Recognition Memory In Rhesus Monkeys Research Articles

Two processes support visual recognition memory in rhesus monkeys

A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans.

Scopolamine impairs auditory delayed matching-to-sample performance in monkeys

Information concerning the major neurotransmitters critical for auditory memory is sparse. One possibility is the cholinergic system, important for performance in some tasks requiring visual short-term memory and attention [T.G. Aigner, M. Mishkin, The effects of physostigmine and scopolamine on recognition memory in monkeys, Behav. Neural. Biol. 45 (1986) 81-87; N. Hironaka, K. Ando, Effects of cholinergic drugs on scopolamine-induced memory impairment in rhesus monkeys, Jpn. J. Psychopharmacol. 16 (1996) 103-108; T.M. Myers, G. Galbicka, M.L. Sipos, S. Varadi, J.L. Oubre, M.G. Clark, Effects of anticholinergics on serial-probe recognition accuracy of rhesus macaques (Macaca mulatta), Pharmacol. Biochem. Behav. 73 (2002) 829-834; H. Ogura, T.G. Aigner, MK-801 Impairs recognition memory in rhesus monkeys: comparison with cholinergic drugs, J. Pharmacol. Exp. Ther. 266 (1993) 60-64; D.M. Penetar, J.H. McDonough Jr., Effects of cholinergic drugs on delayed match-to-sample performance of rhesus monkeys, Pharmacol. Biochem. Behav. 19 (1983) 963-967; M.A. Taffe, M.R. Weed, L.H. Gold, Scopolamine alters rhesus monkey performance on a novel neuropsychological test battery, Cogn. Brain Res. 8 (1999) 203-212]. Five rhesus monkeys were trained to perform an auditory go/no-go delayed matching-to-sample (DMTS) task wherein two acoustic stimuli (500ms), separated by variable memory delays (500ms, 2500ms, or 5000ms), were either identical sound presentations, i.e., match trials, or two different sound presentations, i.e., nonmatch trials. Sound stimuli were chosen semi-randomly from a large set sound set ( approximately 900). After reaching a criterion of 80% correct on the behavioral task, monkeys were injected with saline or doses of scopolamine hydrochloride mixed in saline (3 microg, 5 microg, and 10 microg per 1kg of weight), 30 min before training. Scopolamine impaired performance accuracy on match trials in a dose-dependent manner. Blocking muscarinic receptors with scopolamine did not significantly impair motor responses, food motivation, or responses to rewarded sound. These findings support the hypothesis that the cholinergic system is important for auditory short-term memory.

Crossed unilateral lesions of medial forebrain bundle and either inferior temporal or frontal cortex impair object recognition memory in Rhesus monkeys

In monkeys, section of the fornix, amygdala and anterior temporal stem results in a severe anterograde amnesia. Immunolesions of the cholinergic cells of the basal forebrain suggest that this amnesia is a result of isolating the inferior temporal cortex and medial temporal lobe from their cholinergic basal forebrain afferents. In this experiment, six monkeys were trained in a delayed match-to-sample task and then received a section of the medial forebrain bundle in one hemisphere and an ablation of either the frontal or inferior temporal cortex in the opposite hemisphere. All the animals were severely impaired in the performance of this task following this surgery, and the severity of the impairment was independent of the cortical area from which the medial forebrain bundle was disconnected. These results support a model of fronto-temporal interaction via the basal forebrain in new learning, in which midbrain sites related to reward modulate the cholinergic basal forebrain activity.

