Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice) is always followed by a small reward. Pressing the other lever (risky choice) is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices.

To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneously, as rats learned to press a lever to earn food rewards. In both MD and mPFC, instrumental learning was accompanied by dramatic changes in the firing patterns of the neurons, in particular the rapid emergence of single-unit neural activity reflecting the completion of the action and reward delivery. In addition, we observed distinct patterns of changes in the oscillatory LFP response in MD and mPFC. With learning, there was a significant increase in theta band oscillations (6-10 Hz) in the MD, but not in the mPFC. By contrast, gamma band oscillations (40-55 Hz) increased in the mPFC, but not in the MD. Coherence between these two regions also changed with learning: gamma coherence in relation to reward delivery increased, whereas theta coherence did not. Together these results suggest that, as rats learned the instrumental contingency between action and outcome, the emergence of task related neural activity is accompanied by enhanced functional interaction between MD and mPFC in response to the reward feedback.

A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA) neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra.

We examined the contribution of the nigrostriatal DA system to instrumental learning and behavior using optogenetics in awake, behaving mice. Using Cre-inducible channelrhodopsin-2 (ChR2) in mice expressing Cre recombinase driven by the tyrosine hydroxylase promoter (Th-Cre), we tested whether selective stimulation of DA neurons in the substantia nigra pars compacta (SNC), in the absence of any natural rewards, was sufficient to promote instrumental learning in naive mice. Mice expressing ChR2 in SNC DA neurons readily learned to press a lever to receive laser stimulation, but unlike natural food rewards the lever pressing did not decline with satiation. When the number of presses required to receive a stimulation was altered, mice adjusted their rate of pressing accordingly, suggesting that the rate of stimulation was a controlled variable. Moreover, extinction, i.e. the cessation of action-contingent stimulation, and the complete reversal of the relationship between action and outcome by the imposition of an omission contingency, rapidly abolished lever pressing. Together these results suggest that selective activation of SNC DA neurons can be sufficient for acquisition and maintenance of a new instrumental action.