RESUMEN
The conditioned cue preference paradigm was used to study how rats use extra-maze cues to discriminate between 2 adjacent arms on an 8-arm radial maze, a situation in which most of the same cues can be seen from both arms but only one arm contains food. Since the food-restricted rats eat while passively confined on the food-paired arm no responses are reinforced, so the discrimination is due to Pavlovian stimulus-reward (or outcome) learning. Consistent with other evidence that rats must move around in an environment to acquire a spatial map, we found that learning the adjacent arms CCP (ACCP) required a minimum amount of active exploration of the maze with no reinforcers present prior to passive pairing of the extra-maze cues with the food reinforcer, an instance of latent learning. Temporary inactivation of the hippocampus during the pre-exposure sessions had no effect on ACCP learning, confirming other evidence that the hippocampus is not involved in latent learning. A series of experiments indentified a circuit involving fimbria-fornix and dorsal entorhinal cortex as the neural basis of latent learning in this situation. In contrast, temporary inactivation of the entorhinal cortex or hippocampus during passive training or during testing blocked ACCP learning and expression, respectively, suggesting that these two structures co-operate in using spatial information to learn the location of food on the maze during passive pairing and to express this combined information during testing. In parallel with these processes we found that the amygdala processes information leading to an equal tendency to enter both adjacent arms (even though only one was paired with food) suggesting that the stimulus information available to this structure is not sufficiently precise to discriminate between the ambiguous cues visible from the adjacent arms. Expression of the ACCP in normal rats depends on hippocampus-based learning to avoid the unpaired arm which competes with the amygdala-based tendency to enter that arm. In contrast, there is cooperation between amygdala- and hippocampus-based tendencies to enter the food-paired arm. These independent forms of learning contribute to the rat's ability to discriminate among spatial locations using ambiguous extra-maze cues.
Asunto(s)
Amígdala del Cerebelo/fisiología , Corteza Entorrinal/fisiología , Hipocampo/fisiología , Memoria/fisiología , Animales , Condicionamiento Psicológico/fisiología , Señales (Psicología) , Aprendizaje Discriminativo/fisiología , Aprendizaje por Laberinto/fisiología , Ratas , Refuerzo en Psicología , Recompensa , Biología de SistemasRESUMEN
We investigated whether systems consolidation of spatial memory could be detected in a non-navigational, spatial-learning test that takes advantage of rats' natural propensity to preferentially investigate an object that was displaced relative to spatial cues more than an object that remained stationary. Previous studies using navigational spatial-learning tests have generally failed to reveal temporally-graded retrograde amnesia, possibly because the hippocampus needs to be intact for the retrieval and/or processing of navigational information during the test. In the present study, the hippocampus of rats was kept inactivated, at two sites along its septo-temporal axis (dorsal and intermediate), for four consecutive days, beginning either 3h or 5 days after familiarization to two identical objects in an open field. Rats that had their hippocampus inactivated beginning 5 days but not 3h after familiarization showed evidence that they remembered the previous location of the displaced object. The results suggest that systems consolidation of spatial memories can be detected using a non-navigational test of spatial memory.
Asunto(s)
Amnesia Retrógrada/fisiopatología , Hipocampo/fisiopatología , Aprendizaje por Laberinto/fisiología , Refuerzo en Psicología , Retención en Psicología , Animales , Masculino , Ratas , Ratas Long-Evans , Retención en Psicología/fisiología , Percepción Espacial/fisiologíaRESUMEN
In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.
