Error-related signaling in nucleus accumbens D2 receptor-expressing neurons guides inhibition-based choice behavior in mice.

Learned associations between environmental cues and the outcomes they predict (cue-outcome associations) play a major role in behavioral control, guiding not only which responses we should perform, but also which we should inhibit, in order to achieve a specific goal. The encoding of such cue-outcome associations, as well as the performance of cue-guided choice behavior, is thought to involve dopamine D1 and D2 receptor-expressing medium spiny neurons (D1-/D2-MSNs) of the nucleus accumbens (NAc). Here, using a visual discrimination task in male mice, we assessed the role of NAc D1-/D2-MSNs in cue-guided inhibition of inappropriate responding. Cell-type specific neuronal silencing and in-vivo imaging revealed NAc D2-MSNs to contribute to inhibiting behavioral responses, with activation of NAc D2-MSNs following response errors playing an important role in optimizing future choice behavior. Our findings indicate that error-signaling by NAc D2-MSNs contributes to the ability to use environmental cues to inhibit inappropriate behavior.

Frontal-Sensory Cortical Projections Become Dispensable for Attentional Performance Upon a Reduction of Task Demand in Mice.

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of these projecting neurons is dependent on the extent of task demand. Here, we first examined how behavior outcomes depend on the number of locations for mice to pay attention and touch for successful performance, and found that the 2-choice serial reaction time task (2CSRTT) is less task demanding than the 5CSRTT. We then employed optogenetics to demonstrate that suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. These results suggest that ACAVIS projections are necessary when task demand is high, but once a task demand is lowered, ACAVIS neuron activity becomes dispensable to adjust attentional performance. These findings support a model that the frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.

Chemogenetic Suppression of the Subthalamic Nucleus Induces Attentional Deficits and Impulsive Action in a Five-Choice Serial Reaction Time Task in Mice.

The subthalamic nucleus (STN), a key component of the basal ganglia circuitry, receives inputs from broad cerebral cortical areas and relays cortical activity to subcortical structures. Recent human and animal studies have suggested that executive function, which is assumed to consist of a set of different cognitive processes for controlling behavior, depends on precise information processing between the cerebral cortex and subcortical structures, leading to the idea that the STN contains neurons that transmit the information required for cognitive processing through their activity, and is involved in such cognitive control directly and dynamically. On the other hand, the STN activity also affects intracellular signal transduction and gene expression profiles influencing plasticity in other basal ganglia components. The STN may also indirectly contribute to information processing for cognitive control in other brain areas by regulating slower signaling mechanisms. However, the precise correspondence and causal relationship between the STN activity and cognitive processes are not fully understood. To address how the STN activity is involved in cognitive processes for controlling behavior, we applied Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic manipulation of neural activity to behavioral analysis using a touchscreen operant platform. We subjected mice selectively expressing DREADD receptors in the STN neurons to a five-choice serial reaction time task, which has been developed to quantitatively measure executive function. Chemogenetic suppression of the STN activity reversibly impaired attention, especially required under highly demanding conditions, and increased impulsivity but not compulsivity. These findings, taken together with the results of previous lesion studies, suggest that the STN activity, directly and indirectly, participates in cognitive processing for controlling behavior, and dynamically regulates specific types of subprocesses in cognitive control probably through fast synaptic transmission.