A basal ganglia circuit for evaluating action outcomes

Abstract

The basal ganglia, a group of subcortical nuclei, play a crucial role in decision making by selecting actions and evaluating their outcomes1,2. While much is known about the function of the basal ganglia circuitry in selection1,3,4, how these nuclei contribute to outcome evaluation is less clear. Here we show that neurons in the habenula-projecting globus pallidus (GPh) are essential for evaluating action outcomes and are regulated by a specific set of inputs from the basal ganglia. We found 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 revealed 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 tracing5, we discovered 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 (STN). Our results provide the first direct 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 where information of opposing valence is integrated to determine whether action outcomes are better or worse than expected.

The Lateral Habenula Circuitry: Reward Processing and Cognitive Control

“…In particular, the LHb has received substantial research attention because of its involvement in processing of reward and aversive information, cognitive flexibility, and emotion Zhao et al, 2015). Dysfunctions of the LHb have been implicated in mental illnesses associated with maladaptive processing of positive and negative valence stimuli (Proulx et al, 2014); thus, it is important to understand molecular, cellular, and circuit interactions of the LHb circuits that may contribute to these disorders.…”

“…In addition to VTA afferents, the LHb receives major glutamatergic and GABAergic inputs from the globus pallidus interna (GPi), lateral hypothalamus (LH), basal forebrain, and ventral pallidum Shabel et al, 2012;Golden et al, 2016;Stamatakis et al, 2016). Neurons in the GPi and LH corelease glutamate and GABA as their neurotransmitters with the net effect that they can increase LHb firing when activated (Shabel et al, 2012(Shabel et al, , 2014Stamatakis et al, 2016).…”

“…Neurons in the GPi and LH corelease glutamate and GABA as their neurotransmitters with the net effect that they can increase LHb firing when activated (Shabel et al, 2012(Shabel et al, , 2014Stamatakis et al, 2016). In both cases, neurons in the LH and GPi are modulated by the cues that predict the availability of reward and aversion Bromberg-Martin et al, 2010) and can drive aversive behavior (Shabel et al, 2012;Stamatakis et al, 2016). Recent experiments have shown that shifted corelease of glutamate and GABA is a crucial mediator of aversive states, such as depression and cocaine withdrawal (Shabel et al, 2014;Meye et al, 2016).…”

“…In both cases, neurons in the LH and GPi are modulated by the cues that predict the availability of reward and aversion Bromberg-Martin et al, 2010) and can drive aversive behavior (Shabel et al, 2012;Stamatakis et al, 2016). Recent experiments have shown that shifted corelease of glutamate and GABA is a crucial mediator of aversive states, such as depression and cocaine withdrawal (Shabel et al, 2014;Meye et al, 2016).…”

“…Such behavioral choice is subserved by the brain reward circuitry encompassing the basal ganglia and the mesocorticolimbic dopamine system (Floresco et al, 2008;Graybiel, 2008). The LHb has recently emerged as a key nucleus in this circuitry (Lecourtier and Kelly, 2007;Proulx et al, 2014) as neurons in this nucleus are excited by the expectation of unpleasant events or when an outcome is worse than expected, and are inhibited by the expectation of reward or when an outcome is better than expected Hikosaka, 2007, 2009;Hong et al, 2011;Lawson et al, 2014). In other words, LHb neurons encode motivational values and PEs (Hikosaka, 2010;Proulx et al, 2014), in an opposite manner compared with dopamine neurons in the VTA and SNc (Schultz, 1998).…”