Asunto(s)
Hipocampo/fisiología , Memoria/fisiología , Análisis de Varianza , Animales , Conducta Animal/fisiología , Conducta Exploratoria/fisiología , Hipocampo/lesiones , Hipocampo/patología , Masculino , Distribución Aleatoria , Ratas , Ratas Long-Evans , Factores de TiempoRESUMEN
We investigated whether object familiarization was related to novel-object preference in the novel-object preference (NOP) test in rats. In Experiment 1, we found that no significant correlation existed between the time spent investigating 2 identical copies of a sample object and the degree of preference for a novel object. In Experiment 2, rats investigated 2 identical sample objects for a total of 5, 30, 60, 90 or 120s. Investigatory preference for the novel object was compared to chance expectancy as well as between the groups. Only the 90-s group and the 120-s group displayed above-chance investigatory preference for the novel object, but novel-object preference for these 2 groups did not differ from each other, suggesting that a minimal amount of sample object investigation is necessary for rats to develop a novel-object preference, beyond which no increase in novel-object preference was found. In Experiments 3 and 4, normal rats and rats with hippocampal lesions were given repeated test trials, with the same sample object presented with a different novel object, at 24-h and (Experiment 3) and 35-s intervals (Experiment 4). In both experiments, novel-object preference did not increase in magnitude with repeated sample object exposures, suggesting that increased familiarity with the sample object does not result in increased novel-object preference. Rats with lesions of the dorsal hippocampus showed an unreliable investigatory preference for the novel object. These results are discussed in terms of the potential limitations of the NOP test as a tool for the assessment of object-recognition memory in rats.
Asunto(s)
Conducta de Elección , Conducta Exploratoria , Animales , Conducta Animal , Habituación Psicofisiológica , Hipocampo/fisiología , Masculino , Memoria , Ratas , Ratas Long-Evans , Reconocimiento en Psicología , Conducta SocialRESUMEN
We tested the effects of temporary inactivation of the dorsal entorhinal cortex on spatial discrimination using a conditioned cue preference (CCP) paradigm. The three phases of the procedure were: pre-exposure: unreinforced exploration of the center platform and two adjacent arms of an eight-arm radial maze; training: rats were confined to the ends of the two arms on alternate days - one arm always contained food and the other never contained food; testing: unreinforced exploration of the center platform and the two arms. Rats that received bilateral infusions of saline into the dorsal entorhinal cortex before the training trials or before the test trial spent significantly more time in the arm that previously contained food than in the arm that never contained food, demonstrating that they had acquired and were able to express information that discriminated between the two adjacent maze arms. In contrast, rats that received bilateral, intra-entorhinal infusions of muscimol, a gamma-aminobutyric acid(a) (GABA(a)) agonist, before either training or testing spent equal amounts of time in the two arms, indicating that they failed to acquire and were unable to express this information. Interactions between the entorhinal cortex and hippocampus in the acquisition and expression of the information required for this discrimination are discussed.
Asunto(s)
Corteza Entorrinal/fisiología , Aprendizaje por Laberinto/fisiología , Recuerdo Mental/fisiología , Percepción Espacial/fisiología , Animales , Corteza Entorrinal/efectos de los fármacos , Agonistas del GABA/farmacología , Agonistas de Receptores de GABA-A , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Muscimol/farmacología , Pruebas Neuropsicológicas , Ratas , Ratas Long-Evans , Receptores de GABA-A/metabolismo , Percepción Espacial/efectos de los fármacos , Factores de TiempoRESUMEN
We investigated whether the ventral and dorsal hippocampus were differentially involved in incidental spatial learning. Rats with ventral and dorsal hippocampal lesions were tested on an unreinforced test of spatial memory that takes advantage of their natural propensity to explore novelty. Rats were presented with two copies of an identical object in a large circular open field arena. Subsequently, the rats were placed back into the open field with one of the objects displaced to an adjacent quadrant of the arena. Sham-operated rats and rats with ventral hippocampal lesions spent more time in the quadrant that contained the displaced object than in the quadrant that contained the non-displaced object, and more time investigating the displaced object than the non-displaced object. Rats with dorsal hippocampal lesions were impaired on both measures. Both sham and ventral hippocampal lesioned rats subsequently learned to retrieve a food pellet in the ends of each arm of a radial maze. Rats with lesions to the dorsal hippocampus showed no significant improvement in the number of errors made across training sessions and made significantly more errors, overall, than rats with ventral hippocampal or sham lesions. The findings suggest that an intact dorsal but not ventral hippocampus is necessary for spatial learning in rats.
