Formation and consolidation of memories for highly stressful (traumatic) events is a complex process that involves interplay between multiple memory systems and has implications for etiology and treatment of stress- and trauma-related disorders. Here we study effects of sleep/wake states and high intra-hippocampal corticosterone on consolidation of aversive contextual memories, as well as consolidation of association between auditory unpaired phasic background cues and fear response in rats. Animals were implanted with EEG and EMG electrodes for sleep assessment and cannulas for intra-hippocampal corticosterone application. They were familiarized to a "safe box" and then trained in a fear conditioning paradigm in a distinct "shock box" with a prominent unpaired phasic background auditory cue. Immediately after conditioning, animals received bilateral intra-hippocampal saline (1 μl) or corticosterone (10 ng in 1 μl) injection and were either allowed to sleep or were kept awake for a following two-hour consolidation period. Memory tests 24 h later revealed that the saline-injected animals that slept during consolidation had significantly stronger fear responses in the shock box compared to the safe box as well as increased fear response in response to the auditory cue. Lack of sleep during the consolidation period in saline injected animals led to generalization of the fear response to the safe context, while association between auditory cue and fear response was preserved. High intra-hippocampal corticosterone levels during memory consolidation led to generalization of fear response to the safe context, regardless of sleep/wake state, while enhancement of response to auditory cue was not observed. Our results show how manipulation of conditions during consolidation can lead to greatly variable memories for an aversive episode with distinct behavioral outcomes. Observed overgeneralization of fear to safe context and altered fear response to background phasic cue has implications for understanding etiology of pathological memory alternations in stress-related conditions e.g., in posttraumatic stress disorder in humans.

• Klíčová slova
• Corticosterone, Fear conditioning, Hippocampus, Memory consolidation, Sleep,
• MeSH
• hipokampus fyziologie   MeSH
• kortikosteron * farmakologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• paměť * fyziologie   MeSH
• spánek fyziologie   MeSH
• strach fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kortikosteron * MeSH

Neural components enabling flexible cognition and behavior are well-established, and depend mostly on proper intercommunication within the prefrontal cortex (PFC) and striatum. However, dense projections from the ventral hippocampus (vHPC) alter the functioning of the medial PFC (mPFC). Dysfunctional hippocampo-prefrontal connectivity negatively affects the integrity of flexible cognition, especially in patients with schizophrenia. In this study, we aimed to test the role of the vHPC and mPFC in a place avoidance task on a rotating arena using two spatial flexibility task variants - reversal learning and set-shifting. To achieve this, we inactivated each of these structures in adult male Long-Evans rats by performing bilateral local muscimol (a GABAA receptor agonist) injections. A significantly disrupted performance was observed in reversal learning in the vHPC-inactivated, but not in the mPFC-inactivated rats. These results confirm the notion that the vHPC participates in some forms of behavioral flexibility, especially when spatial cues are needed. It seems, rather unexpectedly, that the mPFC is not taxed in these flexibility tasks on a rotating arena.

• Klíčová slova
• Behavioral flexibility, Carousel, Muscimol, Prefrontal cortex, Rotating arena, Ventral hippocampus,
• MeSH
• agonisté receptorů GABA-A farmakologie   MeSH
• hipokampus účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• muscimol farmakologie   MeSH
• pozornost účinky léků   fyziologie   MeSH
• prefrontální mozková kůra účinky léků   fyziologie   MeSH
• prostorové vidění účinky léků   fyziologie   MeSH
• reverzní učení účinky léků   fyziologie   MeSH
• učení vyhýbat se 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
• Názvy látek
• agonisté receptorů GABA-A MeSH
• muscimol MeSH

Memory is related to the function of N-methyl-D-aspartate (NMDA) receptors. Depending on the dose, NMDA receptor antagonists (such as memantine or MK-801) can impair memory and/or cognitive as well as procedural functions, while they also can prevent the long-term toxic effects of over-excitation of these receptors in pathophysiological processes. There is an unresolved question of whether memantine at low doses could exert an acute pro-cognitive activity. A therapeutic dose of memantine was found to improve short-term spatial memory tested in the alternation version of active place avoidance in a Carousel Maze, whereas no data are available on long-term memory in various versions of place avoidance. In an effort to reconcile this issue, rats were administered memantine (5 mg/kg) 30 min before a training session and trained in two different versions of place avoidance. A control group received saline injections. In an active place avoidance task (hereby referred to as Room+Arena-), this place was fixed to distal room cues, whereas cues from the arena were misleading. Performance thus demanded the on-going segregation of information that engages cognitive coordination. Following the Room+Arena- training, rats were trained in another place avoidance task (hereby referred to as Arena+), which requires focusing on substratal and idiothetic cues from the arena. In this version, a to-be-avoided sector rotated along with the arena in darkness that hid the extramaze cues. The rats given memantine avoided better than the control rats in the Room+Arena- task. In the Arena+ task, both groups had problems with acquiring the task. Subsequently, memantine was withdrawn and both groups relearned Room+Arena- avoidance with a new sector position. In this task, no effect of groups was seen. In conclusion, memantine at a therapeutic dose improved performance in a task that required the segregation of spatial stimuli into coherent subsets.

