Parallel augmentation of hippocampal long-term potentiation, theta rhythm, and contextual fear conditioning in water-deprived rats.

The influence of water deprivation on hippocampal long-term potentiation (LTP), theta rhythm, and contextual fear conditioning in 56 adult male rats was examined. In Exp 1, hippocampal EEG activity and perforant path LTP were assessed in pentobarbital-anesthetized rats. Water deprivation did not affect baseline cell excitability or low-frequency synaptic transmission in the dentate gyrus, but it increased the magnitude of perforant path LTP and elevated the proportion of theta rhythm in the EEG. In Exp 2, rats were classically conditioned to fear a novel context through the use of aversive footshocks. Water deprivation facilitated the rate of contextual fear conditioning but did not alter the asymptote of learning. Exp 3 demonstrated that the facilitation of contextual fear conditioning was not due to a change in unconditional shock sensitivity. These results suggest that water deprivation exerts an influence on contextual fear conditioning by modulating hippocampal LTP and theta rhythm and that these processes serve to encode contextual information during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning of hippocampal theta patterns in the rat.

Electrical stimulation (88 Hz) of the lateral hypothalamus elicited a sustained theta response at hippocampal recording sites in 11 male Sprague-Dawley rats immobilized with succinylcholine. By pairing this UCS with a 10-sec presentation of a light, conditioned theta responses were demonstrated in as few as 40 trials. Spectral analysis of hippocampal bioelectric patterns during acquisition, extinction, and reconditioning indicated that the earliest change as a result of conditioning was a loss of power in EEG frequency below 8 Hz, followed by the development of a peak at 8 Hz with further conditioning. Extinction was associated with an increase in power of the frequencies below 8 Hz. When the conditioned Ss were tested in the absence of the neuromuscular blocking agent, the CS elicited a theta response that was associated with slow motor activity on 70% of the trials. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Partial hippocampal inactivation: Effects on spatial memory performance in aged and young rats.

Changes in anatomical or functional connectivity during normal aging are thought to contribute to cognitive alterations over the lifespan. Neural network theories predict that synaptic loss in an aging brain could place the organism near the point of dysfunction in the nonlinear curve defining neural compromise versus performance. The present experiments examined whether aged rats are closer to this point of behavioral dysfunction by reversibly inactivating one or both hippocampal hemispheres. As expected, bilateral tetracaine inactivation of the hippocampus disrupted spatial memory in both age groups. Unilateral left hippocampal inactivation significantly increased errors only in aged rats; however, unilateral inactivation of the right hippocampus had no effect. The present outcome could reflect more extensive synaptic dysfunction in the aged right hippocampus or a greater involvement of the left hippocampus in spatial working memory problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of low-intensity hippocampal stimulation on spatial versus working memory in rats.

Investigated differing predictions from the spatial mapping hypothesis of hippocampal function proposed by O'Keefe and Nadel (1978) and the working memory hypothesis proposed more recently by Olton and colleagues (Olton, Becker, & Handelmann, 1979). Each of 2 groups of rats was trained to use a different strategy to locate a submerged platform in opaque water. The MAP group used a spatial mapping strategy to reach a platform in a fixed location, whereas the CUE group used a guidance strategy, which involved following a cue that signaled the location of a randomly placed platform. Half of each group was given low-level unilateral electrical stimulation of the dentate gyrus and immediately tested on the water maze task. Results of Exp 1 show that both the MAP and CUE groups were impaired by stimulation. However, there was an inadvertent spatial element involved in the CUE task. When this element was eliminated in Exp 3, the same CUE Ss were unaffected by a 2nd series of stimulation trials, whereas the MAP Ss continued to show impairment. Results strongly support the cognitive mapping hypothesis and provide little support for the working memory hypothesis of hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of retroactive interference in the spatial memory of normal rats and rats with hippocampal lesions.

