Nejvíce citovaný článek - PubMed ID 9368940
Dissociation of exteroceptive and idiothetic orientation cues: effect on hippocampal place cells and place navigation
It is well known that communication between the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC) is critical for various cognitive and behavioral functions. However, the exact role of these structures in spatial coordination remains to be clarified. Here we sought to determine the involvement of the mPFC and the vHPC in the spatial retrieval of a previously learned active place avoidance task in adult male Long-Evans rats, using a combination of unilateral and bilateral local muscimol inactivations. Moreover, we tested the role of the vHPC-mPFC pathway by performing combined ipsilateral and contralateral inactivations. Our results showed not only bilateral inactivations of either structure, but also the combined inactivations impaired the retrieval of spatial memory, whereas unilateral one-structure inactivations did not yield any effect. Remarkably, muscimol injections in combined groups exerted similar deficits, regardless of whether the inactivations were contralateral or ipsilateral. These findings confirm the importance of these structures in spatial cognition and emphasize the importance of the intact functioning of the vHPC-mPFC pathway.
- Klíčová slova
- active place avoidance, hippocampo-prefrontal pathway, muscimol, rotating arena, spatial memory,
- MeSH
- hipokampus * MeSH
- krysa rodu Rattus MeSH
- muscimol farmakologie MeSH
- potkani Long-Evans MeSH
- prefrontální mozková kůra MeSH
- prostorová paměť * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- muscimol MeSH
The active place avoidance task is a dry-arena task used to assess spatial navigation and memory in rodents. In this task, a subject is put on a rotating circular arena and avoids an invisible sector that is stable in relation to the room. Rotation of the arena means that the subject's avoidance must be active, otherwise the subject will be moved in the to-be-avoided sector by the rotation of the arena and a slight electric shock will be administered. The present experiment explored the effect of variable arena rotation speed on the ability to avoid the to-be-avoided sector. Subjects in a group with variable arena rotation speed learned to avoid the sector with the same speed and attained the same avoidance ability as rats in a group with a stable arena rotation speed. Only a slight difference in preferred position within the room was found between the two groups. No difference was found between the two groups in the dark phase, where subjects could not use orientation cues in the room. Only one rat was able to learn the avoidance of the to-be-avoided sector in this phase. The results of the experiment suggest that idiothetic orientation and interval timing are not crucial for learning avoidance of the to-be-avoided sector. However, idiothetic orientation might be sufficient for avoiding the sector in the dark.
- Klíčová slova
- Inertial idiothetic navigation, Interval timing, Rats, Spatial navigation, Substratal idiothetic navigation,
- Publikační typ
- časopisecké články MeSH
Patients with schizophrenia often manifest deficits in behavioral flexibility. Non-competitive NMDA receptor antagonists such as MK-801 induce schizophrenia-like symptoms in rodents, including cognitive functions. Despite work exploring flexibility has been done employing behavioral paradigms with simple stimuli, much less is known about what kinds of flexibility are affected in an MK-801 model of schizophrenia-like behavior in the spatial domain. We used a rotating arena-based apparatus (Carousel) requiring rats to avoid an unmarked sector defined in either the reference frame of the rotating arena (arena frame task, AF) or the stationary room (room frame task, RF). We investigated behavioral flexibility in four conditions involving different cognitive loads. Each condition encompassed an initial (five sessions) and a test phase (five sessions) in which some aspects of the task were changed to test flexibility and in which rats were given saline, 0.05 mg/kg or 0.1 mg/kg MK-801 thirty minutes prior to a session. In the first condition, rats acquired avoidance in RF with clockwise rotation of the arena while in the test phase the arena rotated counterclockwise. In the second condition, rats initially acquired avoidance in RF with the sector on the north and then it was reversed to south (spatial reversal). In the third and fourth conditions, rats initially performed an AF (RF, respectively) task, followed by an RF (AF, respectively) task, testing the ability of cognitive set-shifting. We found no effect of MK-801 either on simple motor adjustment after reversal of arena rotation or on spatial reversal within the RF. In contrast, administration of MK-801 at a dose of 0.1 mg/kg interfered with set-shifting in both conditions. Furthermore, we observed MK-801 0.1 mg/kg elevated locomotion in all cases. These data suggest that blockade of NMDA receptors by acute system administration of MK-801 preferentially affects set-shifting in the cognitive domain rather than reversal.
- Klíčová slova
- Carousel, MK-801, cognitive flexibility, rat, reversal, schizophrenia, set-shifting,
- Publikační typ
- časopisecké články MeSH
Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena - Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated neurons.
