Although the nucleus accumbens (NAc) has long been hypothesized to act as an interface between limbic and motor regions, direct evidence for this modulatory role on behavior is lacking. Using a disconnection procedure in rats, we found that basolateral amygdala (BLA) input to the core and medial shell of the NAc separately mediate two distinct incentive processes controlling the performance of goal-directed, instrumental actions, respectively: (1) the sensitivity of instrumental responding to changes in the experienced value of the goal or outcome, produced by specific satiety-induced outcome devaluation, and (2) the effect of reward-related cues on action selection, observed in outcome-specific Pavlovian-instrumental transfer. These results reveal, therefore, that dissociable neural circuits involving BLA inputs to the NAc core and medial shell mediate distinct components of the incentive motivational processes controlling choice and decision-making in instrumental conditioning.

The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction.

The performance of goal-directed actions relies on an animal's previous knowledge of the outcomes or consequences that result from its actions. Additionally, a sensorimotor learning process linking environmental stimuli with actions influences instrumental performance by selecting actions for additional evaluation. These distinct decision-making processes in rodents depend on separate subregions of the dorsal striatum. Whereas the posterior dorsomedial striatum (pDMS) is required for the encoding of actions with their outcomes or consequences, the dorsolateral striatum (DLS) mediates action selection based on sensorimotor learning. However, the molecular mechanisms within these brain regions that support learning and performance of goal-directed behavior are not known. Here we show that activation of extracellular signal-regulated kinase (ERK) in the dorsal striatum has a critical role in learning and performance of instrumental goal-directed behavior in rodents. We observed an increase in p42 ERK (ERK2) activation in both the pDMS and DLS during both the acquisition and performance of recently acquired instrumental goal-directed actions. Furthermore, disruption of ERK activation in the pDMS prevented both the acquisition of action-outcome associations, as well as the performance of goal-directed actions guided by previously acquired associations, whereas disruption of ERK activation in the DLS disrupted instrumental performance but left instrumental action-outcome learning intact. These results provide evidence of a critical, region-specific role for ERK signaling in the dorsal striatum during the acquisition of instrumental learning and suggest that processes sensitive to ERK signaling within these striatal subregions interact to control instrumental performance after initial acquisition.

The volume of the hippocampal formation (HF) in black-capped chickadees (Poecile atricapillus) varies across the seasons, in parallel with the seasonal cycle in food hoarding. In this study, we estimate cell density and total cell number in the HF across seasons in both juveniles and adults. We find that the seasonal variation in volume is due to an increase in the number of small and large cells (principally neurons) in the fall. Adults also have lower neuron densities than juveniles. Both juveniles and adults show an increase in cell density in the rostral part of the HF in August and a subsequent decrease toward October. This suggests that the net cell addition to the HF may already start in August. We discuss the implications of this early start with respect to the possibility that the seasonal change in HF volume is driven by the experience of food hoarding. We also speculate on the functional significance of the addition of neurons to the HF in the fall.

The motivation to seek out rewards can come under the control of stimuli associated with reward delivery. The ability of cues to motivate reward-seeking behavior depends on the nucleus accumbens (NAcc). The molecular mechanisms in the NAcc that underlie the ability of a cue to motivate reward-seeking are not well understood. We examined whether extracellular signal-regulated kinase (ERK), an important intracellular signaling pathway in learning and memory, has a role in these motivational processes. We first examined p42 ERK (ERK2) activation in the NAcc after rats were trained to associate an auditory stimulus with food delivery and found that, as a consequence of training, presentation of the auditory cue itself was sufficient to increase ERK2 activation in the NAcc. To examine whether inhibition of ERK in the NAcc prevents cue-induced reward-seeking, we infused an inhibitor of ERK, U0126, into the NAcc before assessing rats' instrumental responding in the presence versus absence of the conditioned cue. We found that, whereas vehicle-infused rats showed increased instrumental responding during cue presentation, rats infused with U0126 showed a profound impairment in cue-induced instrumental responding. In contrast, intra-NAcc U0126 infusion had no effect on rats' food-reinforced instrumental responding or their ability to execute conditioned approach behavior. Our results demonstrate learning-related changes in ERK signaling in the NAcc, and that disruption of ERK activation in this structure interferes with the incentive-motivational effects of conditioned stimuli. The molecular mechanisms described here may have implications for cue-elicited drug craving after repeated exposure to drugs of abuse.