The ability to shift between repetitive and goal-directed actions is a hallmark of cognitive control. Previous studies have reported that adaptive shifts in behavior are accompanied by changes of neural activity in frontal cortex. However, neural and behavioral adaptations can occur at multiple time scales, and their relationship remains poorly defined. Here, we developed a novel adaptive sensorimotor decision-making task for head-fixed mice, requiring them to shift flexibly between multiple auditory-motor mappings. Two-photon calcium imaging of secondary motor cortex (M2) revealed different ensemble activity states for each mapping. Notably, when adapting to a conditional mapping, transitions in ensemble activity were abrupt and occurred before the recovery of behavioral performance. By contrast, gradual and delayed transitions accompanied shifts towards repetitive responding. These results demonstrate distinct ensemble signatures associated with the start versus end of sensory-guided behavior, and suggest that M2 leads in engaging goal-directed response strategies that require sensorimotor associations.

Motor activity is often initiated by a population of command-like interneurons. Command-like interneurons that reliably drive programs have received the most attention, so little is known about how less reliable command-like interneurons may contribute to program generation. We study two electrically coupled interneurons, cerebral-buccal interneuron-2 (CBI-2) and CBI-11, which activate feeding motor programs in the mollusk Aplysia californica. Earlier work indicated that, in rested preparations, CBI-2, a powerful activator of programs, can trigger ingestive and egestive programs. CBI-2 reliably generated ingestive patterns only when it was repeatedly stimulated. The ability of CBI-2 to trigger motor activity has been attributed to the two program-promoting peptides it contains, FCAP and CP2. Here, we show that CBI-11 differs from CBI-2 in that it contains FCAP but not CP2. Furthermore, it is weak in its ability to drive programs. On its own, CBI-11 is therefore less effective as a program activator. When it is successful, however, CBI-11 is an effective specifier of motor activity; that is, it drives mostly ingestive programs. Importantly, we found that CBI-2 and CBI-11 complement each other's actions. First, prestimulation of CBI-2 enhanced the ability of CBI-11 to drive programs. This effect appears to be partly mediated by CP2. Second, coactivation of CBI-11 with CBI-2 makes CBI-2 programs immediately ingestive. This effect may be mediated by specific actions that CBI-11 exerts on pattern-generating interneurons. Therefore, different classes of command-like neurons in a motor network may make distinct, but potentially complementary, contributions as either activators or specifiers of motor activity.

Behavior is a product of both the stimuli encountered and the current internal state. At the level of the nervous system, the internal state alters the biophysical properties of, and connections between, neurons establishing a “network state”. To establish a network state, the nervous system must be altered from an initial default/resting state, but what remains unclear is the extent to which this process represents induction from a passive default state or the removal of suppression by an active default state. We use repetition priming (a history-dependent improvement of behavioral responses to repeatedly encountered stimuli) to determine the cellular mechanisms underlying the transition from the default to the primed network state. We demonstrate that both removal of active suppression and induction of neuron excitability changes each contribute separately to the production of a primed state. The feeding system of Aplysia californica displays repetition priming via an increase in the activity of the radula closure neuron B8, which results in increased bite strength with each motor program. We found that during priming, B8 received progressively less inhibitory input from the multi-functional neurons B4/5. Additionally, priming enhanced the excitability of B8, but the rate at which B8 activity increased as a result of these changes was regulated by the progressive removal of inhibitory input. Thus, the establishment of the network state involves the induction of processes from a rested state, yet the consequences of these processes are conditional upon critical gating mechanisms actively enforced by the default state.

Instrumental behavior is characterized by the selection of actions based on the degree to which they lead to a desired outcome. However, we lack a detailed understanding of how rewarded actions are reinforced and preferentially implemented. In rodents, the medial frontal cortex is hypothesized to play an important role in this process, based in part on its capacity to encode chosen actions and their outcomes. We therefore asked how neural representations of choice and outcome might interact to facilitate instrumental behavior. To investigate this question, we imaged neural ensemble activity in layer 2/3 of the secondary motor region (M2) while mice engaged in a two-choice auditory discrimination task with probabilistic outcomes. Correct choices could result in one of three reward amounts (single, double or omitted reward), which allowed us to measure neural and behavioral effects of reward magnitude, as well as its categorical presence or absence. Single-unit and population decoding analyses revealed a consistent influence of outcome on choice signals in M2. Specifically, rewarded choices were more robustly encoded relative to unrewarded choices, with little dependence on the exact magnitude of reinforcement. Our results provide insight into the integration of past choices and outcomes in the rodent brain during instrumental behavior.