• Klíčová slova
• Carousel maze, Cognitive coordination, Memantine, Rats, Spatial place avoidance,
• MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• memantin farmakologie   MeSH
• podněty MeSH
• potkani Wistar MeSH
• prostorová paměť účinky léků   MeSH
• receptory N-methyl-D-aspartátu antagonisté a inhibitory   MeSH
• učení vyhýbat se účinky léků   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
• antagonisté excitačních aminokyselin MeSH
• memantin MeSH
• receptory N-methyl-D-aspartátu MeSH

The role of rodent hippocampus has been intensively studied in different cognitive tasks. However, its role in discrimination of objects remains controversial due to conflicting findings. We tested whether the number and type of features available for the identification of objects might affect the strategy (hippocampal-independent vs. hippocampal-dependent) that rats adopt to solve object discrimination tasks. We trained rats to discriminate 2D visual objects presented on a computer screen. The objects were defined either by their shape only or by multiple-features (a combination of filling pattern and brightness in addition to the shape). Our data showed that objects displayed as simple geometric shapes are not discriminated by trained rats after their hippocampi had been bilaterally inactivated by the GABAA-agonist muscimol. On the other hand, objects containing a specific combination of non-geometric features in addition to the shape are discriminated even without the hippocampus. Our results suggest that the involvement of the hippocampus in visual object discrimination depends on the abundance of object's features.

• Klíčová slova
• Hippocampus, Muscimol, Object discrimination, Operant conditioning, Visual discrimination,
• MeSH
• agonisté receptorů GABA-A farmakologie   MeSH
• chování zvířat účinky léků   fyziologie   MeSH
• diskriminační učení účinky léků   fyziologie   MeSH
• generalizace (psychologie) účinky léků   fyziologie   MeSH
• hipokampus účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• muscimol farmakologie   MeSH
• operantní podmiňování účinky léků   fyziologie   MeSH
• potkani Long-Evans MeSH
• rozpoznávání obrazu účinky léků   fyziologie   MeSH
• vnímání tvaru 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
• Názvy látek
• agonisté receptorů GABA-A MeSH
• muscimol MeSH

Adult neurogenesis in the dentate gyrus adds a substantial number of new functional neurons to the hippocampus network in rodents. To date, however, the function of these new granule cells remains unclear. We conducted an experiment to assess the contribution of adult neurogenesis in the dentate gyrus to acquisition and reversal learning in a task that predominantly requires generalization of a rule. Young adult male Long-Evans rats were repeatedly administered either a cytostatic temozolomide or saline for a period of four weeks (3 injections per week). Post treatment, animals were injected with bromodeoxyuridine to quantify adult neurogenesis in the dentate gyrus. For behavioral assessment we used hippocampus-dependent active place avoidance with reversal in a Carousel maze. Animals first learned to avoid a 60° sector on the rotating arena. Afterwards, sector was relocated to the opposite side of the rotating arena (reversal). The administration of temozolomide significantly improved the reversal performance compared to saline-treated rats. Our results suggest a significant, level-dependent, improvement of reversal learning in animals with reduced adult neurogenesis in hippocampus.

• Klíčová slova
• Active avoidance, Adult neurogenesis, Discrimination, Generalization, Hippocampus, Reversal,
• MeSH
• alkylační protinádorové látky farmakologie   MeSH
• dakarbazin analogy a deriváty   farmakologie   MeSH
• gyrus dentatus účinky léků   MeSH
• krysa rodu Rattus MeSH
• neurogeneze účinky léků   MeSH
• neurony účinky léků   MeSH
• potkani Long-Evans MeSH
• prostorové učení účinky léků   MeSH
• reverzní učení účinky léků   MeSH
• temozolomid MeSH
• učení vyhýbat se účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• dakarbazin MeSH
• temozolomid MeSH

