Interval schedules of reinforcement are known to generate habitual behavior, the performance of which is less sensitive to revaluation of the earned reward and to alterations in the action-outcome contingency. Here we report results from experiments using different types of interval schedules of reinforcement in mice to assess the effect of uncertainty, in the time of reward availability, on habit formation. After limited training, lever pressing under fixed interval (FI, low interval uncertainty) or random interval schedules (RI, higher interval uncertainty) was sensitive to devaluation, but with more extended training, performance of animals trained under RI schedules became more habitual, i.e. no longer sensitive to devaluation, whereas performance of those trained under FI schedules remained goal-directed. When the press-reward contingency was reversed by omitting reward after pressing but presenting reward in the absence of pressing, lever pressing in mice previously trained under FI decreased more rapidly than that of mice trained under RI schedules. Further analysis revealed that action-reward contiguity is significantly reduced in lever pressing under RI schedules, whereas action-reward correlation is similar for the different schedules. Thus the extent of goal-directedness could vary as a function of uncertainty about the time of reward availability. We hypothesize that the reduced action-reward contiguity found in behavior generated under high uncertainty is responsible for habit formation.

A 2A receptors are a major class of G-protein-coupled receptors for adenosine. Highly expressed in the striatum, on the projection neurons giving rise to the striatopallidal or "indirect" pathway, they have been implicated in sleep, addiction, and other processes, yet their role in the control of striatal circuits and behavior remains unclear. Using established assays from the instrumental learning paradigm, we showed that mice with striatum-specific deletion of A 2A receptors were selectively impaired in habit formation. After training that generated habitual lever pressing in wild-type controls, the performance of striatum-specific A 2A knock-out mice remained goal directed, being highly sensitive to outcome devaluation and reversal of the action-outcome contingency. These data demonstrate a critical role for A 2A receptors on striatopallidal medium spiny projection neurons in shaping behavior and decision making, providing the first instance of a selective alteration in instrumental learning after striatum-specific genetic manipulations.

The mediodorsal thalamus (MD) is a crucial component of the neural network involved in the learning and generation of goal-directed actions. A series of experiments reported here examined the contributions of MD to the temporal differentiation of reward-guided actions. In Experiment 1, we trained rats on a discrete-trial, fixed-criterion temporal differentiation task, in which only lever presses exceeding a threshold duration value were rewarded. Pre-training MD lesions impaired temporal differentiation of action duration, by increasing the dispersion of the duration distribution. Post-training MD lesions also impaired differentiation, but by reducing the average emitted press durations, thus shifting the distribution without increasing the dispersion. In Experiment 2, we trained rats to space their lever pressing above criterion inter-press-intervals in order to earn rewards. Both pre-training and post-training MD lesions impaired the differentiation of inter-press-intervals. These results show that MD plays an important role in the acquisition and expression of action differentiation.

No abstract

Cracking the cytoarchitectural organization, activity patterns, and neurotransmitter nature of genetically-distinct cell types in the lateral hypothalamus (LH) is fundamental to develop a mechanistic understanding of how activity dynamics within this brain region are generated and operate together through synaptic connections to regulate circuit function. However, the precise mechanisms through which LH circuits orchestrate such dynamics have remained elusive due to the heterogeneity of the intermingled and functionally distinct cell types in this brain region. Here we reveal that a cell type in the mouse LH identified by the expression of the calcium-binding protein parvalbumin (PVALB; LHPV) is fast-spiking, releases the excitatory neurotransmitter glutamate, and sends long range projections throughout the brain. Thus, our findings challenge long-standing concepts that define neurons with a fast-spiking phenotype as exclusively GABAergic. Furthermore, we provide for the first time a detailed characterization of the electrophysiological properties of these neurons. Our work identifies LHPV neurons as a novel functional component within the LH glutamatergic circuitry.