Studied the importance of retroactive interference (RI) in memory for spatial locations by using a 12-arm radial maze and a standard RI paradigm. 26 male albino Sprague-Dawley rats in the RI condition first learned to choose 4 of the 12 arms, followed by training to a 2nd set of 4 arms. In the control condition for interference, Ss learned the 1st set of arms but were not trained to approach the 2nd set. Thereafter, Ss in each interference condition were assigned to groups (hippocampal, cortical control, or unoperated control), the operations were carried out, and then all Ss were tested for retention of the set of arms learned first. Contrary to predictions of the cognitive map theory (J. O'Keefe and L. Nadel, 1978), RI was found in control Ss. The severe memory deficit found in hippocampals was not influenced by the interference variable. In addition to impaired performance early in relearning, Ss with hippocampal lesions continued to make many errors throughout the 10 wks of testing, including choices to unbaited arms and repeated entries into baited arms. However, hippocampals eventually learned not to reenter unbaited arms. Data indicate a deficit in the selection and utilization of sets of responses and are interpreted as implicating the hippocampus in retrieval processes. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ventral hippocampal ibotenic acid lesions block chronic nicotine-induced spatial working memory improvement in rats

Chronic nicotine infusions have been found to significantly improve working memory performance in the radial-arm maze. This effect is blocked by co-infusions of the nicotinic antagonist mecamylamine. Acute nicotine injections also improve working memory performance in the radial-arm maze. This effect is also blocked by mecamylamine co-administration. Recent local infusions studies have demonstrated the importance of the ventral hippocampus for nicotinic involvement in memory. Local infusions of mecamylamine, DHbetaE or MLA impair working memory performance on the radial-arm maze. The current study was conducted to determine the importance of the ventral hippocampus for the chronic effects of nicotine. Rats were trained on the working memory task in an eight-arm radial maze. After acquisition they underwent either infusions of ibotenic acid lesions or vehicle infusions and received subcutaneous implants of osmotic minipumps that delivered either nicotine at a dose of 5 mg kg-1 day-1 or vehicle in a 2x2 design. The rats then were given 2 days of recovery and were tested on the radial-arm maze three times per week for the next 4 weeks. As seen in previous studies, in the sham lesioned group nicotine infusions caused a significant improvement in choice accuracy. In contrast no nicotine-induced improvement was seen in the rats after ibotenic acid lesions of the ventral hippocampus. The effect of nicotine was blocked even though this lesion did not cause a deficit in performance. Previous work showed that chronic nicotine infusion still caused a significant improvement in working memory performance in the radial-arm maze after knife-cut lesions of the fimbria-fornix carrying the septo-hippocampal cholinergic innervation. Thus it appears that it is the postsynaptic nicotinic receptors in the ventral hippocampus which are critically important for the expression of the chronic nicotine induced working memory improvement.     

Little and often: Ingestive behavior patterns following hippocampal lesions in rats.

Lesions of both dorsal and ventral hippocampus were produced by multiple infusions of the excitotoxin AMPA. Meal patterns recorded before and after lesioning showed no change in total food intake, but a striking behavioral syndrome in which the lesioned rats took smaller meals 2–3 times as frequently and showed a similar change in drinking. In addition, lesioned rats alternated more frequently between feeding and drinking during a single bout of ingestive behavior. There were no group differences in the satiety sequence that followed a meal. In an open field test, lesioned rats showed enhanced locomotion in the periphery and reduced rearing. An olfactory habituation–dishabituation task showed that the lesioned rats investigated olfactory stimuli less but dishabituation to a changed stimulus was normal. The data are discussed in terms of changes in behavioral switching or a possible interoceptive agnosia following hippocampal damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Instrumental response persistence following induction of hippocampal theta frequency during fixed-ratio responding in rats.

Four groups of 6 male albino rats (24 Ss) were used to investigate the relationship between hippocampal theta and instrumental response persistence. All Ss were first trained on a discrete-trial FR-10 schedule of reinforcement. In Phase 2, hippocampal theta was induced via electrical stimulation of medial septal pacemaker cells through implanted electrodes at the beginning of 50% of the 8 daily FR-10 trials for experimental Ss, while stimulated-control Ss received 200-Hz medial septal stimulation which does not induce theta. The 2 remaining control groups continued as in the training phase. In Phase 3, FR-10 responding was extinguished in all Ss. Induction of hippocampal theta depressed responding and led to greater resistance to extinction in the experimental group compared with the other groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Object exploration and reactions to spatial and nonspatial changes in hooded rats following damage to parietal cortex or hippocampal formation.

