Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys

Vaccine-induced cellular immunity controls virus replication in simian immunodeficiency virus (SIV)-infected monkeys only transiently, leading to the question of whether such vaccines for AIDS will be effective. We immunized monkeys with plasmid DNA and replication-defective adenoviral vectors encoding SIV proteins and then challenged them with pathogenic SIV. Although these monkeys demonstrated a reduction in viremia restricted to the early phase of SIV infection, they showed a prolonged survival. This survival was associated with preserved central memory CD4+ T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans.     

Electrocortical correlates of stimulus response and reinforcement

Three patterns of electrical response were identified in the occipital cortex of rhesus monkeys making a differential discrimination: an input pattern that identifies which stimulus has been displayed; a reinforcement pattern that indicates whether the outcome of the differential response was rewarded or in error; and an intention pattern that occurs prior to the response and predicts which response the monkey is about to make. Neither the reinforcement nor the intention pattern is present while the monkeys perform at chance; at this time, only the differences due to input can be distinguished. These results suggest that more than simple input transmission is occurring in the primary visual mechanism. The influence of the experience of the organism is apparently encoded in the averaged electrical potentials recorded from the striate cortex.     

Deafferentation in monkeys: effect on conditioned grasp response

A preliminary technique was developed for conditioning grasp response in monkeys, for use in studying the effect of damage to the central nervous system on skilled movement. That subjects were able to learn this response with a deafferented hand, in the absence of vision, indicated that purposive movements of the distal musculature are less under the control of peripheral feedback than had been generally believed.     

Monkeys reared in isolation with pictures as visual input: evidence for an innate releasing mechanism

Monkeys reared in isolation from birth to 9 months received varied visual input solely from colored slides of monkeys in various activities and from nonmonkey pictures. Exploration, play, vocalization, and disturbance occurred most frequently with pictures of monkeys threatening and pictures of infants.From 2.5 to 4 months threat pictures yielded a high frequency of disturbance.Lever-touching to turn threat pictures on was very low during this period. Pictures of infants and of threat thus appear to have prepotent general activating properties, while pictures of threat appear to release a developmentally determined, inborn fear response.     

Visual cortex neurons: response to stimuli during rapid eye movements

While awake, unanesthetized monkeys held their eyes stationary, a motionless or slowly moving stimulus falling on the receptive field of striate cortex neurons produced an excitatory response. When a rapid eye movement was made across the same stimulus, many of these neurons continued to give an excitatory response. But the discharge of other neurons was unchanged or was suppressed during the eye movement.     

Copper on intrauterine devices stimulates leukocyte exudation

Metallic copper in the uterine or abdominal cavities of rats or monkeys stimulates an impressive local exudation of polymorphonuclear leukocytes. This cellular response to copper persists for at least 7 months, without significant local tissue damage or detectable systemic effects on the test animal. This finding provides a possible explanation for the capacity of copper to increase impressively the antifertility effect of polyethylene intrauterine contraceptive devices.     

Visual adaptation in monkey cones: recordings of late receptor potentials

The retinal cones of cynomolgus macaque monkeys show marked amounts of adaptation when the receptor potential is elicited by brief incremental stimuli presented against steady backgrounds of increasing intensity. The results can be accounted for by mechanisms of response compression, modified by the effects of photopigment bleaching, which together set the gain of the system at each background level, while also making the response nearly linear over a significant range of intensities above and below that of each adapting stimulus.     

Effect of deafferentation on a conditioned avoidance response

To determine whether peripheral afferent pathways could be bypassed in the performance of purposive movement, a group of monkeys was trained to avoid shock by flexing a forelimb in response to an auditory stimulus. The dorsal roots of the responding limb were then sectioned. Postoperatively it was found that the affected limb could be reconditioned.     

Electronarcosis and evoked cortical responses

Evoked response data and electrocorticograms were recorded in macaque monkeys under the influence of electronarcosis currents sufficient to render the animals unresponsive to peripheral nerve stimulation. The data were obtained from chronically implanted electrodes in the sensory cortex as well as depth electrodes directed to thalamic and reticular loci. At the levels of current used, the amplitude characteristics of the evoked response data were not appreciably modified.     

Patterns of corticosteroid and pepsinogen change related to emotional stress in the monkey

In association with conditioned avoidance sessions of 72 hours' duration, monkeys showed a response pattern characterized by increased levels of 17-hydroxy-corticosteroids and decreased levels of pepsinogen during the stress period, with a marked and prolonged elevation of pepsinogen levels occurring during the recovery period.     