FK960, a novel potential anti-dementia drug, augments long-term potentiation in mossy fiber-CA3 pathway of guinea-pig hippocampal slices

Our previous studies have demonstrated that FK960 (FR59960; N-(4-acetyl-1-piperazinyl)- p-fluorobenzamide monohydrate), a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various animal models of amnesia in rats [M. Yamazaki, N. Matsuoka, N. Maeda, Y. Ohkubo, I. Yamaguchi, FK960 N-(4-acetyl-1-piperazinyl)- p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action, J. Pharmacol. Exp. Ther., 279 (1996) 1157–1173.] and in rhesus monkeys [N. Matsuoka, T.G. Aigner, FK960 [ N-(4-acetyl-1-piperazinyl)- p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine, J. Pharmacol. Exp. Ther., 280 (1997) 1201–1209]. To clarify the synaptic mechanisms of its antiamnesic action, FK960 was investigated for its effects on the development of long-term potentiation (LTP) in guinea-pig hippocampal slices. The magnitude of LTP of population spike recorded in CA3 pyramidal neurons was significantly augmented by perfusing FK960 (10 −9–10 −6 M) for 25 min before and during tetanic stimulation of the mossy fibers, whereas the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose–response curve was bell-shaped with a maximal augmentation at 10 −7 M. Scopolamine (10 −6 M) per se had little effect on the magnitude of LTP in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FK960 (10 −7 M). In hippocampal slices from animals treated with cysteamine (200 mg/kg, s.c.), which was shown to deplete the hippocampal somatostatin, FK960 (10 −7 M) hardly affected the LTP. These results suggest that FK960 enhances the magnitude of LTP in the mossy fiber-CA3 pathway through an activation of the cholinergic–somatostatinergic link in the hippocampal formation. Furthermore, it can be postulated that the drug regulates the cognitive function by modulating directly synaptic plasticity in the hippocampal neuronal network.

O-267 - FK960, a novel putative anti-dementia drug, improves visual recognition memory in rhesus monkeys

O-267 - FK960, a novel putative anti-dementia drug, improves visual recognition memory in rhesus monkeys

Effects of rhinal cortex lesions combined with hippocampectomy on visual recognition memory in rhesus monkeys.

1. We assessed the visual recognition abilities, as measured by delayed nonmatching-to-sample with trial-unique objects, of rhesus monkeys with hippocampectomy (i.e., removal of the hippocampal formation plus parahippocampal gyrus) combined with ablations of the rhinal cortex (i.e., entorhinal cortex plus perirhinal cortex). 2. Relative to unoperated controls, monkeys with combined hippocampectomy and rhinal cortex ablation (H+Rh) were significantly impaired in visual recognition. 3. Comparison of the scores of the monkeys in the present H+Rh group, which sustained near-complete rhinal cortex damage, with the scores of monkeys in an earlier H+Rh group in which the rostral part of the rhinal cortex had been spared indicates that the magnitude of the impairment is greater in the group with the more complete rhinal cortex damage. This finding is consistent with the idea that the rhinal cortex is critical for visual recognition. 4. Comparison of the present results with those from an earlier study on visual recognition that employed lesions limited to the rhinal cortex (Rh group) shows, paradoxically, that adding removal of the hippocampal formation and parahippocampal gyrus to a rhinal cortex lesion significantly reduces the recognition impairment produced by rhinal cortex lesions alone. 5. Our findings do not fit the view that the hippocampal formation, parahippocampal gyrus, and rhinal cortex constitute parts of a single functional system, such that the greater the damage to the entire system, the more severe the impairment. Instead, the results are consistent with the view that there are multiple functional subdivisions within the medial temporal lobe.

Postnatal development of CA3 pyramidal neurons and their afferents in the Ammon's horn of rhesus monkeys

