Transient memory impairment in monkeys with bilateral lesions of the entorhinal cortex

Performance on five behavioral tasks was assessed post-operatively in Macaca fascicularis monkeys prepared with bilateral lesions of the entorhinal cortex (E group). Three of the tasks were also readministered 9-14 months after surgery. Initial learning of the delayed nonmatching-to-sample (DNMS) task was impaired in the E animals relative to unoperated control monkeys. On the delay portion of DNMS, the performance of E animals was nearly at control levels at short delays (up to 60 sec) but was impaired at 10 min and 40 min retention intervals. On the retest of DNMS, the E animals performed normally at all retention intervals. The E animals were unimpaired on the four other memory tasks. Neuroanatomical studies revealed a significant transverse expansion of the terminal field of the perirhinal cortical projection in the CA1 region of the hippocampus. Compared to unlesioned, anatomical control monkeys, the transverse length of the perirhinal terminal field in CA1 increased approximately 70% in the E monkeys. Although this was a striking morphological alteration, it is not known whether the sprouting of this projection influenced the behavioral recovery. The results of these studies suggest that the entorhinal cortex may normally participate in the learning and performance of tasks that are dependent on the medial temporal lobe memory system. However, recovery of normal DNMS performance demonstrates that the entorhinal cortex is not, by itself, essential for learning and performance of such tasks.     

Effects of ibotenate hippocampal and extrahippocampal destruction on delayed-match and -nonmatch-to-sample behavior in rats

The effects of ibotenate lesions of the hippocampus (HIPP) or hippocampus plus collateral damage to extrahippocampal structures (HCX) were investigated in rats trained to criterion on spatial versions of either a delayed-match (DMS) or delayed-nonmatch-to-sample (DNMS) task. After recovery from surgery, animals were retrained at "0" sec delays, then assessed at 0-30 sec delays for 15 d, retrained again at 0 sec delays, and retested for another 25 d on 0-30 sec delays. Pretrained HIPP-lesioned animals showed marked delay-dependent deficits in both tasks that never recovered. Detailed examination of within- and between-trial performance factors, including changes in response preferences, length of previous trial delay, and sequential dependencies, revealed important factors operating in lesioned animals that were either absent or insignificant before the lesion. Pretrained HCX-lesioned animals showed deficits similar to those of HIPP animals, with the noticeable exception of a strong "recency" influence of the previous trial. Another group of HIPP- and HCX-lesioned animals trained on the tasks after the lesion showed reduced impairments of the type described above, suggesting that extrahippocampal structures trained after the lesion can assume the role of the hippocampus to some degree. The findings indicate that both the type of lesion and the previous history of the animal determine the postlesion DMS and DNMS performance of animals suffering damage to the hippocampus and/or related structures.     

Glutamate receptor-mediated restoration of experience-dependent place field expansion plasticity in aged rats.

Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally induced expression of neuronal plasticity uses an NMDAR-dependent, LTP-like mechanism and could be used by hippocampal networks to store information. Aged spatial memory-impaired rats exhibit defective experience-dependent place field expansion plasticity. One possible explanation for this aged-associated deficit is alterations in glutamatergic function. In fact, both NMDAR- and AMPAR-mediated field excitatory postsynaptic potentials in CA1 decrease with aging. The current study investigated whether modulation of either AMPA or NDMA receptor activity could restore this experience-dependent plasticity by prolonging AMPAR activity with the ampakine CX516 and modulating the NMDAR with the noncompetitive antagonist memantine. The spatial firing characteristics of multiple CA1 pyramidal cells were monitored under both treatment conditions as aged rats repeatedly traversed a circular track. Compared to the saline baseline condition, acute administration of memantine, but not CX516, reinstated experience-dependent place field expansion. Taken together, these data suggest that pharmacological manipulation of the NMDAR can improve the function of hippocampal networks critical to optimal cognition in aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pyrithiamine-induced thiamine deficiency impairs object recognition in rats.

Pyrithiamine-induced thiamine deficiency (PTD) in rats is used to model the etiology, diencephalic neuropathology, and memory deficits of Korsakoff's amnesia. We assessed the performance of rats exposed to PTD on a test of object recognition—nonrecurring-items delayed nonmatching-to-sample (DNMS). PTD produced thalamic lesions similar to those of Korsakoff's amnesics and similar to those previously observed in PTD rats. PTD rats required more trials to master DNMS at a 4-sec retention delay than did controls, and after they had done so, they performed more poorly than controls at delays of 15, 30, 60, and 120 sec. DNMS deficits were also observed in PTD rats that received training prior to PTD treatment. These findings support the validity of the PTD rat model of Korsakoff's disease by demonstrating that PTD rats display object-recognition deficits that are similar to those reported in Korsakoff amnesics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of spatial but not object-recognition memory by neurotoxic lesions of the dorsal hippocampus in rats.