Motor cortical encoding of serial order in a context-recall task

The neural encoding of serial order was studied in the motor cortex of monkeys performing a context-recall memory scanning task. Up to five visual stimuli were presented successively on a circle (list presentation phase), and then one of them (test stimulus) changed color; the monkeys had to make a single motor response toward the stimulus that immediately followed the test stimulus in the list. Correct performance in this task depends on memorization of the serial order of the stimuli during their presentation. It was found that changes in neural activity during the list presentation phase reflected the serial order of the stimuli; the effect on cell activity of the serial order of stimuli during their presentation was at least as strong as the effect of motor direction on cell activity during the execution of the motor response. This establishes the serial order of stimuli in a motor task as an important determinant of motor cortical activity during stimulus presentation and in the absence of changes in peripheral motor events, in contrast to the commonly held view of the motor cortex as just an "upper motor neuron."     

Maintenance of responding by fixed-interval schedule of electric shock presentation in squirrel monkeys

After stabilization of response rates engendered by a free-operant avoidance contingency, the lever-pressing of two squirrel monkeys was maintained for several months by a fixed-interval schedule of electric shock presentation. Initially, response-contingent shocks produced substantial increases in response rates. Continued exposure to the schedule resulted in a reduced overall rate accompanied by a change in the temporal patterning of responses. There was a pause in responding after most shock deliveries; the rate of responding then increased during the interval to reach a terminal value preceding shock presentation. Omission of shocks for part of the daily session led to higher rates of responding; the reintroduction of response-contingent shocks produced a lower overall rate and reinstated the temporal patterning of responding characteristic of the fixed-interval schedule.     

Prolonged color blindness induced by intense spectral lights in rhesus monkeys

Prolonged exposure of rhesus monkeys to intense blue light produces long-term changes which are consistent with loss of response of those cones that contain a photopigment with peak absorption at 445 nanometers. The 90 percent reduction of spectral sensitivity in the blue region has lasted more than 5 months. Reduced sensitivity to long wavelengths is produced by adaptation to light of 520 nanometers. This reduced sensitivity, which lasts no more than 30 days, is attributed to a temporary loss of response of the cones containing a photopigment with peak absorption at 535 nanometers.     

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease

Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.     

Orality, preference behavior, and reinforcement value of nonfood object in monkeys with orbital frontal lesions

Monkeys with orbital frontal ablation, compared with sham-operated controls, showed enhancement of oral tendencies toward nonfood items. Further, unlike the controls, they persistently performed an instrumental response for one of these nonfood items. On the other hand, the lesioned monkeys did not show altered preferences for food versus nonfood items. These findings suggest that reinforcement value and preferential ordering are dissociated by orbital frontal ablation.     

Superior colliculus cell responses related to eye movements in awake monkeys

Single cell responses were recorded from the superior colliculus of awake monkeys trained to move their eyes. A class of cells that discharged before eye movements was found in the intermediate and deep layers of the colliculus. The response of the cells was most vigorous before saccadic eye movements within a particular range of directions. These cells had no visual receptive fields, and visually guided eye movements were not necessary for their discharge, since they responded in total darkness before spontaneous eye movements and vestibular nystagmus.     

A neural mechanism for working and recognition memory in inferior temporal cortex

Inferior temporal (IT) cortex is critical for visual memory, but it is not known how IT neurons retain memories while new information is streaming into the visual system. Single neurons were therefore recorded from IT cortex of two rhesus monkeys performing tasks that required them to hold items in memory while concurrently viewing other items. The neuronal response to an incoming visual stimulus was attenuated if it matched a stimulus actively held in working memory, even when several other stimuli intervened. The neuronal response to novel stimuli declined as the stimuli became familiar to the animal. IT neurons appear to function as adaptive mnemonic "filters" that preferentially pass information about new, unexpected, or not recently seen stimuli.     

Discharge of frontal eye field neurons during eye movements in unanesthetized monkeys

Single unit activity was recorded from the frontal eye fields (area 8) in unanesthetized monkeys seated in a primate chair with the head restrained. The frontal eye field units were identified by antidromic response to stimulation of the cerebral peduncle. The findings indicate that most of the neurons discharge only after initiation of eye movements. These cells showed steady discharge when the eyes were immobile and oriented in a specific direction.     

Encoding of spatial location by posterior parietal neurons

The cortex of the inferior parietal lobule in primates is important for spatial perception and spatially oriented behavior. Recordings of single neurons in this area in behaving monkeys showed that the visual sensitivity of the retinotopic receptive fields changes systematically with the angle of gaze. The activity of many of the neurons can be largely described by the product of a gain factor that is a function of the eye position and the response profile of the visual receptive field. This operation produces an eye position-dependent tuning for locations in head-centered coordinate space.     

Nalorphine: increased sensitivity of monkeys formerly dependent on morphine

Three rhesus monkeys Macaca mulatta, formerly dependent on morphine, had increased sensitivity to nalorphine's effect of suppressing operant responding for food, as compared with two monkeys with no history of morphine exposure. Within the dose range employed, nalorphine injections produced emesis, salivation, and hyperirritability in formerly morphine-dependent monkeys but not in controls.