- Klíčová slova
- arc, carousel, cognitive coordination, hippocampus, homer 1a, place avoidance, rotating arena, schizophrenia,
- Publikační typ
- časopisecké články MeSH
Hippocampal activity is thought to encode spatial representations in a distributed associative network. This idea predicts that partial hippocampal lesions would spare acquisition and impair retrieval of a place response as long as enough connections remained intact to encode associations. Water maze experiments supported the predictions, but the prediction of impaired retrieval was not supported when tetrodotoxin (TTX) was injected into one hippocampus and rats were tested in a place avoidance task on a rotating arena with shallow water. The rotation dissociated relevant distal stimuli from irrelevant self-motion stimuli. To explain the discrepancy, we hypothesized that the segregation of relevant and irrelevant stimuli and stimuli association into representations are distinct hippocampus-dependent operations, and whereas associative representation is more sensitive to disruption during retrieval than learning, stimulus segregation is more sensitive to disruption during learning than during retrieval. The following predictions were tested: (1) the TTX injection would spare learning but (2) impair retrieval of a place response in the water maze, which has a high associative representational demand but a low demand for segregation; (3) the injection would impair learning but (4) spare retrieval of place avoidance in the rotating arena filled with water, which has a high demand for stimulus segregation but a low associative representational demand. All four predictions were confirmed. The hypothesis also explains the pattern of sparing and impairment after the TTX injection in other place avoidance task variants, leading us to conclude that stimulus separation and association representation are dissociable functions of the hippocampus.
- MeSH
- analýza rozptylu MeSH
- anestetika lokální toxicita MeSH
- bludiště - učení účinky léků fyziologie MeSH
- časové faktory MeSH
- chování zvířat MeSH
- hipokampus účinky léků zranění fyziologie MeSH
- krysa rodu Rattus MeSH
- poruchy paměti chemicky indukované patofyziologie MeSH
- potkani Long-Evans MeSH
- rozpomínání účinky léků fyziologie MeSH
- tetrodotoxin toxicita MeSH
- učení vyhýbat se účinky léků fyziologie MeSH
- úniková reakce účinky léků fyziologie MeSH
- vnímání prostoru účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- anestetika lokální MeSH
- tetrodotoxin MeSH
The present study describes a task testing the ability of rats to trigger operant behavior by their relative spatial position to inaccessible rotating objects. Rats were placed in a Skinner box with a transparent front wall through which they could observe one or two adjacent objects fixed on a slowly rotating arena (d = 1 m) surrounded by an immobile black cylinder. The direction of arena rotation was alternated at a sequence of different time intervals. Rats were reinforced for the first bar-press that was emitted when a radius separating the two adjacent objects or dividing a single object into two halves (pointing radius) entered a 60 degrees sector of its circular trajectory defined with respect to the stationary Skinner box (reward sector). Well trained rats emitted 62.1 +/- 3.6% of responses in a 60 degrees sector preceding the reward sector and in the first 30 degrees of the reward sector. Response rate increased only when the pointing radius was approaching the reward sector, regardless of the time elapsed from the last reward. In the extinction session, when no reward was delivered, rats responded during the whole passage of the pointing radius through the former reward sector and spontaneously decreased responding after the pointing radius left this area. This finding suggests that rats perceived the reward sector as a continuous single region. The same results were obtained when the Skinner box with the rat was orbiting around the immobile scene. It is concluded that rats can recognize and anticipate their position relative to movable objects.
The spatial orientation of vertebrates is implemented by two complementary mechanisms: allothesis, processing the information about spatial relationships between the animal and perceptible landmarks, and idiothesis, processing the substratal and inertial information produced by the animal's active or passive movement through the environment. Both systems allow the animal to compute its position with respect to perceptible landmarks and to the already traversed portion of the path. In the present study, we examined the properties of substratal idiothesis deprived of relevant exteroceptive information. Rats searching for food pellets in an arena formed by a movable inner disk and a peripheral immobile belt were trained in darkness to avoid a 60 degrees sector; rats that entered this sector received a mild foot shock. The punished sector was defined in the substratal idiothetic frame, and the rats had to determine the location of the shock sector with the use of substratal idiothesis only, because all putative intramaze cues were made irrelevant by angular displacements of the disk relative to the belt. Striking impairment of place avoidance by this "shuffling procedure" indicates that effective substratal idiothesis must be updated by exteroceptive intramaze cues.
- MeSH
- krysa rodu Rattus MeSH
- plnění a analýza úkolů MeSH
- podněty * MeSH
- potkani Long-Evans MeSH
- prostorové chování * MeSH
- reverzní učení MeSH
- učení vyhýbat se MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Continuous rotation of an arena in a cue-rich room dissociates the stationary room-bound information from the rotating arena-bound information. This disrupted spatial discharge in the majority of place cells from rats trained to collect randomly scattered food. In contrast, most place cell firing patterns recorded from rats trained to solve a navigation task on the rotating arena were preserved during the rotation. Spatial discharge was preserved in both the task-relevant stationary and the task-irrelevant rotating reference frames, but firing was more organized in the task-relevant frame. It is concluded that, (i) the effects of environmental manipulations can be understood with confidence only when the rat's purposeful behavior is used to formulate interpretations of the data, and (ii) hippocampal place cell activity is organized in multiple overlapping spatial reference frames.
Foraging rats learned to avoid footshock that was present in a part of a circular arena that was either stable or rotating slowly in a lighted room. The rotation dissociated spatial information in the separate reference frames of the room and arena. After learning to avoid the shocked region in either condition, in the absence of shock, memory for this place was expressed by simultaneous avoidance of an area defined in the reference frame of the room as well as of an area defined in the reference frame of the rotating arena. Spatial memories in these distinct reference frames were acquired, retrieved, and extinguished autonomously.
- MeSH
- časové faktory MeSH
- chování zvířat fyziologie MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- paměť fyziologie MeSH
- prostorové chování fyziologie MeSH
- světlo MeSH
- učení vyhýbat se MeSH
- zraková percepce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
