Single unit activity in the auditory cortex of a monkey performing a short term memory task

Summary Short term memory to tones (STMT) was investigated by recording single unit activity in the auditory cortex of a behaving monkey. The activity of each unit was studied in two behavioral conditions: a) During task performance, the monkey had to compare two tones separated by one second of silence (inter-stimulus interval), b) During a nonperforming period; the monkey heard the two tones but did not respond behaviorally. It was noted that the firing rate of many units during the inter-stimulus interval (ISI) was dependent on the frequency of the first tone. Such dependency was observed even towards the end of the ISI, both during task performance trials (50% of the units) and during the nonperforming period (32% of the units). The activity of these units could be the basis of STMT in both of these behavioral states. In 65% of all the units tested, the responses during the ISI were of a higher magnitude in the performance period than were the responses in the non-performance period. The activity of these units may be related either to general processes such as attention and expectation or to short-term memory processes. During task performance, the responses of 23% of the units to the second tone were dependent on whether its frequency was identical to that of the first tone. Such dependency was never observed during the non-performing period. These units may detect similarity or non similarity between two tones presented one second apart. Periodic patterns of firing were not found in the study, thus suggesting that the ISI responses were not generated by reverberatory activity in simple closed loops. On the basis of these results, several alternative mechanisms of STMT are suggested.     

Pulpal reactions to glutaraldehyde and paraformaldehyde pulpotomy dressings in monkey primary teeth

Abstract Pulpotomy was performed in primary teeth of 4 vervet monkeys to compare the effect of an experimental dressing containing glutaraldehyde (GL) to a similar formula with paraformaldehyde (PF). Forty teeth were examined histologically 2 weeks to 5 months post-operatively. In the PF group, calcifications were more frequently observed and the central core of tissue in the root canal was heavily laden with debris. Pathologic apical resorption and lesions were more frequent. The pulp in the apical third of the root canal was usually uninflamed in the GL group and peripheral calcifications were seldom observed in it. Reaction to GL seemed, therefore, more favorable clinically. Defects were not observed in the permanent teeth that erupted following shedding or extraction of the experimental primary ones of either group.     

Oral self-administration of etonitazene in rhesus monkeys: Use of a fading procedure to establish etonitazene as a reinforcer

The establishment of orally delivered etonitazene (a potent opioid) as a reinforcer, was studied in eight rhesus monkeys. Initially, when given concurrent access to 2.5 μg/ml etonitazene and the water vehicle, five of the monkeys rejected the drug, whereas the other three monkeys consumed more drug solution than water. The five monkeys that rejected the drug solution underwent an acquisition phase to establish the drug as a reinforcer. A fading procedure was used to transfer control of responding from a 2% (wt/vol) ethanol solution to a 2.5 μg/ml etonitazene solution. Initially, responding was maintained by contingent deliveries of 2% ethanol. Next, across blocks of six or more sessions, increasing amounts of etonitazene were added in steps to the 2% ethanol solution. Subsequently, the 2% ethanol solution was decreased in steps to zero, leaving only the 2.5 μg/ml etonitazene present. When the fading procedure was completed, dose of etonitazene was varied by increasing the volume delivered, first under fixed ratio (FR 4) and then under an FR 8 reinforcement schedule. The same dose manipulations were made with the three monkeys who did not undergo the fading procedure because they preferred etonitazene over water when first tested. Etonitazene was established as a reinforcer for six of the eight monkeys because drug deliveries exceeded vehicle deliveries across a range of drug doses.     

Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey.

In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age-related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age-related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age-related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364-376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2-minute delay. It is proposed that age-related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in cognition occur because the conduction velocity along the affected nerve fibers is reduced, so that the normal timing sequences within neuronal circuits break down.     

