The motor cortex is far from a stable conduit for motor commands and instead undergoes significant changes during learning. An understanding of motor cortex plasticity has been advanced greatly using rodents as experimental animals. Two major focuses of this research have been on the connectivity and activity of the motor cortex. The motor cortex exhibits structural changes in response to learning, and substantial evidence has implicated the local formation and maintenance of new synapses as crucial substrates of motor learning. This synaptic reorganization translates into changes in spiking activity, which appear to result in a modification and refinement of the relationship between motor cortical activity and movement. This review presents the progress that has been made using rodents to establish the motor cortex as an adaptive structure that supports motor learning.

Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood. Here, we examined the involvement of the IC in the expression of cue-triggered food approach in mice trained with a Pavlovian conditioning paradigm. We observed a significant change in neuronal firing during presentation of the cue. Pharmacological silencing of the IC inhibited food port approach. Such a behavior could be recapitulated by temporally selective inactivation during the cue. These findings represent the first evidence, to our knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral output, and demonstrate a causal link between cue responses and feeding behaviors.insular cortex | reward | anticipation | cue | learning I n natural environments, animals use sensory information from various sources to predict the availability of food (1-3). Repeated pairings of a neutral stimulus with the availability of food leads to the formation of associations. Upon association, foodpredicting cues become capable of triggering the expectation of food. These expectations drive motivation for food seeking and food consumption (4-6). It is generally believed that cues drive behavior by activating reward-related circuits responsible for coordinating food seeking and food consumption. A large body of evidence shows that regions like the amygdala, ventral striatum, orbitofrontal and prefrontal cortices, and ventral tegmental area can be activated by anticipatory cues (7-12). Although the reward circuitry involved in cue-triggered, food-related behaviors has been extensively studied, relatively little attention has been devoted to the role of sensory cortical areas in this process. The insular cortex (IC), for instance, has traditionally been studied for its role in the consummatory and postconsummatory phases of feeding (13)(14)(15)(16)(17). Neuronal ensembles in the IC are involved in taste processing and learning (18-21), and IC function is believed to be limited to the evaluative and sensory aspects of food consumption (22,23). More recent evidence, however, has suggested that the IC can also be involved in processing cues associated with food availability or delivery of addictive drugs (24-28). The presence of neurons that encode for both anticipatory cues and taste suggests a functional integration of reward and expectation processing. The prediction emerging from these studies is that manipulations of IC anticipatory activity might have an impact on food-directed and, in general, reward-directed behaviors. Although pharmacological manipul...

A substantial reorganization of neural activity and neuron-to-movement relationship in motor cortical circuits accompanies the emergence of reproducible movement patterns during motor learning. Little is known about how this tempest of neural activity restructuring impacts the stability of network states in recurrent cortical circuits. To investigate this issue, we reanalyzed data in which we recorded for 14 days via population calcium imaging the activity of the same neural populations of pyramidal neurons in layer 2/3 and layer 5 of forelimb motor and pre-motor cortex in mice during the daily learning of a lever-press task. We found that motor cortex network states remained stable with respect to the critical network state during the extensive reorganization of both neural population activity and its relation to lever movement throughout learning. Specifically, layer 2/3 cortical circuits unceasingly displayed robust evidence for operating at the critical network state, a regime that maximizes information capacity and transmission, and provides a balance between network robustness and flexibility. In contrast, layer 5 circuits operated away from the critical network state for all 14 days of recording and learning. In conclusion, this result indicates that the wide-ranging malleability of synapses, neurons, and neural connectivity during learning operates within the constraint of a stable and layer-specific network state regarding dynamic criticality, and suggests that different cortical layers operate under distinct constraints because of their specialized goals.

Dopamine is essential for the production of vigorous movements, but how dopamine modifies the gain of motor commands remains unclear. Here, we developed a dexterous motor task in which head-restrained mice self-initiate fast and large-amplitude lever pushes with their left forelimb to earn rewards. We show that this task is goal-directed and depends on cortico-striatal circuits in the hemisphere contralateral to the limb used to push the lever. We find that unilateral loss of midbrain dopamine neurons reduces the speed and amplitude of lever pushes, and that levodopa treatment rapidly restores motor vigor, consistent with parkinsonian bradykinesia. Photometry recordings of striatal dopamine levels indicate that the therapeutic efficacy of levodopa does not require phasic dopamine release. In dopamine-intact mice, optogenetic stimulation of midbrain dopamine neurons calibrated to mimic transients evoked by rewards is also insufficient to increase the speed and amplitude of forelimb movements. Together, our data show that phasic dopamine transients are unlikely to specify the vigor of forelimb movements online as they are being executed, and suggest instead that dopamine plays a permissive role in the selection and production of vigorous movements. Our findings have important implications for our understanding of how the basal ganglia contribute to motor control under physiological conditions and in Parkinson's disease.