Asunto(s)
Hipocampo/fisiología , Aprendizaje/fisiología , Percepción Espacial/fisiología , Análisis de Varianza , Animales , Conducta Exploratoria/fisiología , Hipocampo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , N-Metilaspartato/toxicidad , Neurotoxinas/toxicidad , Ratas , Ratas Long-Evans , Conducta Espacial/fisiología , Factores de TiempoRESUMEN
A non-navigational test of incidental spatial learning was used to determine whether hippocampal damage causes temporally-graded retrograde amnesia (TGRA) for allocentric-spatial information. Rats were exposed to two identical objects in a circular open field for 7 min on seven consecutive days. In the 1-3 days after the last day of familiarization, rats received neurotoxic lesions of the hippocampal formation (HPC) or sham lesions. Another two groups received the same lesions 3 weeks after familiarization. The rats were then placed back in the open field with one object displaced, and the time spent in each of the quadrants as well as time spent exploring the objects was recorded. Rats that received HPC lesions 3 weeks but not 1-3 days after familiarization showed evidence of preserved remote spatial memory; however, their remote memory was expressed through different behavior than control rats. Rats with HPC lesions spent more time with the displaced object than with the object that remained in the same place, whereas control rats spent more time in the quadrant where the displaced object used to be. These results suggest that remote spatial memories may be preserved with a sufficiently long familiarization-to-surgery interval before HPC lesions, but that the nature of these memories may differ in quantity and/or quality from those of intact rats.
Asunto(s)
Amnesia/fisiopatología , Hipocampo/fisiopatología , Aprendizaje/fisiología , Percepción Espacial/fisiología , Análisis de Varianza , Animales , Conducta Exploratoria/fisiología , Habituación Psicofisiológica , Hipocampo/efectos de los fármacos , Masculino , Memoria/fisiología , N-Metilaspartato/toxicidad , Neurotoxinas/toxicidad , Ratas , Ratas Long-Evans , Factores de TiempoRESUMEN
Recent evidence suggests that rats require an intact hippocampus in order to recognize familiar objects when they encounter them again in a different context. The two experiments reported here further examined how changes in context affect rats' performance on the novel-object preference (NOP) test of object-recognition memory, and how those effects interact with the effects of HPC damage. Rats with HPC lesions and control rats received NOP testing in either the same context in which they had previously encountered sample objects, or in a different but equally familiar context. In Experiment 1, the two contexts had very few overlapping cues within or outside the apparatus; thus, the differences between them were global. Consistent with previous results, control rats showed a novel-object preference in both the unchanged and (globally) changed contexts, whereas rats with HPC lesions displayed a preference only in the unchanged context. In Experiment 2, the context shift included only local features proximal to the test objects. The main results were the reverse of Experiment 1--rats with HPC lesions displayed a novel-object preference in both the unchanged and (locally) changed contexts, whereas control rats displayed a preference only in the unchanged context. The findings are consistent with the view that HPC damage does not cause a general inability to recognize objects, nor an inability to encode or store a representation of the context in which the objects are encountered. They suggest instead that HPC damage impairs the ability to remember specific locations of familiar objects within a particular context.
Asunto(s)
Señales (Psicología) , Hipocampo/fisiología , Memoria/fisiología , Reconocimiento en Psicología/fisiología , Animales , Masculino , Ratas , Ratas Long-EvansRESUMEN
The relationship of the entorhinal cortex (EC) and fimbria-fornix (FF) in unreinforced spatial (latent) learning was studied using the conditioned-cue-preference task on an eight-arm radial maze. The maze was turned before every trial to eliminate the use of local cues. During three pre-exposure sessions, food-deprived rats explored the center platform and two adjacent arms of the maze. Since most of the same cues were visible from both arm locations, discriminating them required spatial learning. The rats were then alternately confined to the end of each arm over several days: one arm always contained food, the other was empty. Finally, the rats were allowed free access to both arms with no food present. Normal rats spent more time in their food-paired than in their unpaired arms showing that they learned to discriminate between the arm locations. Bilateral micro-injections of muscimol into the dorsal, but not into the ventral EC, given before the pre-exposure sessions only, impaired the discrimination. The discrimination was also impaired in rats with unilateral lesions of FF and contralateral injections of muscimol into the dorsal EC given before the pre-exposure sessions. Ipsilateral FF lesions and entorhinal inactivation had no effect. These results indicate that the acquisition of information during unreinforced exploration of a novel environment requires an intact circuit involving the dorsal EC and fimbria fornix. Together with previous reports, that this form of learning does not require a functional hippocampus, (Gaskin et al. (2005) Hippocampus 15:1085-1093) the findings also suggest that the acquisition of certain kinds of unreinforced information by this circuit is independent of the hippocampus.