Inoculation of Rhesus Monkeys with Human Helicobacter pylori: A Long-term Investigation on Gastric Mucosa by Endoscopy

Abstract: To study the pathogenetic role of Helicobacter pylori, colonization of this organism was attempted in conventional rhesus monkeys. After inoculation of human H. pylori to the gastric mucosa of four 10-year-old monkeys, endoscopical and histological examinations were repeated for 10 weeks. The organisms were recovered bacteriologically from all 4 monkeys at the first week, from 3 animals at the 2nd, and from 2 animals at the 6th to 10th week. The endoscopical examination showed only minimum changes in the mucosal appearance such as erythema and erosion due to H. pylori colonization throughout the study. In contrast, the histological examination revealed prominent polymorphonuclear cell infiltration, edema of the mucosa and dissected epithelium at the earlier periods and mononuclear cell infiltration afterwards. The maximum lymphocyte reaction such as clusters or the formation of a thick layer at the bottom of the lamina propria was observed at the 8th week. These results indicated that rhesus monkeys can be infected by human H. pylori resulting in similar pathologic changes in the human stomach, and that this animal model may be useful for future studies.     

Concurrent self-administration of ethanol and an alternative nondrug reinforcer in monkeys: effects of income (session length) on demand for drug

Eight rhesus monkeys (Macaca mulata) were trained to self-administer orally delivered ethanol (8%) and saccharin (0.03 or 0.3% wt/vol) or water under concurrent fixed-ratio (FR) schedules. The FR requirement for saccharin was fixed at 32, while the FR for ethanol was varied (4, 8, 16, 32, 64 and 128) in a nonsystematic order to assess demand for drug. Demand was defined as consumption plotted as a function of price (FR). Income was defined as the duration of access to available resources. Income was varied by allowing access to the concurrently available liquids 20, 60 or 180 min per day. Order of testing was counter-balanced across monkeys. Saccharin deliveries were much higher than ethanol deliveries under the 180-min income condition; however, they were lower than ethanol deliveries when income was reduced to 20 min and the ethanol FR was 4, 8 or 16. Thus, when the price of drug was relatively low, consumption of drug exceeded that of the nondrug reinforcer, and that relationship was reversed as income decreased. Saccharin deliveries sustained a proportionally greater reduction due to decreased income compared to ethanol deliveries. As income decreased from 180 to 20 min, saccharin deliveries were reduced by an average of 79.1% (across ethanol FR conditions) while ethanol deliveries were reduced by an average of 41.2 and 40.8% when concurrent saccharin or water were available, respectively; thus, drug self-administration was more resistant to income changes than saccharin. The demand for ethanol was shifted downward in a parallel fashion as income decreased. As ethanol cost (FR) increased, there were proportionately greater decreases in ethanol intake when saccharin was concurrently available compared to when water was available. There was a 35–50% reduction in ethanol deliveries due to concurrent saccharin (versus water) at FR 4, compared to a 55–75% reduction at FR 128. Cost of ethanol (FR), income level and the availability of a nondrug reinforcer are all variables that modify ethanol-reinforced behavior, and income alters the relative preference for a drug versus nondrug reinforcer.     

Molecular features of theTSPY gene of gibbons and Old World monkeys

Restriction pattern, chromosome localization and the sequence of the testis-specific gene,TSPY, were investigated in the white-handed gibbon, agile gibbon, siamang, hamadryas baboon and Japanese monkey. Southern blot analysis showed theTSPY gene to be male specific in the primates used and disclosed variability of restriction pattern in gibbons. Fluorescencein situ hybridization demonstrated that the probe ppTSPY2372, biotinylated using polymerase chain reaction, is located as a slight signal in the proximal long arm of the Y chromosome of the white-handed gibbon, hamadryas baboon and Japanese monkey and in the middle long arm of the Y chromosome of the siamang, while a faint signal and an intense signal were detected in the proximal long arm of the Y chromosome of the agile gibbon. These findings allow us to speculate that the gibbons might have evolved some structural differentiation in theTSPY gene. The first introns of theTSPY genes were sequenced and compared. One hundred thirty-seven of 606 sites were found to be variable, and 10 deletions/insertions were noted among these gibbons, two species of Old World monkeys and human. Sequence similarity ranged from 81.7% between humans and hamadryas baboons to 98.7% between Japanese monkeys and hamadryas baboons. These sequences may be of great use in future studies for resolving the phylogeny of gibbons and Old World monkeys.accepted for publication by H.C. Macgregor     

