Striatal dopamine D2 receptors regulate effort but not value-based decision making and alter the dopaminergic encoding of cost.

Deficits in goal-directed motivation represent a debilitating symptom for many patients with schizophrenia. Impairments in motivation can arise from deficits in processing information about effort and or value, disrupting effective cost-benefit decision making. We have previously shown that upregulated dopamine D2 receptor expression within the striatum (D2R-OE mice) decreases goal-directed motivation. Here, we determine the behavioral and neurochemical mechanisms behind this deficit. Female D2R-OE mice were tested in several behavioral paradigms including recently developed tasks that independently assess the impact of Value or Effort manipulations on cost-benefit decision making. In vivo microdialysis was used to measure extracellular dopamine in the striatum during behavior. In a value-based choice task, D2R-OE mice show normal sensitivity to changes in reward value and used reward value to guide their actions. In an effort-based choice task, D2R-OE mice evaluate the cost of increasing the number of responses greater relative to the effort cost of longer duration responses compared to controls. This shift away from choosing to repeatedly execute a response is accompanied by a dampening of extracellular dopamine in the striatum during goal-directed behavior. In the ventral striatum, extracellular dopamine level negatively correlates with response cost in controls, but this relationship is lost in D2R-OE mice. These results show that D2R signaling in the striatum, as observed in some patients with schizophrenia, alters the relationship between effort expenditure and extracellular dopamine. This dysregulation produces motivation deficits that are specific to effort but not value-based decision making, paralleling the effort-based motivational deficits observed in schizophrenia.

Mushroom body extrinsic neurons in the honeybee (Apis mellifera) brain integrate context and cue values upon attentional stimulus selection.

Multimodal GABA-immunoreactive feedback neurons in the honeybee brain connecting the output region of the mushroom body with its input are expected to tune the input to the mushroom body in an experience-dependent way. These neurons are known to change their rate responses to learned olfactory stimuli. In this work we ask whether these neurons also transmit learned attentional effects during multisensory integration. We find that a visual context and an olfactory cue change the rate responses of these neurons after learning according to the associated values of both context and cue. The learned visual context promotes attentional response selection by enhancing olfactory stimulus valuation at both the behavioral and the neural level. During a rewarded visual context, bees reacted faster and more reliably to a rewarded odor. We interpreted this as the result of the observed enhanced neural discharge toward the odor. An unrewarded context reduced already low rate responses to the unrewarded odor. In addition to stimulus valuation, these feedback neurons generate a neural error signal after an incorrect behavioral response. This might act as a learning signal in feedback neurons. All of these effects were exclusively found in trials in which the animal prepares for a motor response that happens during attentional stimulus selection. We discuss possible implications of the results for the feedback connections of the mushroom body.

Progressive cognitive dysfunction in spinocerebellar ataxia type 3.

BACKGROUND: Although it is well established that there is cognitive dysfunction in spinocerebellar ataxia type 3 (SCA3), it is unknown whether cognition deteriorates with disease progression. We therefore prospectively studied cognitive function in patients with SCA3. METHODS: Eleven patients with SCA3 were assessed using an extensive neuropsychological test battery and retested after 3.5 ± 0.4 years. RESULTS: In addition to ataxia and motor control, verbal learning and verbal and figural memory deteriorated significantly during the follow-up period. An increase in depressive symptoms was not observed. CONCLUSIONS: The observation that memory and learning abilities deteriorated with disease progression suggests that cognitive dysfunction is an integral part of SCA3. Because the applied tests for memory function did not require motor responses, cognitive decline cannot be attributed to progressive cerebellar ataxia. The deterioration of verbal and figural memory can be explained either by extracerebellar pathology or by disruption of cerebellar-cerebral circuitries.