Neural activity ramps in frontal cortex signal extended motivation during learning.

Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward-associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection-specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC)-to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward-associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.

Achieving goals takes motivation. An individual may have to complete a task many times for a future reward. For example, an animal may have to forage repeatedly to find food, or a person may have to study to get a good grade on a test. How these complex behaviors are encoded in the brain's wiring is not fully understood. Patients with injuries to the frontal cortex of the brain display a lack of motivation to pursue goals. This discovery suggests the frontal cortex plays a vital role in motivation and goal-directed behavior. Animal studies show that part of their brain's frontal cortex, the anterior cingulate cortex (ACC), helps them stay motivated and put extra effort into achieving goals. Yet, scientists wonder how particular actions are associated with specific goals and suspect the orbital frontal cortex (OFC) contains the blueprint to support this association. Regalado et al. show that the OFC and ACC work together during goal-seeking behavior in mice. In the experiments, mice learned to complete a task to achieve a sugar water reward. As the mice were learning, Regalado et al. recorded activity in the ACC and found that the ACC is active during goal-seeking behavior. They also discovered that the activity of neurons in the OFC increased the longer mice went without receiving a reward, up until the reward was achieved, signaling a motivational state. Animals not motivated enough to maximize their rewards did not have an increased OFC activity. The experiments also showed that the motivational signals in the OFC were conveyed to ACC to support goal-directed learning, especially linking actions to positive future outcomes. The experiments help explain how an increase in neuronal activity in the OFC helps to increase motivation and goal-seeking behavior supported by the ACC. More studies will help scientists learn more about these processes and develop drugs or other therapies that can help people who have learning difficulties or struggle with motivation because of an injury or mental illness.

Thalamus drives vocal onsets in the zebra finch courtship song.

While motor cortical circuits contain information related to specific movement parameters1, long-range inputs also have a critical role in action execution2,3. Thalamic projections can shape premotor activity2-6 and have been suggested7 to mediate the selection of short, stereotyped actions comprising more complex behaviours8. However, the mechanisms by which thalamus interacts with motor cortical circuits to execute such movement sequences remain unknown. Here we find that thalamic drive engages a specific subpopulation of premotor neurons within the zebra finch song nucleus HVC (proper name) and that these inputs are critical for the progression between vocal motor elements (that is, 'syllables'). In vivo two-photon imaging of thalamic axons in HVC showed robust song-related activity, and online perturbations of thalamic function caused song to be truncated at syllable boundaries. We used thalamic stimulation to identify a sparse set of thalamically driven neurons within HVC, representing ~15% of the premotor neurons within that network. Unexpectedly, this population of putative thalamorecipient neurons is robustly active immediately preceding syllable onset, leading to the possibility that thalamic input can initiate individual song components through selectively targeting these 'starter cells'. Our findings highlight the motor thalamus as a director of cortical dynamics in the context of an ethologically relevant behavioural sequence.