Ischemia-induced cell loss in the CA1 region of the dorsal hippocampus results in severe deficits on delayed non-matching-to-sample (DNMS), whereas hippocampectomy produces little or no impairment, suggesting that partial hippocampal damage is more detrimental to DNMS performance than total ablation. To test this hypothesis, rats with or without preoperative DNMS training were given partial cytotoxic lesions of the dorsal hippocampus. When tested, neither group displayed any DNMS deficits despite widespread cell loss in the CA1 and other regions of the dorsal hippocampus. In the final experiments, rats tested previously on DNMS were found to be impaired on the Morris water maze. The finding that partial hippocampal lesions disrupt spatial memory while leaving object-recognition memory intact indicates a specialized role for the hippocampus in mnemonic processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated acquisition of behavioral chains: effects of methylphenidate and imipramine

A method involving repeated acquistion of behavioral chain was used to assess the effects of methylphenidate and imipramine in individual animals. Pigeons obtained food for completing a 4-response chain, which was changed from session to session. Learning was defined by the decrease in errors across trials within a session; overall accuracy was measured by total errors per session. For comparison, the drug tests were also conducted under a performance condition, in which the 4-response chain was the same from session to session. In general, both drugs increased total errors per session as a function of dose under both the learning and performance conditions. The error-increasing effect was greater with imipramine than with methylphenidate and was detected at lower doses under the learning condition than under the performance condition. Under the learning condition, the higher doses of both drugs decreased the rate of within-session error reduction. Although neither drug enhanced accuracy at any of the doses tested, the lower doses of methylphenidate slightly decreased total trial time under both the learning and performance conditions.     

Rhinal cortex lesions and object recognition in rats.

Tested 11 male rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition (OR) in monkeys. The rats were tested at retention delays of 4, 15, 60, 120, and 600 sec before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-sec delay but were impaired at delays of 15 sec or longer. The addition of bilateral amygdala lesions did not increase their DNMS deficits. The present finding of a severe DNMS deficit following rhinal cortex damage is consistent with the authors' previous finding that bilateral lesions of the hippocampus cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D. G. Mumby et al, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in OR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ischemia-induced object-recognition deficits in rats are attenuated by hippocampal ablation before or soon after ischemia.

The literature on the role of the hippocampus in object-recognition contains a paradox: Transient forebrain ischemia (ISC) produces hippocampal damage and severe deficits on the delayed nonmatching-to-sample (DNMS) task, yet hippocampal ablation (ABL) produces milder deficits. Experiment 1 confirmed that pretrained rats display severe DNMS deficits following ISC, but not ABL. Ischemia produced loss of CA1 neurons. but no obvious extrahippocampal damage. In Experiments 2 and 3, ISC rats from Experiment 1 received ABL. and ABL rats received ISC: neither treatment affected DNMS performance. In Experiment 4, rats that received ISC followed 1 hr later by ABL displayed only mild deficits. It is hypothesized that ISC-induced DNMS deficits are due to extrahippocampal damage produced by pathogenic processes that involve the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-microliter infusion containing 5.0 microgram of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean +/- SEM number of conditioned responses (CRs) during retention test session was 16.47 +/- 1.78 in the vehicle group and 9.93 +/- 1.59 in the AP5 group; P < 0.05). Post-training infusion of AP5 did not affect retention (mean +/- SEM number of conditioned responses during retention test session was 18.46 +/- 1.94 in the vehicle group and 20.42 +/- 2.38 in the AP5 group; P > 0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.     

Lesions of the frontal cortex, hippocampus, and intralaminar thalamic nuclei have distinct effects on remembering in rats.

Lesions of the intralaminar thalamic nuclei (ILn), the medial wall (MW) area of prefrontal cortex, and the hippocampus were compared and found to have distinct effects on delayed matching-to-sample (DMS) and delayed non-matching-to-sample (DNMS) tasks based on different types of stimulus cues. Hippocampal lesions impaired DNMS trained in a radial arm maze but had little effect on DMS trained with retractable levers or olfactory DNMS. MW lesions affected the DMS task but had limited effects on olfactory DNMS and radial arm maze DNMS. ILn lesions resulted in a more generalized pattern of impairment for radial maze tasks and (in previous studies) for the DMS and olfactory DNMS tasks. Only the hippocampal lesion was associated with a delay-dependent impairment. It is argued that ILn lesions disrupt remembering through their effects on the recurrent, feedback pathways that link functionally related areas of the basal ganglia and cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement of effects of dopaminergic agonists on neuronal activity in the caudate-putamen of the rat following long-term d-amphetamine administration