Acquisition of oral phencyclidine (PCP) self-administration in rhesus monkeys: effects of dose and an alternative non-drug reinforcer

 The effects of drug dose and a non-drug alternative reinforcer on acquisition of oral PCP self-administration in rhesus monkeys were examined. Acquisition was studied using three groups of monkeys (seven subjects per group). One group received a low PCP dose (0.0375 mg/delivery) and the other two received a high PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to a saccharin solution (0.03% w/v) and water during the intersession (17.5-h) period. Food non-restricted monkeys were initially given access to water under a fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced with PCP during the session. The monkeys were then reduced to 85% of their free-feeding body weights and fed before the session, and the FR value was increased from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP were available under concurrent FR 8 schedules. At this final step of the procedure, acquisition of PCP self-administration was considered to occur if PCP intake consistently exceeded water intake. When all three groups were given concurrent access to PCP and water, PCP intake was greater than water intake only in the group of monkeys receiving the high PCP dose. PCP intake increased when water replaced saccharin during intersession in the high PCP dose group. Within-group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group given access to the high PCP dose while only 42.8% acquired in the other two groups. These data suggest that drug dose and presence of alternative non-drug reinforcers affect acquisition of drug self administration in non-human primates. Received: 14 May 1997 / Final version: 15 December 1997     

Serum interleukin-6 levels as an indicator of acute rejection after liver transplantation in cynomologous monkeys

This study was designed to evaluate whether the sequential monitoring of serum interleukin-6 levels (SIL-6) could be helpful for diagnosing the occurrence of hepatic allograft rejection. An SIL-6 post-transplant study was conducted on nine cynomolgus monkeys which had undergone orthotopic hepatic allotransplantation, six of which were treated with FK-506 (a new immunosuppressant agent isolated fromStreptomyces tsukubaensis) and three of which were not. All the nontreated animals showed biochemical abnormalities from days 5–6, characterized by a marked elevation of serum alkaline phosphatase levels, and they eventually died on days 8, 12, and 63 (group I). Acute cellular rejection was confirmed by histological study of the hepatic grafts taken at autopsy or biopsy. On the other hand, four of the treated animals (group IIa) survived more than 30 days. Biochemical examination of this group showed no abnormal signs apart from a slight elevation of alkaline phosphatase (<2000 IU/l). Histological examination carried out around 30 days after transplantation revealed a transient infiltration of polynuclear cells into Glisson's area, with the portal vein and bile duct remaining intact. The remaining two animals (group IIb) died of dehydration and arterial thrombosis on days 5 and 7, respectively. A kinetic study of SIL-6 conducted during the first 2 weeks showed quite different patterns among the three groups. All recipients in group I demonstrated two peaks following grafting on days 1 and 3 or 4, the second peak of above 2.0 U/ml preceding biochemical abnormalities by 2 to 3 days. Conversely, the recipients in group IIa showed a single peak of SIL-6 on day 1, followed by a decrease to less than 2.0 U/ml. Group IIb characteristically showed a high level of SIL-6 on day 1, after which the value remained over 2.0 U/ml. In conclusion, the monitoring of SIL-6 proved useful for detecting the acute rejection of hepatic allografts, the recipients with rejected grafts displaying two peaks of SIL-6 after grafting. The first increment was observed on day 1, which might reflect the stress of the surgical procedure, while the second transient increment of SIL-6, observed on day 3 or 4, might suggest acute hepatic rejection, preceding biochemical abnormalities by 2 to 3 days.     

Establishing and maintaining clinically healthy gingivae in Rhesus monkeys

The aim of the present investigation was to determine a method and a minimal frequency of plaque removal for the establishment and maintenance of clinically healthy gingivae in Rhesus monkeys. Six adult, male monkeys were used and divided into three groups. In each group different methods were used for plaque removal. Frequencies of plaque removal of one, two and three times per week for consecutive weeks were tested. The results showed that gingival health could be established and maintained with any of the methods used (toothbrushing and interdental flossing: toothbrushing and a 3-min application of 2% chlorhexidine gluconate) but only when plaque was removed 3 times a week. This frequency of plaque removal sessions is discussed in relation to the necessity for sedation of the animals with possible adverse side effects.