Replay of Behavioral Sequences in the Medial Prefrontal Cortex during Rule Switching.

Temporally organized reactivation of experiences during awake immobility periods is thought to underlie cognitive processes like planning and evaluation. While replay of trajectories is well established for the hippocampus, it is unclear whether the medial prefrontal cortex (mPFC) can reactivate sequential behavioral experiences in the awake state to support task execution. We simultaneously recorded from hippocampal and mPFC principal neurons in rats performing a mPFC-dependent rule-switching task on a plus maze. We found that mPFC neuronal activity encoded relative positions between the start and goal. During awake immobility periods, the mPFC replayed temporally organized sequences of these generalized positions, resembling entire spatial trajectories. The occurrence of mPFC trajectory replay positively correlated with rule-switching performance. However, hippocampal and mPFC trajectory replay occurred independently, indicating different functions. These results demonstrate that the mPFC can replay ordered activity patterns representing generalized locations and suggest that mPFC replay might have a role in flexible behavior. VIDEO ABSTRACT.

The role of rat posterior parietal cortex in coordinating spatial representations during place avoidance in dissociated reference frames on a continuously rotating arena (Carousel).

On the Carousel maze, rats are trained to avoid a sector of a circular rotating arena, punishable by a mild electric foot-shock. In the room frame (RF) variant, the punishable sector remains stable relative to the room, while in the arena frame (AF) version, the sector rotates with the arena. The rats therefore need to disregard local olfactory, tactile and self-motion cues in RF condition and distal extra-maze landmarks in the AF task. In both primates and rodents, the coordination of various spatial reference frames is thought to depend on the posterior parietal cortex (PPC). We have previously shown that PPC-lesioned rats can solve both variants of the Carousel avoidance task. Here we aimed to determine the effects of bilateral thermocoagulation lesion of the PPC in Long-Evans rats on the ability to transition between multiple spatial strategies. The rats were first trained in five sessions in one condition and then another five sessions in the other. The following training schemes were used: RF to AF, RF to RF reversal (sector on the opposite side), and AF to RF. We found a PPC lesion-associated impairment in the transition from the AF to RF task, but not vice versa. Furthermore, PPC lesion impaired performance in RF reversal. In accordance to the literature, we also found an impairment in navigation guided by intra-maze visuospatial cues, but not by extra-maze cues in the water maze. Therefore, the PPC lesion-induced impairment is neither specific to distant cues nor to allocentric processing. Our results thus indicate a role of the PPC in the flexibility in spatial behaviors guided by visual orientation cues.

Functional inactivation of the rat hippocampus disrupts avoidance of a moving object.

The hippocampus is well known for its critical involvement in spatial memory and information processing. In this study, we examined the effect of bilateral hippocampal inactivation with tetrodotoxin (TTX) in an "enemy avoidance" task. In this paradigm, a rat foraging on a circular platform (82 cm diameter) is trained to avoid a moving robot in 20-min sessions. Whenever the rat is located within 25 cm of the robot's center, it receives a mild electrical foot shock, which may be repeated until the subject makes an escape response to a safe distance. Seventeen young male Long-Evans rats were implanted with cannulae aimed at the dorsal hippocampus 14 d before the start of the training. After 6 d of training, each rat received a bilateral intrahippocampal infusion of TTX (5 ng in 1 µL) 40 min before the training session on day 7. The inactivation severely impaired avoidance of a moving robot (n = 8). No deficit was observed in a different group of rats (n = 9) that avoided a stable robot that was only displaced once in the middle of the session, showing that the impairment was not due to a deficit in distance estimation, object-reinforcement association, or shock sensitivity. This finding suggests a specific role of the hippocampus in dynamic cognitive processes required for flexible navigation strategies such as continuous updating of information about the position of a moving stimulus.

Inertial stimuli generated by arena rotation are important for acquisition of the active place avoidance task.

The active place avoidance task is used for testing cognitive abilities in rats. A rat, placed on a rotating circular arena, should avoid an unmarked sector defined with respect to stable extra-arena cues. We hypothesized that the inertial stimuli generated by the arena rotation may contribute to the performance in the task. These stimuli provide permanent information to the rat concerning changes in its position with respect to the extra-arena cues, it means to the reference frame in which the to-be-avoided sector is defined. To test the hypothesis, we trained one group of rats on a stable arena while extra-arena cues rotated around the arena. This eliminated the inertial stimuli generated by the arena rotation while preserving other aspects of the task. Six out of seven rats from this group did not learn this modified task. The remaining rat learned it equally well as rats from a control group learned the standard active place avoidance task. After six days of training, we changed the tasks between the groups. The control rats solved the modified task as well as the standard task. We conclude that the inertial stimuli generated by the arena rotation are important for acquisition of the active place avoidance task but not for performance once the task has been mastered. We suggest that rats must perceive the distal extra-arena cues as stable in order to associate the position of the to-be-avoided sector with these cues.

Enemy avoidance task: a novel behavioral paradigm for assessing spatial avoidance of a moving subject.

Navigation with respect to moving goals represents a useful ability in the everyday life of animals. We have developed a novel behavioral paradigm, "enemy avoidance task", in which a laboratory rat (subject) was trained to avoid another rat (enemy), while searching for small pasta pellets dispensed onto an experimental arena. Whenever the distance between the two animals was smaller than 25 cm, the subject was given a mild electric footshock. The results have shown that rats are capable of avoiding another rat while exploring an environment. Therefore, the enemy avoidance task can be used in electrophysiological, lesion or neuropharmacological studies exploring neuronal substrate coding for egocentric and allocentric positions of an observed animal.

Lesion of posterior parietal cortex in rats does not disrupt place avoidance based on either distal or proximal orienting cues.

A current topic in neurobiology is the study of the role of various brain structures in processing of spatial information. The present study was aimed at elucidating the role of the rat posterior parietal cortex in performing a place avoidance task. Two variants of the task were used: an arena frame task, in which animals were trained to avoid a sector defined by local cues bound to the surface of a rotating arena, and the room frame task, in which the shock sector was defined with respect to distal room landmarks. The results showed that both control and lesioned rats were able to efficiently solve both tasks, while locomotion was not altered. These results suggest that the posterior parietal cortex is not crucial for the processing of either proximal or distal cues in place avoidance.