Amphetamine- and apomorphine-induced changes in the activity of neurons in the caudate-putamen of paralyzed, locally anesthetized rats were recorded in animals pretreated with 2.5 mg/kg d-amphetamine sulphate for 6, 18 or 36 days, or in animals pretreated with saline for 36 consecutive days. In saline-pretreated animals, 2.5 mg/kg d-amphetamine sulphate (IP) produced an initial, brief potentiation of neuronal firing that was followed by a marked depression of neuronal activity lasting for approximately 35 to 110 min after injection. In amphetamine-pretreated animals, this depression of neuronal activity to the same dose of the drug was markedly prolonged, especially in animals given 36 consecutive days of d-amphetamine pretreatment. A similar enhancement occurred in response to 0.25 mg/kg apomorphine (IP) in animals pretreated with amphetamine for 36 days compared to saline-pretreated control animals. These results are discussed in relation to the known behavioral and biochemical effects of acute and long-term amphetamine administration.     

Short-term object recognition memory in the rat: Nonmatching with trial-unique junk stimuli.

A delayed nonmatching-to-sample (DNMS) task with trial-unique stimuli, similar to that used to test object recognition memory in primates, was adapted for use with rats. For each trial of the DNMS task, two stimuli were randomly selected from a pool of 250 small "junk" objects; one member of the pair was designated as the sample. On the first part of a trial, the rat traversed an elevated runway and displaced the sample for food reward. After a 10-s delay, the rat again traversed the runway to choose between the previously presented sample and the second member of the pair. Reward on the choice trial followed selection of the new object. Scores on the first day of DNMS were significantly above chance, and animals could consistently perform at approximately 75% accuracy. Extending the delay to 30 or 120 s lowered choice accuracy, but performance was still above chance. The DNMS task for rats, unlike most other memory tests for rodents, does not require memory for spatial location. The similarity to tests used with primates should allow for more direct comparison of results of memory research across species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Infant imitation: The sensory-motor agenda.

Six different actions were demonstrated by the 2nd author to 9 infants once a month between the ages of 6 and 12 mo. Each action was presented many times, with each trial contingent on the S's making eye contact with the experimenter. From videotapes, 21 categories (CAs) of infant behavior were coded continuously. Each CA could be considered a component act or feature of one of the modeled actions. All CAs were coded during all parts of the session: baseline periods, trials of the tasks of which they were features, and trials of the other tasks. Ss did not confine their performance of features to the relevant trials as construed by the authors, but they did accelerate or introduce features for the first time during those trials. Analysis showed that the Ss "worked up to" precise imitations by accommodating themselves to the features in a consistent order over both months and trials. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks

In this study a rat self-administration model was used to examine the effects of training dose and time in the session on the dose-effect curve for heroin. Doses of heroin lower than 5.4 microg/inf maintained higher rates of drug intake in animals trained with 5.4 microg/inf compared to 18 microg/inf. Doses greater than 5.4 microg/inf maintained similar rates of intake in both groups of animals. The dose-response curve was shifted downward and to the right as the session progressed for animals trained with 5.4 microg/inf of heroin; however, the shift in the dose-intake curve over the session was less pronounced when the training dose was 18 microg/inf. Naltrexone and naltrindole were administered to animals in which responding was engendered with infusions of 5.4 microg of heroin to determine the effects of these antagonists in the context of time is the session. The potency of naltrexone decreased across the 4 h of the session with a time course that was consistent with literature reports on the elimination kinetics of naltrexone in rat brain. In contrast, there was not a significant interaction between naltrindole dose and session time. Therefore, the rates of heroin intake in rats are dependent not only upon the dose available for self-administration, but upon the session time and training dose as well.     

Sequence of single neuron changes in CA1 hippocampus of rabbits during acquisition of trace eyeblink conditioned responses

The sequence of changes in single neuron activity in the CA1 area of the rabbit hippocampus was examined during daily sessions (80 trials/session) of hippocampally dependent nonspatial trace eyeblink (i.e., nictitating membrane response) conditioning. Each trial for trace conditioned animals (n = 7) consisted of a tone conditioned stimulus (CS; 6 kHz; 90 dB, 100 ms) followed by a 500-ms silent trace period, then a corneal airpuff unconditioned stimulus (US; 3.0 psi; 150 ms). Control animals (n = 5) received unpaired CSs and USs. Most pyramidal (n = 309) and theta (n = 21) cells were recorded for a single day of training. The activity of cells for each animal were grouped according to: the day of training that CRs began to increase and the day of training that CR performance became asymptotic. Pyramidal cells from trace conditioned animals demonstrated several stages of learning-related activity: large increases in activity after both the CS and US early in conditioning on the day of training when CRs began to increase, smaller moderate increases in activity on the following days of training, and decreases in activity after the US during asymptotic CRs. Pyramidal cell-increases declined significantly across the trials of each daily session. Theta cells showed an activity pattern opposite to the pyramidal cells, consistent with the notion that theta cells have an inhibitory influence on pyramidal cells. Single pyramidal cells also were categorized into response profiles. Most pyramidal response profiles showed increases in activity specific to the day of initial CRs. Two of the pyramidal response profiles may be involved in assessing the temporal properties of the CS-US trace conditioning trial.     