Previous studies described the postnatal development of CA3 pyramidal neurons and their afferents in the rat. However, the postnatal development of the primate hippocampus was not previously studied. Thus, pyramidal neurons of the CA3 area of the monkey hippocampus were analyzed postnatally in the present study. At birth, a few thorny excrescences, the complex spines postsynaptic to mossy fibers, were found on the proximal segments of both apical and basal dendrites, whereas distal dendrites displayed pedunculate spines. Thorny excrescences increased in number until the third month. A continuous increase in the number of spines per unit length along the distal dendrites was observed during the first 12 months. The ultrastructural features of somata and dendrites of pyramidal cells in newborn monkeys were similar to those of adults. The analysis of the afferents to the CA3 pyramidal neurons was limited to the development of mossy fibers, the axons of granule cells, and myelinated axons in the alveus, stratum oriens, and stratum lacunosum-moleculare. At birth, most mossy fiber terminals were densely packed with synaptic vesicles and formed mainly axospinous synapses with CA3 pyramidal cells. By 1 month of age, the number of mitochondria and embedded spines increased to mature amounts. In the first postnatal month, degenerating axons and axon terminals were frequently observed in the mossy fiber bundles in stratum lucidum. The proportion of myelinated axons increased simultaneously in all three examined layers. At birth most axons were unmyelinated, whereas at 7 months of age the proportion of myelinated axons was similar to that found in adults. The present study indicates that most pyramidal neurons of the CA3 region in monkeys are in an advanced stage of development at the time of birth. Thus, mossy fibers from granule cells in the dentate gyrus have established mature-looking synapses, and the thorny excrescences of pyramidal cells that are postsynaptic to mossy fibers are also adult-like. Nevertheless, several of the adult features, such as the spine density of distal dendrites of pyramidal neurons and the myelination of afferent axons, develop during an extended period of time in the first year. The significance of this early anatomical maturation in a brain region involved in memory function is consistent with recent behavioral data that show a rapid postnatal maturation of limbic-dependent recognition memory in rhesus monkeys.

Effects of selective neonatal temporal lobe lesions on visual recognition memory in rhesus monkeys

Ten-month-old infant monkeys that had received neonatal ablations of either inferior temporal cortex (area TE) or the medial temporal region were compared with age-matched normal infant monkeys in visual delayed nonmatching-to-sample with trial-unique objects. Both types of early damage caused impairment in visual recognition, but the degree of deficit after early area TE lesions differed sharply from that after early medial temporal removals. Thus, whereas early medial temporal damage yielded a marked decline in visual recognition when the delays and lists were gradually increased, early area TE damage yielded normal recognition up to a delay of 60 sec and only mild impairment at longer delays and lists. The data indicate that, unlike adult monkeys, which suffer severe and nearly equivalent losses in visual object recognition after both types of ablation, the infant monkeys' recognition ability is largely spared after early damage to area TE but not after early damage to the medial temporal lobe. Together with recent clinical reports of profound memory loss in children with early dysfunction of the medial temporal region, the present findings demonstrate that medial temporal lobe structures operate early to sustain visual recognition memory, and recovery from early damage is limited at best. Early damage to higher-order visual cortex, however, can be largely compensated, presumably by one or more of the visual cortical areas that were left intact.

Comparison of the effects of scopolamine administered before and after acquisition in a test of visual recognition memory in monkeys

The effect of scopolamine on visual recognition memory in rhesus monkeys was assessed with a delayed nonmatching-to-sample task employing trial-unique stimuli. During the acquisition phase, 40 sample stimuli were presented sequentially. During the test phase, these same stimuli were presented in the reverse order, each paired with a novel stimulus. The animal was rewarded for choosing the novel stimulus in each pair. Two versions of this design were used. In Task 1, scopolamine (10.0 or 17.8 micrograms/kg) was administered 20 min prior to acquisition, which was followed immediately by the test phase. In Task 2, the drug was administered immediately after acquisition, which was followed 20 min later by the test phase. Performance was impaired in a dose-related manner in Task 1, but not at all in Task 2, indicating that the effects of scopolamine on performance cannot be attributed to an impairment either in the retrieval of stored information or in the attentive or perceptual discriminative processes needed for such retrieval, or, by implication, for storage. In addition, the forgetting curves for scopolamine in Task 1 were parallel to those of the control sessions; i.e., the curves did not diverge with increasing delay intervals, indicating that scopolamine did not increase the rate of forgetting. Taken together, the results suggest that scopolamine interferes selectively with the initial storage of the information to be remembered.