Both humans and laboratory animals suffering from cerebellar lesions exhibit cognitive as well as many emotional and behavioral abnormalities. These latter have been already observed in the cerebellar mutant mice currently used to highlight some aspect of autism spectrum disorders. The aim of this study was to investigate the influence of cerebellar-related stress response abnormalities on spatial learning and memory. Cerebellar-deficient Lurcher mutant mice were exposed to water environment without active escape possibility and then tested for spatial learning in the Morris water maze. As a marker of stress intensity we measured corticosterone in urine. Finally, the volumes of individual components of the adrenal gland were estimated. Though having spatial navigation deficit in the water maze, Lurcher mice preserved a substantial residuum of learning capacity. Lurcher mutants had a higher increase of corticosterone level after exposure to the water environment than wild type mice. We did not observe any decrease of this physiological stress marker between the start and the end of the spatial navigation task, despite significant improvement of behavioral performances. Furthermore, zona fasciculata and zona reticularis of the adrenal cortex as well as the adrenal medulla were larger in Lurcher mice, reflecting high stress reactivity. We conclude that for both genotypes water exposure was a strong stressor and that there was no habituation to the experiment independently to the increasing controllability of the stressor (e.g. ability to find the escape platform). Based on these findings, we suggest that the enhanced stress response to water exposure is not the main factor explaining the spatial deficits in these cerebellar mutant mice.

• Klíčová slova
• Autism spectrum disorders, Cerebellum, Corticosterone, Lurcher, Morris water maze, Stress,
• MeSH
• fyziologický stres fyziologie   MeSH
• kortikosteron moč   MeSH
• myši - mutanty neurologické MeSH
• myši MeSH
• nadledviny patologie   MeSH
• prostorová navigace fyziologie   MeSH
• velikost orgánu fyziologie   MeSH
• vnímání prostoru fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kortikosteron MeSH

Although animals often learn and monitor the spatial properties of relevant moving objects such as conspecifics and predators to properly organize their own spatial behavior, the underlying brain substrate has received little attention and hence remains elusive. Because the anterior cingulate cortex (ACC) participates in conflict monitoring and effort-based decision making, and ACC neurons respond to objects in the environment, it may also play a role in the monitoring of moving cues and exerting the appropriate spatial response. We used a robot avoidance task in which a rat had to maintain at least a 25cm distance from a small programmable robot to avoid a foot shock. In successive sessions, we trained ten Long Evans male rats to avoid a fast-moving robot (4cm/s), a stationary robot, and a slow-moving robot (1cm/s). In each condition, the ACC was transiently inactivated by bilateral injections of muscimol in the penultimate session and a control saline injection was given in the last session. Compared to the corresponding saline session, ACC-inactivated rats received more shocks when tested in the fast-moving condition, but not in the stationary or slow robot conditions. Furthermore, ACC-inactivated rats less frequently responded to an approaching robot with appropriate escape responses although their response to shock stimuli remained preserved. Since we observed no effect on slow or stationary robot avoidance, we conclude that the ACC may exert cognitive efforts for monitoring dynamic updating of the position of an object, a role complementary to the dorsal hippocampus.

• Klíčová slova
• Avoidance, Enemy avoidance, Moving goal, Navigation, Rat, Robot,
• MeSH
• agonisté receptorů GABA-A farmakologie   MeSH
• cingulární gyrus účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• muscimol farmakologie   MeSH
• neurony účinky léků   fyziologie   MeSH
• podněty MeSH
• potkani Long-Evans MeSH
• pozornost účinky léků   fyziologie   MeSH
• prostorové chování účinky léků   fyziologie   MeSH
• reakční čas fyziologie   MeSH
• učení vyhýbat se účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté receptorů GABA-A MeSH
• muscimol MeSH

The processes that organize different thoughts and memories, allowing the separation of currently relevant and irrelevant information, are collectively known as cognitive control. The neuronal mechanisms of these processes can be investigated by place cell ensemble recordings during behaviors and environmental manipulations that present cognitive control challenges to selectively represent one of multiple possible alternative estimates of location. We review place cell studies that investigate responses to manipulations that dissociate the environment into two or more spatial frames of locations, often times to test notions of pattern separation. Manipulations, such as continuously rotating the recording chamber reveal that the ensemble discharge in hippocampus self-organizes into multiple, transiently-organized representations of space, each defined by the subset of coactive cells. Ensemble discharge in the hippocampus alternates between separate representations of frame-specific positions on timescales from 25 ms to several seconds. The dynamic, functional grouping of discharge into transiently co-active subsets of cells is predicted by the animal's changing behavioral needs. In addition to identifying neural correlates of cognitive control in hippocampus, these observations demonstrate that the separation of neuronal activity into distinctive representations depends on ongoing cognitive demands and that what can appear as noise, deviations from receptive field tuning, can substantially be the result of these internal knowledge-guided fluctuations. These findings inspire a new perspective that should be taken into account when investigating pattern separation--a perspective that emphasizes changes in hippocampal neural discharge that are happening on a short timescale and does not assume that patterns of neural discharge are steady and stationary across the several minutes of the recordings.