The effects of electrolytic lesion to the shell subterritory of the nucleus accumbens on delayed non-matching-to-sample and four-armed baited eight-arm radial-maze tasks.

The effects of bilateral electrolytic lesions of the "shell" subterritory of the nucleus accumbens in the rat were examined on 2 tasks known to be sensitive to hippocampal damage. Experiment 1 tested the effects of shell lesion on delayed non-matching-to-sample (DNMS) task in a T-maze. The maze was rotated 180° after the end of acquisition. Experiment 2 used a 4-arm baited, 4-arm unbaited, 8-arm radial-maze task and its reversal. Shell lesion led to impaired acquisition of DNMS in a T-maze and of 4-arm baited, 4-arm unbaited, 8-arm radial maze tasks, suggestive of mnemonic deficits. Following analysis of animals' choice pattern in both tasks, the deficit was interpreted as being largely due to an extensive use of response strategy. The results suggest that the inappropriate use of response strategy by shell animals was a result of their inability to switch from initial response strategy to a later, more appropriate, memory-dependent strategy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stability of everyday memory in age-associated memory impairment: A longitudinal study.

Everyday memory performance was examined longitudinally in 2 groups of Ss meeting the diagnostic criteria for age-associated memory impairment (AAMI). One group of 157 participants in a drug trial for reversing memory loss in AAMI was tested over multiple sessions. The other group of 75 persons did not participate in a drug trial and thus was tested only twice. Both groups were retested for longitudinal follow-up about 4 yrs after initial session. Follow-up test performance remained fairly stable relative to initial performance in both groups. The drug study group showed large practice effects during the course of the drug studies, but these effects subsided after the drug studies' end. Implications regarding memory decline in the normal elderly and neuropsychological measurement issues are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maturation of spatial delayed responses to auditory cues in kittens.

Tested 40 mongrel cage-reared kittens in 4 age groups (45, 60, 120, or 180 days) for locomotor delayed responses to auditory cues in a 2-choice situation. Each S was trained for 15 days (300 trials); delays of 5 different durations (0-27 sec) were randomly given in each session. Performance did not improve as a function of age. All groups showed some immediate capacity for the task, all improved with training, and in all ages more errors were made after longer than after shorter delays. The ability to remember the locus of a brief sound over short periods of time appears to be mature before weaning in kittens. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recombinant human growth hormone decreases lung and liver tissue lipid peroxidation and increases antioxidant activity after thermal injury in rats

The effects of pulsed direct current (dc) electric fields on the frequency of spontaneous bursting in a model epileptic focus were studied. The high potassium hippocampal slice model was used to generate spontaneous burst firing activity similar to interictal spikes in the pyramidal cell layer of CA3. Electric fields were generated from platinum subdural electrodes placed in the perfusion bath. Three hundred and seventy-eight experimental trials were performed on 10 hippocampal slices from 10 rats and the effects of field polarity, field strength and duration of stimuli on firing frequency was examined. Hippocampal slices were oriented horizontally with the CA3 layer towards the positive electrode, the average interburst interval did not correlate significantly with polarity of the delivering pulses (one-way ANOVA, p = 0.96). Average interburst interval showed a significant correlation with pulse duration of 200 and 400 msec (p = 0.030 and p = 0.004, respectively). As a function of field strength, there were significant average interval changes for fields of 33, 46, and 73 mV/mm (p = 0.024, p = 0.001 and p = 0.001, respectively). In conclusion, CA3 burst firing activity in high potassium concentration can therefore be altered by electric fields.     

Long-term proactive interference and novelty enhancement effects in monkey list memory.

Serial-probe-recognition (SPR) performance by 2 monkeys deteriorated over several months of training. Three hundred and twenty different items were presented without repetition within a session (trial unique) but were repeated between sessions. The cause of the deterioration was identified as proactive interference (PI) due to repetitive use of items from day to day. Introduction of novel stimuli across days improved performance from 63% to 82% correct (Experiment 1). Tests with only probe items and no list items (Experiment 2) revealed that the monkeys were using a familiar/novel response strategy in combination with a relational strategy (relating the probe item to the list items) to further improve their SPR performance. Intermixing familiar baseline trials and novel transfer trials within a session (Experiment 3) encouraged the subjects to use a relational strategy, and it improved performance on baseline trials as well as on transfer trials. Possible qualitative similarity between the relational strategy and the familiar/novel response strategy is discussed along with theoretical implications of these findings for experiments which have used small number of repeating stimuli within a session. (PsycINFO Database Record (c) 2010 APA, all rights reserved)