Distribution of skeletofusimotor axons in lumbrical muscles of the monkey

Summary The nerve supply to 25 poles of muscle spindles in the monkey was reconstructed by light microscopy of serial 1-m thick transverse sections of lumbrical muscles. Twenty of 60 motor axons that supplied the spindle poles were identified as skeletofusimotor (). Twenty-eight percent of the spindle poles were innervated by axons, in addition to axons. Every -innervated spindle pole transected an endplate zone of extrafusal muscle. Most axons coinnervated extrafusal fibers rich in mitochondria and the nuclear bag₁ or nuclear chain intrafusal fibers. All but two axons innervated one type of intrafusal fiber only. The intramuscular organization of motor system in lumbrical muscles of the monkey was similar to that of the cat tenuissimus muscle. The function of -innervated spindles may be preferentially to monitor mechanical disturbances arising from the activity of extrafusal muscle units with which they share motor innervation.     

Synthesis and evaluation of [11C]FR194921 as a nonxanthine-type PET tracer for adenosine A1 receptors in the brain

This report describes the synthesis of [¹¹C]2-(1-methyl-4-piperidinyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone ([¹¹C]FR194921), a highly selective, nonxanthine-type adenosine A₁ receptor antagonist, used in brain imaging in rats and conscious monkeys as a potential novel PET tracer. [¹¹C]FR194921 was successfully synthesized in 19 min after [¹¹C]CH₃I formation. The radiochemical yield was 38±3%; and radioactivity was 4.1±0.4 GBq, calculated from end of synthesis; radiochemical purity was higher than 99%; and the specific radioactivity was 25.0±8.1 GBq μmol⁻¹ (n=5). In a rat experiment, the distribution of [¹¹C]FR194921 was higher in the hippocampus, striatum and cerebellum regions. This accumulation was significantly decreased by approximately 50% by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A₁ receptor antagonist, which indicated specific binding of the radioligand to adenosine A₁ receptors. In conscious monkey PET experiments, [¹¹C]FR194921 accumulated in several regions of the brain, especially in the occipital cortex, thalamus and striatum. These results suggest that [¹¹C]FR194921 can be used as an agent for imaging adenosine A₁ receptors in vivo by positron emission tomography (PET).     

Effects of dopamine-receptor blockade on self-stimulation in the monkey

In a dose-response experiment it was shown that intraperitoneal injections of 0.062 mg/kg, and 0.1 mg/kg of the dopamine-receptor blocking agent and neuroleptic spiroperidol severely attenuate self-stimulation in the orbitofrontal cortex, hypothalamus, and in the region of the locus coeruleus, in the rhesus monkey and in the squirrel monkey. In the rhesus monkey intracranial injections of 6 μg of spiroperidol bilaterally into the nucleus accumbens or the hypothalamus attenuated self-stimulation of the amygdala, and injections into the orbitofrontal cortex attenuated self-stimulation of the amygdala and lateral hypothalamus. Self-stimulation at other sites tested (including the region of the locus coeruleus) was much less affected by the injections, and injections into the region of the locus coeruleus were ineffective. These results together with other control experiments suggest that spiroperidol can attenuate self-stimulation in the monkey independently of any motor impairment or sedation produced, and that dopamine receptors in particular brain regions are involved in self-stimulation of particular brain sites.     

Morphological studies about the efficiency of laser beams upon the structures of the angle of the anterior chamber

Working at a power density above optical breakdown threshold, irradiation effects upon the angle of the anterior chamber of the Macaca speciosa monkey by a Nd glass Q-switched laser, have been analysed with scanning electron microscopy.Two different damage effects can be identified: openings of Schlemm's canal and the creation of a cyclodialysis, that is opening the uveoscleral outflow routes; the latter may be a more effective one than the former. Also a third mechanism, namely a structural alteration of the trabecular meshwork, at the molecular level by laser action, has been inferred. The physical effects leading to optically induced mechanical damage are discussed. Applicability of such effects upon the morphological findings described here, is limited and to a greater part speculative. A better definition of the physical parameters, required for optimal therapeutical damage effects in the treatment of the wide angle glaucoma may be obtained by trial and error methods, which are guided by the results of electron microscopical analyses of samples obtained from in vivo and in vitro experiments.Work supported by the Swiss National Science Foundation, the Commission for the Promotion of Scientific Research, and the ASUAG.     

Dissociation of hemi-spatial and hemi-motor impairments in a unilateral primate model of Parkinson's disease

Monkeys with unilateral lesions of nigrostriatal dopamine projections were tested on a series of spatial tasks. One task, in which monkeys were required to use one or the other arm to retrieve food rewards from different positions, allowed separate assessment of the use of each arm in each hemi-space in order to distinguish hemi-spatial and hemi-motor impairments. The lesioned monkeys exhibited a persistent neglect of contralesional space when using either arm which could be dissociated from a motor impairment in the contralesional arm alone. Another task allowed free use of either arm across peri-personal space and demonstrated an ipsilesional bias in the monkeys’ self-determined attention (orientation) to a task which they were trying to perform. It is argued that the tendency for monkeys with this lesion to rotate ipsilesionally is due to an ipsilesional deviation of the ‘centre of interest’ (determined by telencephalic circuitry) relative to ‘straight ahead’ (determined by brainstem circuitry). The dopamine projections may contribute to cortico-subcortical circuits which determine the spatial layout of mental representation, attention and intention. The results in this primate model of unilateral Parkinson’s disease (PD) support the view that patients with left-sided Parkinsonian symptoms exhibit a unilateral deficit in spatial mental representation as well as their well-recognised motor symptoms. Patients with bilateral Parkinson’s symptoms may exhibit bilateral deficits in mental representation.     

