2014-BC-3406; 2015-BC-4613; 2016-BC-6842).
- Klaas Enno Stephan, University of Zurich and ETH Zurich, Switzerland
© 2017, de Gee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Chemical neurotransmission constitutes one of the fundamental modalities of communication between neurons. Monitoring release of these chemicals has traditionally been difficult to carry out at spatial and temporal scales relevant to neuron function. To understand chemical neurotransmission more fully, we need to improve the spatial and temporal resolutions of measurements for neurotransmitter release. To address this, we engineered a chemi-sensitive, two-dimensional composite nanofilm that facilitates visualization of the release and diffusion of the neurochemical dopamine with synaptic resolution, quantal sensitivity, and simultaneously from hundreds of release sites. Using this technology, we were able to monitor the spatiotemporal dynamics of dopamine release in dendritic processes, a poorly understood phenomenon. We found that dopamine release is broadcast from a subset of dendritic processes as hotspots that have a mean spatial spread of 3.2 µm (full width at half maximum) and are observed with a mean spatial frequency of 1 hotspot per 7.5 µm of dendritic length. Major dendrites of dopamine neurons and fine dendritic processes, as well as dendritic arbors and dendrites with no apparent varicose morphology participated in dopamine release. Remarkably, these release hotspots colocalized with Bassoon, suggesting that Bassoon may contribute to organizing active zones in dendrites, similar to its role in axon terminals.
Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson's Disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free GCaMP fiber photometry to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of movement-related STN activity, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.