Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Basal Ganglia Circuit for Evaluating Action Outcomes


Nature  539, 289–293 (10 November 2016)

A basal ganglia circuit for evaluating action outcomes

Marcus Stephenson-Jones,

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

Medical Scientist Training Program & Program in Neuroscience, Stony Brook University, Stony Brook, New York 11790, USA

Department of Psychology, University of California Berkeley, Berkeley, California 94720, USA

Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California 94720, USA


The basal ganglia, a group of subcortical nuclei, play a crucial role in decision-making by selecting actions and evaluating their outcomes. While much is known about the function of the basal ganglia circuitry in selection, how these nuclei contribute to outcome evaluation is less clear. Here we show that neurons in the habenula-projecting globus pallidus (GPh) in mice are essential for evaluating action outcomes and are regulated by a specific set of inputs from the basal ganglia. We find in a classical conditioning task that individual mouse GPh neurons bidirectionally encode whether an outcome is better or worse than expected. Mimicking these evaluation signals with optogenetic inhibition or excitation is sufficient to reinforce or discourage actions in a decision-making task. Moreover, cell-type-specific synaptic manipulations reveal that the inhibitory and excitatory inputs to the GPh are necessary for mice to appropriately evaluate positive and negative feedback, respectively. Finally, using rabies-virus-assisted monosynaptic tracing, we show that the GPh is embedded in a basal ganglia circuit wherein it receives inhibitory input from both striosomal and matrix compartments of the striatum, and excitatory input from the ‘limbic’ regions of the subthalamic nucleus. Our results provide evidence that information about the selection and evaluation of actions is channelled through distinct sets of basal ganglia circuits, with the GPh representing a key locus in which information of opposing valence is integrated to determine whether action outcomes are better or worse than expected.

The GPh, a phylogenetically conserved non-motor output of the basal ganglia, excites the lateral habenula (LHb) that, in turn, drives inhibition onto dopamine neurons when an outcome is worse than expected. GPh neurons may thus play a key role in evaluating action outcomes by providing a source of ‘prediction error’ (PE) to the reward system, to drive reinforcement learning. In order to test this hypothesis, we first verified that we could selectively target GPh neurons in the entopeduncular nucleus (EP), the rodent homologue of the primate globus pallidus interna (GPi) where GPh neurons are located, on the basis of their expression of vesicular glutamate transporter 2 (Vglut2) and the neuropeptide somatostatin (Som), and that GPh neurons project exclusively to the LHb

Our results demonstrate that the GPh is a key locus where information of opposing valence is integrated, from a subset of basal ganglia circuits, to determine if an action is better or worse than expected. The outcome evaluation function of the GPh is probably mediated through bidirectional control of dopamine neurons, in which PE coding is critical for reinforcement learning. The GPh is well placed to bidirectionally influence dopaminergic activity as it provides tonic excitatory input to the LHb, which in turn regulates dopamine neurons disynaptically via the GABAergic rostromedial tegmental nucleus. Indeed, bidirectional changes in LHb firing have opposing effects on dopamine cell firing, and lesions of the LHb disrupt negative- and impair positive-reward PE coding in dopaminergic neurons.

We propose that an increase in GPh activity when an outcome is worse than expected    increases the excitatory drive    onto the LHb    to inhibit dopamine neurons and discourage actions,    whereas decreases in GPh activity    when an outcome is better than expected    remove the tonic excitation of the LHb    to increase dopaminergic activity and reinforce actions.

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