Pharmacological intervention in the substantia nigra is known to induce repetitive behaviors in rodents, but a direct causal relationship between a specific neural circuit and repetitive behavior has not yet been established. Here we demonstrate that optogenetic activation of dopamine D1 receptor-expressing MSNs terminals in the substantia nigra pars reticulata resulted in sustained and chronic repetitive behaviors. These data show for the first time that activation of the striatonigral direct pathway is sufficient to generate motor stereotypies.

Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-o-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using beta 2-microglobulin knock-out (Pm KO) mice, which lack hippocampal asymmetry. We tested beta 2m KO mice in a series of spatial and non-spatial learning tasks and compared the performances of beta 2m KO and C57BL6/J wild-type (WT) mice. The beta 2m KO mice appeared normal in both spatial reference memory and spatial working memory tasks but they took more time than WT mice in learning the two non-spatial learning tasks (i.e., a differential reinforcement of lower rates of behavior (DRL) task and a straight runway task). The beta 2m KO mice also showed less precision in their response timing in the DRL task and showed weaker spontaneous recovery during extinction in the straight runway task. These results indicate that hippocampal asymmetry is important for certain characteristics of non spatial learning.

In three experiments, the nature of the interaction between multiple memory systems in rats solving a variation of a spatial task in the water maze was investigated. Throughout training rats were able to find a submerged platform at a fixed distance and direction from an intramaze landmark by learning a landmark-goal vector. Extramaze cues were also available for standard place learning, or “cognitive mapping,” but these cues were valid only within each session, as the position of the platform moved around the pool between sessions together with the intramaze landmark. Animals could therefore learn the position of the platform by taking the consistent vector from the landmark across sessions or by rapidly encoding the new platform position on each session with reference to the extramaze cues. Excitotoxic lesions of the dorsolateral striatum impaired vector-based learning but facilitated cognitive map-based rapid place learning when the extramaze cues were relatively poor (Experiment 1) but not when they were more salient (Experiments 2 and 3). The way the lesion effects interacted with cue availability is consistent with the idea that the memory systems involved in the current navigation task are functionally cooperative yet associatively competitive in nature.

The effects of stimulus salience and cue validity in the overshadowing of geometric features of an enclosed arena by discrete landmarks were investigated in rats using the water maze paradigm. Experiment 1 established that in h rhomboid-shaped arena, the acute corner was more salient than the obtuse corner. In Experiment 2, rats were trained to find a submerged platform either in one of the acute, or obtuse, corners. In addition to the information provided by corner angle, the platform was also signaled by the presence of a spherical landmark suspended above the platform for rats in the experimental group. The landmark was a more valid cue for predicting the location of the platform than the angle of the corner. This training resulted in overshadowing of learning about the angle of the corner by the presence of the landmark. The final experiment extended this result by showing that when the predictive validities of the angle and the landmark were matched in the experimental group, learning about geometry was still overshadowed by the presence of landmarks, but only in animals that were trained with the platform at an obtuse, but not acute, corner. These results uniquely demonstrate that learning about geometry can be overshadowed by discrete landmarks, and also that whether overshadowing is observed depends on the stimulus salience and the relative validity of the competing cues. These findings imply that learning based on geometric cues follows the same basic rules that apply to a wide range of other learning paradigms.

Different groups of rats received different amounts of training to lever press for a food reinforcer before an aversion was conditioned to the food. This devaluation of the reinforcer reduced responding in both subsequent extinction and reinforced tests of responding to a degree that was independent of the amount of instrumental training. Moreover, interpolating context extinction between aversion conditioning and the extinction test reduced the magnitude of the devaluation effect, thereby indicating that Pavlovian contextual conditioning may play a role in the instrumental devaluation effect. (C) 2010 Elsevier B.V. All rights reserved.

The capacity for goal-directed behavior requires not only the encoding of the response-outcome relationship but also the ability to resolve conflict induced by competing responses. Recent neuroimaging studies have identified the prefrontal cortex as critical for resolving conflict between competing responses. At present, however, much of this evidence is indirect, and the necessity of dorsomedial prefrontal cortex (dmPFC) function for the resolution of conflict in goal-directed behavior has not been assessed. Here, we develop a rodent paradigm to investigate response conflict caused by the concurrent activation of a correct and incorrect response. In this paradigm, the outcome of one response also acts as a discriminative stimulus signaling that the other response is correct. Whereas rats with a functional dmPFC are able to resolve this conflict, inactivation of dmPFC using an infusion of muscimol produced a deficit by selectively interfering with their ability to inhibit the incorrect, competing response.