• Klíčová slova
• Cognitive control, Dynamic functional grouping, Hippocampus, Multiple representations, Overdispersion,
• MeSH
• buňky místa fyziologie   MeSH
• hipokampus fyziologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely neurologické * MeSH
• prostorová paměť fyziologie   MeSH
• prostorové učení fyziologie   MeSH
• vnímání prostoru fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Nogo-A protein is an important inhibitor of axonal growth, which also regulates neuronal plasticity in the CNS. Mutations in the gene encoding Nogo-A or abnormalities in Nogo-A expression are linked to neuropsychiatric disorders such as schizophrenia. The present study assesses the impact of constitutively reduced expression of Nogo-A on place navigation in a novel transgenic rat model. Two spatial paradigms were used: (1) A battery of tests in the Carousel maze requiring continuous processing of spatial information with increasing demands for the segregation of reference frames and behavioral flexibility and (2) a delayed-matching-to-place version of the Morris water maze (MWM), which requires place navigation and is sensitive to deficits in one-trial-encoded place representation. The Carousel maze testing revealed a subtle but significant impairment in management of reference frames. Matching-to-place learning in the Morris water maze was unaffected, suggesting an intact representation of an unmarked goal. Our results show that Nogo-A deficiency leads to cognitive deficit in processing of the reference frames. Such a deficit may be the result of neuro-developmental alterations resulting from Nogo-A deficiency.

• Klíčová slova
• Cognitive coordination, Nogo-A, Spatial mazes, Spatial navigation, Transgenic rat model,
• MeSH
• bludiště - učení fyziologie   MeSH
• down regulace * MeSH
• genový knockdown MeSH
• krysa rodu Rattus MeSH
• myelinové proteiny genetika   metabolismus   MeSH
• Nogo proteiny MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• prostorové chování fyziologie   MeSH
• učení vyhýbat se fyziologie   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
• myelinové proteiny MeSH
• Nogo proteiny MeSH
• Rtn4 protein, rat MeSH Prohlížeč

Bielavska and colleagues (Bielavska, Sacchetti, Baldi, & Tassoni, 1999) have recently shown that KN-62, an inhibitor of calcium/calmodulin-dependent kinase II (CaCMK), induces conditioned taste aversion (CTA) when introduced into the parabrachial nucleus (PBN) of rats. The aim of the present report was to assess whether activity of CaCMK in the PBN is changed during CTA. We induced CTA in one group of rats by pairing saccharin consumption with an ip injection of lithium chloride. Another group of rats received lithium alone (without being paired with saccharin consumption) to test whether lithium has an effect on CaCMK in the PBN, independent of those effects due to training. In animals receiving CTA training, CaCMK activity in extracts of PBN was reduced by approximately 30% at the postacquisition intervals of 12, 24, and 48 h, compared to control animals receiving saccharin with saline injection. By 120 h after CTA training, no effect on CaCMK was present. At those postacquisition intervals showing CaCMK activity effects due to CTA, there were no effects attributable to lithium alone. Lithium alone produced only a short-lasting reduction in CaCMK activity (at 20 min a 30% decrease, at 60 min a 23% decrease; and at 6, 12, and 24 h no decrease). The time course of lithium-induced effects differed markedly from that of CTA training. All changes were Ca2+/- -dependent; we did not observe any changes in Ca-independent activity. CTA effects on CaCMK were selective for PBN, insofar as we did not observe any CTA effects on CaCMK in the visual cortex, a brain region unrelated to taste pathways. Since CTA produces a relatively long-lasting reduction in CaCMK activity (lasting 2 days or more) specifically in the PBN, which is critical a relay for taste information, the reduction of CaCMK activity may enable the consolidation of taste memory in an aversive situation.

• MeSH
• chuť fyziologie   MeSH
• krysa rodu Rattus MeSH
• plexus brachialis metabolismus   MeSH
• podmiňování (psychologie) fyziologie   MeSH
• potkani Long-Evans MeSH
• proteinkinasy závislé na vápníku a kalmodulinu metabolismus   MeSH
• vápník metabolismus   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
• proteinkinasy závislé na vápníku a kalmodulinu MeSH
• vápník MeSH