Contextual gating of motivationally-relevant stimuli in the mouse nucleus accumbens

Neural activity in the nucleus accumbens (NAc) is thought to track fundamentally value- centric quantities such as current or future expected reward, reward prediction errors, the value of work, opportunity cost, and approach vigor. However, the NAc also contributes to flexible behavior in ways that are difficult to explain based on value signals alone, raising the question of if and how non-value signals are encoded in NAc. We recorded NAc neural ensembles while head-fixed mice performed a context-dependent odor discrimination task, and extracted single-unit and population-level correlates of task features. We found coding for context-setting cues that modulate the stimulus-outcome association of subsequently presented reward-predictive cues. This context signal occupied a subspace orthogonal to classic value representations, suggesting that it does not interfere with value-related NAc output. Finally, we show that the context signal is predictive of subsequent value coding, supporting a circuit-level gating model for how the NAc contributes to behavioral flexibility and providing a novel population-level perspective from which to view NAc computations.

A Neural Mechanism of Cue-Outcome Expectancy Generated by the Interaction Between Orbitofrontal Cortex and Amygdala

Taste perception is important for animals to take adequate nutrients and avoid toxins for their survival. Appetitive and aversive behaviors are produced by value evaluation of taste and taste expectation caused by other sensations. The value evaluation, coupled with a cue presentation, produces outcome expectation and guides flexible behaviors when the environment is changed. Experimental studies demonstrated distinct functional roles of basolateral amygdala (ABL) and orbitofrontal cortex (OFC) in value evaluation and adaptive behavior. ABL is involved in generating a cue–outcome association, whereas OFC makes a contribution of generating a cue-triggered expectation to guide adaptive behavior. However, it remains unclear how ABL and OFC form their functional roles, with the learning of adaptive behavior. To address this issue, we focus on an odor discrimination task of rats and develop a computational model that consists of OFC and ABL, interacting with reward and decision systems. We present the neural mechanisms underlying the rapid formation of cue–outcome association in ABL and late behavioral adaptation mediated by OFC. Moreover, we offer 2 functions of cue-selective neurons in OFC: one is that the activation of cue-selective neurons transmits value information to decision area to guide behavior and another is that persistent activity of cue-selective neurons evokes a weak activity of taste-sensitive OFC neurons, leading to cue-outcome expectation. Our model further accounts for ABL and OFC responses caused by lesions of these areas. The results provide a computational framework of how ABL and OFC are functionally linked through their interactions with the reward and decision systems.

Rapid olfactory discrimination learning in adult zebrafish

The zebrafish is a model organism to study olfactory information processing but efficient behavioral procedures to analyze olfactory discrimination and memory are lacking. We devised an automated odor discrimination task for adult zebrafish based on olfactory conditioning of feeding behavior. Presentation of a conditioned odor (CS+), but not a neutral odor (CS-), was followed by food delivery at a specific location. Fish developed differential behavioral responses to CS+ and CS- within a few trials even when odors were similar. The behavioral response to the CS+ was complex and included components reminiscent of food search such as increased swimming speed and water surface sampling. Appetitive behavior was therefore quantified by a composite score that combined measurements of multiple behavioral parameters. Discrimination behavior was robust in different strains and learned preferences could overcome innate odor preferences. These results confirm that zebrafish can rapidly learn to make fine odor discriminations. The procedure is efficient and provides novel opportunities to dissect the neural mechanisms underlying olfactory discrimination and memory.

The Habituation/Cross-Habituation Test Revisited: Guidance from Sniffing and Video Tracking

The habituation/cross-habituation test (HaXha) is a spontaneous odor discrimination task that has been used for many decades to evaluate olfactory function in animals. Animals are presented repeatedly with the same odorant after which a new odorant is introduced. The time the animal explores the odor object is measured. An animal is considered to cross-habituate during the novel stimulus trial when the exploration time is higher than the prior trial and indicates the degree of olfactory patency. On the other hand, habituation across the repeated trials involves decreased exploration time and is related to memory patency, especially at long intervals. Classically exploration is timed using a stopwatch when the animal is within 2 cm of the object and aimed toward it. These criteria are intuitive, but it is unclear how they relate to olfactory exploration, that is, sniffing. We used video tracking combined with plethysmography to improve accuracy, avoid observer bias, and propose more robust criteria for exploratory scoring when sniff measures are not available. We also demonstrate that sniff rate combined with proximity is the most direct measure of odorant exploration and provide a robust and sensitive criterion.