Asunto(s)
Corteza Entorrinal/fisiología , Fórnix/fisiología , Aprendizaje por Laberinto/fisiología , Vías Nerviosas/fisiología , Orientación/fisiología , Percepción Espacial/fisiología , Animales , Señales (Psicología) , Aprendizaje Discriminativo/efectos de los fármacos , Aprendizaje Discriminativo/fisiología , Corteza Entorrinal/anatomía & histología , Corteza Entorrinal/efectos de los fármacos , Fórnix/anatomía & histología , Fórnix/efectos de los fármacos , Agonistas del GABA/farmacología , Hipocampo/anatomía & histología , Hipocampo/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Muscimol/farmacología , Vías Nerviosas/efectos de los fármacos , Pruebas Neuropsicológicas , Orientación/efectos de los fármacos , Ratas , Ratas Long-Evans , Refuerzo en Psicología , Percepción Espacial/efectos de los fármacosRESUMEN
The conditioned cue preference (CCP) was used to study how rats discriminate between adjacent arms on a radial maze. Chai and White (Behav Neurosci 2004, 118:770-784) showed that an intact dorsal hippocampus is required to learn this discrimination and that an amygdala-based conditioned approach response that produces an equal tendency to enter both arms is simultaneously acquired. In the present experiments, rats were preexposed to the maze with no food and trained by alternately confining them at the ends of two adjacent arms, one that contained food and one that did not. When given a choice between these arms with no food present, the rats spent more time on their food-paired arms, suggesting they had learned to discriminate their locations. Temporary inactivation of the dorsal hippocampus with muscimol during confinement on the food-paired arm had no effect on the discrimination, but inactivation while on the no-food arm impaired it. This pattern of effects was reversed in rats with amygdala lesions (inactivation on the food-paired arm impaired, but inactivation on the no-food arm had no effect on the discrimination), showing that hippocampus-based and amygdala-based learning interact to influence the behavior of normal rats in this situation. The dorsal hippocampus learns about locations that contain food and about locations that do not contain food. The amygdala-based tendency to enter the food-paired arm cooperates with hippocampus-based foraging for food on the food-paired, but the amygdala-based tendency to enter the no-food arm competes with hippocampus-based learning about the absence of food on that arm.
Asunto(s)
Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Aprendizaje Discriminativo/fisiología , Hipocampo/citología , Hipocampo/fisiología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Desnervación , Aprendizaje Discriminativo/efectos de los fármacos , Alimentos , Agonistas del GABA/farmacología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Muscimol/farmacología , Vías Nerviosas , Ratas , Ratas Long-Evans , Percepción Espacial/efectos de los fármacos , Percepción Espacial/fisiologíaRESUMEN
Learning to discriminate between spatial locations defined by two adjacent arms of a radial maze in the conditioned cue preference paradigm requires two kinds of information: latent spatial learning when the rats explore the maze with no food available, and learning about food availability in two spatial locations when the rats are then confined in one arm with food and the other with no food. Previous research showed that a functional dorsal hippocampus is not required for latent learning. The present experiments show that it is required for learning about food availability, and during retrieval of both types of information.
