Robert W. Flint

Anterior rhinal cortex and amygdala: dissociation of their contributions to memory and food preference in rhesus monkeys.

Rhesus monkeys were trained on 2 versions of delayed nonmatching-to-sample, one with multiple pairs of objects and the other with a single pair, to evaluate their ability to remember objects. They then received either bilateral aspiration lesions of the anterior rhinal cortex or bilateral excitotoxic lesions of the amygdala, or were retained as unoperated controls. On re-presentation of the multiple-pair task, monkeys with anterior rhinal cortex lesions failed to show the improvement observed in both other groups in remembering the objects over delay intervals ranging from 10 to 60 s. Also, monkeys with anterior rhinal cortex lesions were impaired relative to the controls in relearning the single-pair version of the task. Conversely, on a formal test of food preference, monkeys with amygdala lesions showed abnormal patterns of food choice, whereas monkeys with anterior rhinal cortex lesions did not. Visual memory impairments formerly attributed to amygdala damage are probably due to the rhinal cortex damage associated with aspiration lesions of the amygdala.

MK-801 induced retrieval, but not acquisition, deficits for passive avoidance conditioning

Two experiments using a state-dependent retention (SDR) design determined whether MK-801 blocked the acquisition and retention of an avoidance response. In Experiments 1 and 2, rats were trained and tested 30 min after injections of either saline or MK-801 (0.05 and 0.10 mg/kg, respectively). Two minutes after training, subjects were immediately tested, and in both experiments, the avoidance response was acquired. The 24-h retention tests for Experiment 1 revealed that the data marginally supported a SDR interpretation. In Experiment 2, the dose of MK-801 was increased to 0.10 mg/kg, and the results showed that MK-801 rendered passive avoidance (PA) state-dependent. These experiments indicate that neither the 0.05 nor 0.10 mg/kg doses of MK-801 prevented acquisition of the avoidance response and that the latter dose rendered memory for PA training state-dependent. It is suggested that doses of MK-801 that did not impair PA learning can function as a cue state and influence expression of memory for PA.

Glucose effects on a continuous performance test of attention in adults

Increases in plasma blood glucose levels modulate memory, mood, and, to some extent, attention in adults. Participants in the present study were administered glucose (10, 100, and 500 mg/kg, or 50 g) or placebo (23.7 mg saccharin) shortly prior to completing the test of variables of attention (TOVA), a continuous performance test (CPT) commonly used to assess attention for diagnostic purposes. There were significant increases in blood glucose levels for the 500 mg/kg and 50 g groups, but only the 100 mg/kg group showed significant changes in behavior in comparison to the saccharin group. Specifically, the 100 mg/kg group performed worse on measures of commission errors, post-commission responses, and post-commission response time variability. There were no differences among the groups on other major variables of attention, including omission errors, response time, and response time variability. The results of this study demonstrate that large doses of glucose which increase blood glucose levels do not influence attention, but that a moderate dose (100 mg/kg) selectively impairs measures of impulsivity or disinhibition. Practitioners and researchers should maintain an awareness of dietary effects on attention and continue to examine micronutrients as potential confounds on diagnostic tests of cognition and behavior.

Differential effects of glucose on modulation of emotional and nonemotional spatial memory tasks

Research examining the memory-enhancing effects of glucose in humans has been limited to mnemonic tasks lacking affective components, even though glucose may be a mechanism for emotioninduced memory enhancement. This limitation does not permit analysis of interactions between the enhancing properties of emotional stimuli and glucose. Participants were administered either glucose or saccharin 15 min prior to completing a neutral or emotional spatial memory task. Performance under three glycemic conditions (100 mg/kg or 50 g glucose, or placebo) for the two sets of emotional stimuli revealed a significant interaction. Both 100-mg/kg and 50-g doses of glucose resulted in impaired performance for emotional stimuli. For neutral stimuli, a 100-mg/kg dose enhanced memory, whereas a 50-g dose showed no effect. Results indicate that the enhancing effects of emotional stimuli may be attenuated by the consumption of glucose and suggest that recent food consumption should be considered in paradigms examining memory.

Elevated glucose metabolism in the amygdala during an inhibitory avoidance task

There is a long-standing debate as to whether the memory process of consolidation is neurochemically similar to or the same as the set of processes involved in retrieval and reconsolidation of that memory. In addition, although we have previously shown that initial memory processing in the hippocampus causes a drainage of hippocampal glucose because of increased local metabolic demand, it is unknown what metabolic changes occur elsewhere in the brain or during subsequent processing of a previously consolidated memory. Male Sprague Dawley rats (3 months old) were implanted with unilateral microdialysis cannulae and in vivo microdialysis of amygdala extracellular fluid (ECF) was performed during both (i) initial learning and (ii) retrieval 24 h later of an aversively motivated avoidance memory task. ECF samples were analyzed for glucose, lactate, pyruvate and glutamate. Results showed close similarity between increases in local glycolysis seen during both consolidation and retrieval, but also suggested that there may perhaps be a difference in amygdalar oxidative phosphorylation stimulated by the two processes. Hence, our data suggest that memory formation places similar metabolic demands across neural systems, and that consolidation may be metabolically different from retrieval.

