Nejvíce citovaný článek - PubMed ID 21402943
Functional inactivation of the rat hippocampus disrupts avoidance of a moving object
Animals and humans receive the most critical information from parts of the environment that are immediately inaccessible and highly dynamic. The brain must effectively process potential interactions between elements in such an environment to make appropriate decisions in critical situations. We trained male Long-Evans rats to discriminate static and dynamic spatial stimuli and to generalize novel dynamic spatial stimuli displayed on an inaccessible computer screen. We provide behavioral evidence indicating that rats encode dynamic visuospatial situations by constructing internal static representations that capture meaningful future interactions between objects. These observations support previous findings in humans that such internal static representations can encapsulate relevant spatiotemporal information of dynamic environments. This mechanism would allow animals and humans to process complex time-changing situations neatly.
- MeSH
- chování zvířat MeSH
- krysa rodu Rattus MeSH
- potkani Long-Evans MeSH
- vnímání prostoru * fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chemogenetics is a newly developed set of tools that allow for selective manipulation of cell activity. They consist of a receptor mutated irresponsive to endogenous ligands and a synthetic ligand that does not interact with the wild-type receptors. Many different types of these receptors and their respective ligands for inhibiting or excitating neuronal subpopulations were designed in the past few decades. It has been mainly the G-protein coupled receptors (GPCRs) selectively responding to clozapine-N-oxide (CNO), namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), that have been employed in research. Chemogenetics offers great possibilities since the activity of the receptors is reversible, inducible on demand by the ligand, and non-invasive. Also, specific groups or types of neurons can be selectively manipulated thanks to the delivery by viral vectors. The effect of the chemogenetic receptors on neurons lasts longer, and even chronic activation can be achieved. That can be useful for behavioral testing. The great advantage of chemogenetic tools is especially apparent in research on brain diseases since they can manipulate whole neuronal circuits and connections between different brain areas. Many psychiatric or other brain diseases revolve around the dysfunction of specific brain networks. Therefore, chemogenetics presents a powerful tool for investigating the underlying mechanisms causing the disease and revealing the link between the circuit dysfunction and the behavioral or cognitive symptoms observed in patients. It could also contribute to the development of more effective treatments.
- MeSH
- duševní poruchy * genetika metabolismus MeSH
- klozapin analogy a deriváty farmakologie terapeutické užití MeSH
- lidé MeSH
- neurony metabolismus účinky léků MeSH
- nové syntetické drogy farmakologie MeSH
- receptory spřažené s G-proteiny metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- klozapin MeSH
- nové syntetické drogy MeSH
- receptory spřažené s G-proteiny MeSH
Animals can organize their behavior with respect to other moving animals or objects; when hunting or escaping a predator, when migrating in groups or during various social interactions. In rats, we aimed to characterize spatial behaviors relative to moving objects and to explore the cognitive mechanisms controlling these behaviors. Three groups of animals were trained to avoid a mild foot-shock delivered in one of three positions: either in front, on the left side, or on the right side of a moving robot. We showed the rats can recognize and avoid these specific areas. The avoidance behavior specific for the left or right side of the robot demonstrated animals not only react to "simple" stimuli such as increasing noise level or growing retinal image of an approaching object, but they process their spatial position relative to the object. Using an all-white robot without prominent visual patterns that would distinguish its different sides, we showed that the behavior does not depend on responses to prominent visual patterns, but that the rats can guide their navigation according to geometrical spatial relationship relative to the moving object. Rats' competence for navigation in space defined by a moving object resembles navigation abilities in stationary space. Recording of hippocampal single unit activity during rat's interaction with the robot proved feasibility of the task to uncover neuronal mechanism of this type of navigation.
- Klíčová slova
- dynamic environment, hippocampus, moving object, navigation, place cells, robot,
- Publikační typ
- časopisecké články MeSH
The role of NMDA receptors in learning, memory and hippocampal function has long been recognized. Post-mortem studies have indicated that the expression or subunit composition of the NMDA glutamate receptor subtype might be related to the impaired cognitive functions found in schizophrenia patients. NMDA receptor antagonists have been used to develop animal models of this disorder. There is accumulating evidence showing that not only the acute but also the chronic application of NMDA receptor antagonists may induce schizophrenia-like alterations in behavior and brain functions. However, limited evidence is available regarding the consequences of NMDA receptor blockage during periods of adolescence and early adulthood. This study tested the hypothesis that a 2-week treatment of male Long-Evans and Wistar rats with dizocilpine (MK-801; 0.5 mg/kg daily) starting at postnatal days (PD) 30 and 60 would cause a long-term cognitive deficit and changes in the levels of NMDA receptor subunits. The working memory version of the Morris water maze (MWM) and active place avoidance with reversal on a rotating arena (Carousel) requiring cognitive coordination and flexibility probed cognitive functions and an elevated-plus maze (EPM) was used to measure anxiety-like behavior. The western blot method was used to determine changes in NMDA receptor subunit levels in the hippocampus. Our results showed no significant changes in behaviors in Wistar rats. Slightly elevated anxiety-like behavior was observed in the EPM in Long-Evans rats with the onset of treatment on PD 30. Furthermore, Long-Evans rats treated from PD 60 displayed impaired working memory in the MWM. There were; however, no significant changes in the levels of NMDA receptor subunits because of MK-801 administration. These findings suggest that a 2-week treatment starting on PD 60 in Long-Evans rats leads to long-term changes in working memory, but this deficit is not paralleled by changes in NMDA receptor subunits. These results support the face validity, but not construct validity of this model. We suggest that chronic treatment of adolescent and adult rats does not constitute a plausible animal model of schizophrenia.
- Klíčová slova
- animal model, behavior, chronic treatment, dizocilpine, rats, schizophrenia, western blot,
- Publikační typ
- časopisecké články MeSH