Comparison of performance on memory-guided saccade and delayed spatial match-to-sample tasks in monkeys

To investigate the sources of spatial error in memory-guided saccades (MGS), we have trained monkeys on two different tasks: a MGS task and a delayed spatial match-to-sample (MTS) task. We first tested the effect of introducing a post-saccadic visual feedback on the accuracy of MGS. We found that visual feedback had a pronounced effect on the systematic saccade error, but less of an effect on the variable error. Visual feedback can improve the accuracy of saccadic eye movements over several days, while feedback removal can decrease accuracy in a reversible way. These effects also depend both on target eccentricity and the duration of the memory delay. To test whether saccade error is due to the accuracy of spatial memory storage or arises downstream from that memory, we measured behavioral performance on a spatial MTS task both before and after training with visual feedback. The results showed no significant difference in performance of the MTS task before and after feedback training despite significant changes in MGS accuracy. The results suggest that the accuracy of spatial memory is not the source of the systematic errors that accompany MGS.     

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement target, neurons nevertheless encode stimulus location. This observation could support the idea that these neurons always encode stimulus location, regardless of its relevance to an instrumentally conditioned behavior. Past studies, however, leave open the possibility that activity observed during one operant task might reflect the contingencies of a different task, performed at different times. To test these alternatives, we examined the activity of DMF and PF neurons in two rhesus monkeys conditioned to perform an operant eye-movement task in which only the color and shape of visual stimuli served as salient discriminative features. Each of eight stimuli was associated with a response to a different eye-movement target. The location of these stimuli varied from trial to trial but was of no behavioral relevance, and the monkeys did not perform any operant task in which stimulus location controlled behavior. A substantial minority of neurons in both DMF and PF nevertheless encoded stimulus location, which indicates that this property does not depend on its relevance in an instrumentally conditioned behavior. Electronic Publication     

Colour-related oscillations in the striate cortex of awake monkeys: "reverse" observations

Gamma oscillations of 30–70 Hz in local electroencephalograms (EEGs) were observed in primary visual cortex (V1) of monkeys when they viewed coloured stimuli under conditions which were not part of a training paradigm. No oscillatory modulations were detected in simultaneously recorded spike trains, although the latter responded to the stimuli. The oscillations had much longer latencies than the spike responses. Proceeding in a "reverse" manner, the oscillations were taken as primary elements of the analyses, and relationships to the accompanying behaviour were sought. Besides colour stimulation, the oscillations were found to be related to a form of annoyance. Only two of four monkeys showed the phenomena. We conclude that the oscillations had a central origin. Electronic Publication     

Increased incidence of dyskinesias and other behavioral effects of re-exposure to neuroleptic treatment in social colonies of Cebus apella monkeys

RATIONALE: Typical neuroleptic medications are still administered to as many as 40% of patients receiving antipsychotic treatment in the US. Intermittent administration or interruption of long-term neuroleptic medication for schizophrenia may increase the incidence of human tardive dyskinesias, and similarly may produce increasingly marked motor side-effects, parkinsonism, and other behavioral pathologies in non-human primates. OBJECTIVES AND METHODS: Given these similarities, we addressed the issue of prolonged and intermittent typical neuroleptic treatment and dopaminergic function during a 5-year, multi-phase study with social colonies of Cebus apella monkeys. In the previously reported phase 1, we examined the effects of 48 weeks of exposure to, followed by withdrawal from, fluphenazine decanoate (FPZ). Phase 3 reported here examined the effects of 18 weeks of re-exposure to FPZ in these same monkeys, 91 weeks after discontinuation of their phase 1 FPZ treatment. RESULTS: Analysis of blood plasma FPZ indicated levels of 0.22+/-0.08 ng/ml for the six injections during the re-exposure period (n=54), comparable to the 0.24+/-0.07 ng/ml levels measured during our original treatment with this dose. Acute dyskinesias and dystonias increased by 300% upon re-exposure to FPZ; 15 of 18 FPZ-treated animals exhibited oral-buccal dyskinesias and all exhibited torticollis or retrocollis. Retreatment with FPZ was also associated with highly significant reductions in Self- and Environment-Directed Behavior and Directed Affiliation, effects similar to those seen during the original phase 1 FPZ treatment. Although FPZ re-treatment was associated with a significant reduction in Directed Aggression (an effect that was more robust than that observed during phase 1), in phase 3, we again observed an increase in Directed Aggression during early drug discontinuation when animals were in a stress-inducing situation. CONCLUSIONS: These results both support our phase 1 conclusion that typical neuroleptic medications may contribute to negative symptoms of schizophrenia and provide additional evidence for the possibility of increased aggression in stressful situations when medication is discontinued. Additionally, the results indicate that intermittent treatment with typical neuroleptics may dramatically increase the incidence of dystonias and dyskinesias.