Glucose administration attenuates hypothermia-induced retrograde amnesia in rats in a time- and dose-dependent manner

It is well established that posttraining administrations of glucose enhance memory in a time- and dose-dependent manner. More recently, glucose has also been found to attenuate scopolamine-induced anterograde amnesia, displaying the same time- and dose-response characteristics (Stone et al., 1988). In the present study, the use of glucose as an agent for alleviation of hypothermia-induced retrograde amnesia was examined. In each experiment, animals were given a single trial of passive avoidance conditioning. Retrograde amnesia was induced through hypothermia immediately following training. All injections were given immediately following hypothermia treatment, and tests for fear retention were administered 24 h following training. In Experiment 1, the dose-response effects of glucose (10, 100, or 400 mg/kg) were examined; in Experiment 2, the time-dependent effect of 100 mg/kg of glucose administered immediately, 1, or 2 h after hypothermia was examined. The results show that glucose injections attenuate retrograde amnesia in both a dose- and time-dependent manner. These results coincide with the growing body of evidence supporting the memory-modulating effects of glucose.

Cycloheximide impairs reconsolidation of a contextually reactivated memory in a conditioned taste aversion paradigm.

Rats were used to examine the impact of systemic protein synthesis inhibition (PSI) on the reconsolidation of a contextually reactivated memory of conditioned taste aversion (CTA). Rats were administered intraperitoneal injections of saline or lithium chloride (LiCl; .15 M) following exposure to a novel sucrose solution in a unique context. Seven days later, rats were injected subcutaneously with saline or cycloheximide (CXM; 1 mg/kg) and returned to their home cage or placed into the CTA training context in the absence of the target conditioned stimulus to reactivate the training memory. At testing, LiCl-trained rats that had been given CXM at reactivation had significantly greater difference scores (sucrose-water) in comparison with LiCl/CXM rats that had not been given a reactivation treatment and LiCl/saline memory-reactivated rats. These results suggest that context re-exposure effectively reactivates memory of CTA training that may be weakened through PSI. Extinction tests revealed rapid attenuation of taste aversions in all of the LiCl-injected groups. The involvement of taste-potentiated aversions and the role of the context in taste aversion conditioning are discussed.

Stress-induced memory enhancement for inhibitory fear conditioning in rats

The retroactive effects of stress on memory have not received a great deal of empirical attention; however, the research that has been conducted has reported both positive and negative effects of stress on memorial processes. The goal of this study was to examine the effects of a naturalistic Stressor—an intense bout of exercise—on memory for inhibitory fear conditioning in rats. Experiment 1 investigated the retroactive effect of a stressful swim treatment on memory for passive avoidance (PA) training. Rats that received an immediate posttraining swim treatment demonstrated a significant enhancement in performance when tested for retention 24 h later. Furthermore, the enhancing effect of the swim treatment was time dependent: Rats receiving the swim treatment 15 min after PA training no longer exhibited reliably better scores than did rats not receiving the swim treatment. Experiment 2 used preexposures to control for the possibility that the swim treatment was enhancing avoidance scores by acting as a punisher rather than a memory modulator. Results indicate that both the group that was preexposed and the group that was not preexposed showed reliably higher scores than did a group of animals receiving only PA training, thus replicating Experiment 1. Furthermore, the results of Experiment 2 suggest that swimming was not simply acting as a punishing agent, since preexposures to the treatment did not attenuate its memory-enhancing properties. The possible role of stress-related hormones on memory processes is considered.

Glucose enhancement of face recognition is unaffected by alterations of face features

Glucose improves memory on a variety of tasks has been well established in both the animal and human literature. Of particular relevance to the present experiment is the finding that administration of glucose improves face recognition performance in both healthy, young adults and in Alzheimers patients. This experiment attempted to expand on these findings to determine if glucose-enhanced performance for face recognition is specific to certain face features (e.g., nose, eyes, or hair). In a between subjects experiment that tested healthy, young adults, a pre-training administration of glucose (50 g) was shown to improve face recognition performance relative to placebo (27.3mg saccharin); however, the significant improvement on the task was not specific to a particular feature. This result suggests that glucose did not enhance memory for individual face features, but rather enhanced overall memory for face stimuli.

UCS intensity-dependent attenuation of infantile amnesia

Unconditioned stimulus (UCS) reactivation treatments may attenuate infantile amnesia in rats by providing an external reminder cue, creating an internal contextual reminder cue via endogenous hormones, and/or modulating memory retrieval via neurochemical changes from activation of the stress cascade. In the present study, the UCS reactivation treatment and the relationship between intensity at training and intensity at testing were examined. In Experiment 1, 17-day-old Sprague-Dawley rats were given multiple-trial passive-avoidance conditioning with a high-intensity footshock. Those subjects administered a high-intensity reactivation treatment performed significantly better than did subjects that received a low-intensity reactivation treatment, subjects that received no treatment, or pseudo-trained animals. Experiment 2 repeated the first experiment with a low-intensity training footshock. The results indicated that only a high-intensity reactivation treatment attenuated infantile amnesia. These findings suggest that the training UCS need not match the reactivation treatment in terms of intensity and leaves open the possibility that aversive reactivation treatments may be multifaceted, involving external contextual cues, internal contextual cues, and neuromodulatory effects from activation of the stress cascade.