Hooded rats with bilateral lesions of the anterior part of the hippocampal formation (HIP), anterior region of the posterior parietal cortex (APC), or posterior region of the posterior parietal cortex (PPC) were compared with controls for their exploration of 5 objects in an open field, habituation of locomotion and object investigation, and response to spatial and nonspatial change. First, all groups displayed habituation of both locomotor and exploratory activity. Second, controls selectively reexplored displaced objects, and APC-lesioned rats reexplored all objects, whereas PPC- and HIP-lesioned rats failed to react to the spatial change. Third, a novel object induced reexploration in all groups. Results are consistent with the roles of the HIP and PPC in spatial information processing. Moreover, the APC and PPC are involved in attentional effortful processing and visuospatial information processing necessary for spatial representation, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hippocampal and parietal cortex lesions on memory for egocentric distance and spatial location information in rats

To assess the working memory system for egocentric distance and place information, delayed matching-to-sample (DMTS) go/no-go tasks were run for each rat. To assess the reference memory system, and to serve as a control for nonmemory deficits, successive discrimination go/no-go tasks were then conducted using the same rats. Rats with hippocampal, but not parietal cortex, lesions were impaired relative to controls in the working memory (DMTS) task for both egocentric distance and place information, although the deficit observed in the working memory task for egocentric distance information by rats with hippocampal lesions was mild. Neither hippocampal nor parietal cortex lesioned rats were impaired relative to controls in the reference memory (successive discrimination) task for either cue. The hippocampus appears to be involved in working memory for egocentric distance and in spatial location information, whereas the parietal cortex is not.     

Remembrance of places you passed: Social spatial working memory in rats.

Pairs of rats were tested in a radial-arm maze to determine whether the spatial choices made by one rat affect the subsequent spatial choices of the other rat. In a free-choice procedure, rats showed an increased tendency to choose the location that had most recently been chosen by a foraging partner but a decreased tendency to visit locations that the foraging partner had visited earlier. Forced-choice procedures were used to better control the social stimulus and the interactions between the rats. Under some conditions, locations were chosen later in the choice sequence of a subject rat if another rat had been observed choosing that location. Odor and other physical traces of the other rat's visits were ruled out as explanations for this effect. The results demonstrate the existence of working memory for locations visited by a familiar conspecific. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychological stress impairs spatial working memory: Relevance to electrophysiological studies of hippocampal function.

Stress blocks hippocampal primed-burst potentiation, a low threshold form of long-term potentiation, thereby suggesting that stress should also impair hippocampal-dependent memory. Therefore, the effects of stress on working (hippocampal-dependent) and reference (hippocampal-independent) memory were evaluated. Rats foraged for food in seven arms of a 14-arm radial maze. After they ate the food in four of the seven baited arms, they were placed in an unfamiliar environment (stress) for a 4-hr delay. At the end of the delay they were returned to the maze to locate the food in the 3 remaining baited arms. Stress impaired only working memory. Stress interfered with the retrieval of previously stored information (retrograde amnesia), but did not produce anterograde amnesia. Stress appears to induce a transient disruption of hippocampal function, which is revealed behaviorally as retrograde amnesia and physiologically as a blockade of synaptic plasticity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of dorsal versus ventral hippocampal, total hippocampal, and parietal cortex lesions on memory for allocentric distance in rats.

To test for the contribution of the parietal cortex and hippocampus to memory for allocentric spatial cues, the authors trained rats on a go/no-go task that required the rat to remember the distance between two visual cues. Total hippocampal lesions impaired working-memory representation for allocentric distance, whereas parietal cortex lesions resulted in only a transient impairment. In a second experiment, neither hippocampal nor parietal cortex lesions impaired allocentric distance discrimination. A third experiment showed that both the dorsal and ventral areas of the hippocampal formation must be destroyed to impair working memory for allocentric distance information. There appears to be a dissociation between the hippocampus and parietal cortex in mediating memory for allocentric distance information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial septal lesions disrupt spatial, but not nonspatial, working memory in rats.

In Exp 1, rats with small medial septal lesions were less able than were control rats to remember the location of the arm of a Y maze they had been forced to enter on the preceding sample run. Moreover, as the retention interval between the sample and choice runs on this spatial delayed nonmatching-to-sample (DNMTS) task was increased to 1 and 2 min, the magnitude of the deficit increased. In contrast, these same lesioned rats were not deficient in Exp 2 in their ability to remember the object they had encountered in the straight alley on the sample run. In fact, when the retention interval was increased to 1 min on this nonspatial DNMTS task, the rats with medial septal lesions were more accurate than were the controls. This pattern of results did not appear to be due to task difficulty, recovery of function, or sequence of training. Rather, these results indicate that damage to the septohippocampal system disrupts spatial working memory more than it disrupts nonspatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nutritional deficits during early development affect hippocampal structure and spatial memory later in life.