Asunto(s)
Aprendizaje Discriminativo/fisiología , Hipocampo/fisiología , Aprendizaje por Laberinto/fisiología , Percepción Espacial/fisiología , Conducta Espacial/fisiología , Análisis de Varianza , Animales , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Aprendizaje Discriminativo/efectos de los fármacos , Agonistas del GABA/administración & dosificación , Hipocampo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Microinyecciones , Muscimol/administración & dosificación , Ratas , Refuerzo en Psicología , Percepción Espacial/efectos de los fármacos , Conducta Espacial/efectos de los fármacosRESUMEN
The conditioned cue preference (CCP) task was used to study the ability of rats to discriminate between spatial locations. Food-deprived rats explored an eight-arm radial maze with no food present (pre-exposure). On subsequent days, they were alternately confined in one arm of the maze with food and in another arm with no food (training), followed by a preference test with no food present, to determine if they had learned to discriminate between the two arm locations. No injections were given during the two latter phases. With adjacent radial maze arms, rats given three 10-min pre-exposure sessions and four food-pairing trials exhibited a preference for their food-paired arms; rats not pre-exposed did not exhibit this preference. Rats pre-exposed 30 min after dorsal hippocampus injections of muscimol exhibited the preference. With widely separated maze arms, rats given two training trials with no pre-exposure exhibited a preference for the food-paired arm; rats that were given one pre-exposure session did not. Rats pre-exposed 30 min after dorsal hippocampus injections of muscimol did not exhibit the preference. The same intrahippocampal muscimol injections that failed to affect the influence of pre-exposure on CCP learning with both arm configurations impaired win-shift performance, a standard test of spatial learning. These findings suggest that a functional dorsal hippocampus is not required for the (incidental or latent) learning that occurs during unreinforced exploration of a novel environment. The information acquired during this activity subsequently produces a latent learning effect if it is used to discriminate between two ambiguous locations (adjacent arms) or a latent inhibition--like effect if it is used to discriminate between two unambiguous locations (separated maze arms).
Asunto(s)
Conducta Exploratoria/fisiología , Hipocampo/fisiología , Aprendizaje/fisiología , Animales , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Señales (Psicología) , Discriminación en Psicología/fisiología , Corteza Entorrinal/fisiología , Agonistas del GABA/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/cirugía , Masculino , Aprendizaje por Laberinto/fisiología , Muscimol/farmacología , Ratas , Ratas Long-Evans , Análisis y Desempeño de Tareas , Factores de TiempoRESUMEN
Retrograde and anterograde object-recognition memory was assessed in rats with cytotoxic lesions of the hippocampal formation (HPC), using a paradigm based on the natural tendency of rats to spend more time exploring novel objects than familiar objects. The rats were allowed to explore a sample object for 5 min/day on 5 consecutive days, either 5 weeks or 1 week before surgery. After surgery, retrograde recognition was assessed by comparing the amount of time spent exploring the sample versus a novel object in a free-choice situation. Control rats spent more time exploring the novel object than the sample objects from both presurgery time periods, whereas rats with HPC lesions did not discriminate between the novel objects and sample objects from either presurgery time period. Despite their deficits on the retrograde recognition test, the rats with HPC lesions performed like control rats on anterograde recognition tests, displaying a strong exploratory preference for novel objects over sample objects, with retention delays of either 15 min or 24 h. The findings suggest that extrahippocampal circuitry is capable of supporting object recognition, but only if the HPC does not participate in encoding the original encounter with the object.
Asunto(s)
Amnesia Anterógrada/fisiopatología , Amnesia Retrógrada/fisiopatología , Hipocampo/fisiopatología , Vías Nerviosas/fisiopatología , Reconocimiento en Psicología/fisiología , Amnesia Anterógrada/patología , Amnesia Retrógrada/patología , Animales , Desnervación , Modelos Animales de Enfermedad , Hipocampo/lesiones , Hipocampo/patología , Masculino , Memoria/fisiología , Vías Nerviosas/lesiones , Vías Nerviosas/patología , Reconocimiento Visual de Modelos/fisiología , Ratas , Ratas Long-Evans , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
Rats have a natural tendency to spend more time exploring novel objects than familiar objects, and this preference can be used as an index of object recognition. Rats also show an exploratory preference for objects in locations where they have not previously encountered objects (an index of place memory) and for familiar objects in contexts different from those in which the objects were originally encountered (an index of context memory). In this experiment, rats with cytotoxic lesions of the hippocampal formation were tested on all three versions of the novelty-preference paradigm, with a 5-min retention interval between the familiarization and test phases. Rats with sham lesions displayed a novelty preference on all three trial types, whereas the rats with hippocampal lesions displayed a novelty preference on Object trials but did not discriminate between the objects on Place trials or Context trials. The findings indicate that hippocampal damage impairs memory for contextual or spatial aspects of an experience, whereas memory for objects that were part of the same experience are left relatively intact.