Development rates vary among individuals, often as a result of direct competition for food. Survival of young might depend on their learning abilities, but it remains unclear whether learning abilities are affected by nutrition during development. The authors demonstrated that compared with controls, 1-year-old Western scrub jays (Aphelocoma californica) that experienced nutritional deficits during early posthatching development had smaller hippocampi with fewer neurons and performed worse in a cache recovery task and in a spatial version of an associative learning task. In contrast, performance of nutritionally deprived birds was similar to that of controls in 2 color versions of an associative learning task. These findings suggest that nutritional deficits during early development have long-term consequences for hippocampal structure and spatial memory, which, in turn, are likely to have a strong impact on animals' future fitness (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of ventral subicular and hippocampal neuron spatial firing patterns in complex and simplified environments.

Activity from ventral subicular and hippocampal CA1 neurons was recorded in rats exploring a 4-arm radial maze in which the local and distal cues could be manipulated. Cells from both regions exhibited place fields, although ventral subicular neurons had larger fields than hippocampal cells. Rotation of the local and distal cues in opposite directions produced movement of the place fields in either direction or a complete change in firing pattern. Simplifying the environment also produced changes in place field location. Despite similarities between regions, subiculum fields decreased in size whereas hippocampal fields increased in the simple environment. These findings suggest that subicular cells may receive converging input from several hippocampal neurons and code more complex configurations of the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intracerebroventricular insulin improves spatial learning and memory in male Wistar rats.

As one of the most studied protein hormones, insulin as well as its receptor have been known to play key roles in a variety of important biological processes. Detection of insulin and its receptor in the central nervous system (CNS) has led to a rapidly growing interest in the central effects of insulin. Insulin and its receptor are located in the specific area of the CNS with a diversity of region-specific functions different from its direct carbohydrate homeostasis in the periphery. The high density of insulin/insulin receptor in brain areas such as the hippocampus and cerebral cortex have shown to play an important role in higher cognitive functions, suggesting that insulin might be involved in the modulation of memory. Previous studies have offered controversial results regarding the effects of insulin on various types of memory. The aim of the present study is to determine whether intracerebroventricular (ICV) administration of insulin improves the water maze performance of rats. The experimental groups had pretraining insulin infusion (2, 4, 8, 16, and 32 mu) into the third ventricle, and then they were compared with a sham (saline) group. Insulin treatment caused an enhancing effect on spatial memory in a dose-dependent manner. The low doses (2, 4, and 8 mu) of insulin had no significant effect on the water maze achievement of rats, whereas higher doses (16 and 32 mu) significantly improved the rats’ performance. These results suggest that ICV administration of insulin may result in a dose-dependent improvement of memory function in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Object-recognition and spatial learning and memory in rats prenatally exposed to ethanol.

Prenatal ethanol exposure can produce cognitive and behavioral impairments. In the present study, rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment conditions were tested on the object-recognition delayed-nonmatching-to-sample (DNMS) task with nonrecurring items and on the spatial-navigation Morris water maze task. In Experiment 1, there were no significant differences among groups in object-recognition learning and memory, distractibility, or response perseveration on the DNMS task. In Experiment 2, the same rats were tested in the water maze; E rats took significantly longer to learn the task than did the PF or C rats. These data suggest that the mechanisms underlying spatial cognitive abilities are more vulnerable to the teratogenic effects of prenatal ethanol exposure than those underlying object-recognition abilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Oral methylphenidate improves spatial learning and memory in pre- and periadolescent rats.

Methylphenidate (MPD) is widely prescribed for attention-deficit/hyperactivity disorder in the United States. Patients, mostly school-age children, are taking the drug orally. To simulate the human condition, the authors used a cracker to administer methylphenidate orally (without the stress of handling) from Postnatal Day (PND) 22 to PND 40 and determined the effects of daily low-dose administration on the learning and performance of a radial arm maze win-shift task with all 8 arms baited. Number of entries to repeat, time to finish 8 entries, and days to reach criterion (at least 7 entries without errors for 4 out of 5 consecutive trials) were evaluated. An improvement during the first 7 days was revealed in both male and female rats treated with 3.0 mg/kg of oral methylphenidate compared with the controls. On PND 40, locomotor activity levels were not significantly different in the 3.0 mg/kg treated group compared with the controls during the initial 5 min or during the full 1 hr of recording. These data suggest that oral administration of low-dose MPD improves spatial learning and memory in both male and female preadolescent rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys.

Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected. (PsycINFO Database Record (c) 2011 APA, all rights reserved)