Directional organization of eye movement and visual signals in the floccular lobe of the monkey cerebellum

The floccular lobe of the monkey is critical for the generation of visually-guided smooth eye movements. The present experiments reveal physiological correlates of the directional organization in the primate floccular lobe by examining the selectivity for direction of eye motion and visual stimulation in the firing of individual Purkinje cells (PCs) and mossy fibers. During tracking of sinusoidal target motion along different axes in the frontoparallel plane, PCs fell into two classes based on the axis that caused the largest modulation of simple-spike firing rate. For horizontal PCs, the response was maximal during horizontal eye movements, with increases in firing rate during pursuit toward the side of recording (ipsiversive). For vertical PCs, the response was maximal during eye movement along an axis just off pure vertical, with increases in firing rate during pursuit directed downward and slightly contraversive. During pursuit of target motion at constant velocity, PCs again fell into horizontal and vertical classes that matched the results from sinusoidal tracking. In addition, the directional tuning of the sustained eye velocity and transient visual components of the neural responses obtained during constant velocity tracking were very similar. PCs displayed very broad tuning approximating a cosine tuning curve; the mean half-maximum bandwidth of their tuning curves was 170–180 °. Other cerebellar elements, related purely to eye movement and presumed to be mossy fibers, exhibited tuning approximately 40 ° narrower than PCs and had best directions that clustered around the four cardinal directions. Our data indicate that the motion signals encoded by PCs in the monkey floccular lobe are segregated into channels that are consistent with a coordinate system defined by the vestibular apparatus and eye muscles. The differences between the tuning properties exhibited by PCs compared with mossy fibers indicate that a spatial transformation occurs within the floccular lobe.     

Interactions of Phenytoin and Phenobarbital in Terms of Order and Temporal Spacing of Administration in Monkeys

The present study investigated order and temporal spacing interactions of phenytoin and phenobarbital in terms of plasma levels during multiple dosing in monkeys. Phenytoin at a dose of 30 mg/kg and phenobarbital at a dose of 3 mg/kg were administered separately to 4 animals (control group) by nasogastric intubution daily for 10 days. In four subsequent 10-day periods the drugs were administered together in 4 other animals (interaction group) at different times of the day (immediately following one another, 1/2 hr apart, and 6 hr apart) and in a different order of administration (either phenobarbital first and phenytoin later, or the reverse). Blood samples were obtained on the 5th, 8th, and 10th day of each 10-day period. The plasma data indicated: (a) phenytoin is capable of autoinduction, (b) phenobarbital lowers the levels of phenytoin under the four methods of administration studied here, and (c) phenytoin can affect the levels of phenobarbital. The latter interaction is a function of order and temporal spacing of drug administration.     

牙周病常用实验动物牙体解剖、牙周组织学研究与评价

目的:为口腔牙周病研究中实验动物的选择、实验部位的确定及实验方法的应用提供解剖、组织学依据。方法:选择3种常用实验动物豚鼠、犬、猴的牙体、牙周组织,进行大体、X线及组织学观察。结果:豚鼠口裂小,实验一般仅限于切牙区,但该区的龈沟上皮有角化,对炎症反应可能产生影响;犬的牙间间隙宽,适合作人工牙周骨下袋模型,牙虽不患龋,但根管粗,可用于髓病、根尖周病研究;猴是理想的实验动物,但价格昂贵,使大规模实验受到限制。结论:豚鼠、犬、猴的牙、牙龈、牙槽嵴形态及组织学表现均与人有相似性,但各有特点,在科研工作中应根据具体需要和财力选择实验动物、实验部位和实验方法。     

The glycine/NMDA receptor antagonist HA-966 impairs visual recognition memory in rhesus monkeys

Recent studies have shown that strychnine-insensitive glycine binding sites positively modulate the N-methyl-d-aspartate (NMDA) subclass of glutamate receptors, which are important in neural pathways involved in cognitive function. We examined the effect of (±)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a highly specific antagonist of this glycine modulatory site on the NMDA receptor, on visual recognition memory in four rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared with that of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of HA-966 (0.1–10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose-dependently, starting at doses of 3.2 mg/kg; the memory deficit following the highest dose (10 mg/kg) was associated with prolonged response latencies. Similar impairments in recognition memory were observed following treatment with MK-801, though at much lower doses (3.2–32 μg/kg) than those at which HA-966 was effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10 μg/kg), each of which had no significant effect on performance when given alone, also failed to impair performance when given concurrently. Combined administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA-966 plus 32 μg/kg of MK-801), markedly impaired performance in an additive, not a synergistic, manner. From these results, we propose that the recognition memory impairment observed in our monkeys following HA-966 administration is via an action on the glycine modulatory site of the NMDA receptor complex.     

Behavior of luminance neurons in the pretectal olivary nucleus during the pupillary near response

In cats and monkeys, extrastriate visual areas that have been reported to be involved in the near triad of pupilloconstriction, convergence, and accommodation have well-defined projections to the pretectal olivary nucleus (PON), the retinorecipient pretectal nucleus mediating the pupillary light reflex in mammals. We have therefore used alert, behaving primates to investigate the possibility that PON neurons are involved in the pupillary near response in addition to the pupillary light reflex. Single-unit recording revealed that PON luminance neurons significantly increased their firing rate with increases in retinal illumination and the resultant pupilloconstriction. In contrast, their activity did not significantly increase during pupilloconstriction elicited by near viewing. Thus the behavior of PON luminance neurons is appropriate for their participation in the pupillary light reflex, but is inappropriate for any proposed role in the pupillary near response. This result strongly suggests that neurons in the primate PON are solely related to the pupillary light reflex and that the cortical projections to this pretectal nucleus are related to this reflex and do not play a role in the pupillary near response.     

Autoradiographic analysis of the distribution of vasoactive intestinal peptide binding sites in the vertebrate central nervous system: a phylogenetic study

The distribution of vasoactive intestinal peptide (VIP) binding sites in the brain of several vertebrate species was examined by in vitro autoradiography on slide-mounted sections. This study included fish, frog, snake, pigeon, rat, mouse, guinea pig, cat and monkey brain. A fully characterized, monoiodinated form of vasoactive intestinal peptide (M-¹²⁵I-VIP), which maintains the biological activity of the native peptide in the central nervous system (CNS), was used throughout the study. Among the lower vertebrate species, no significant specific binding was found in the fish brain, whereas in the frog and snake brain, specific VIP binding sites were observed, mainly in the telencephalon. In the pigeon brain, high densities of VIP binding sites were localized in the hyperstriatum, neostriatum, archistriatum, hippocampal area, dorsolateral cortical area and in the optic tectum. Ectostriatum and paleostriatum augmentatum displayed lower densities of specific binding. In mammals, the highest concentrations of VIP binding sites were observed in the rodent brain. In the rat, mouse and guinea pig brain, high densities were detected in the olfactory bulb, external layers of the cerebral cortex, dentate gyrus, midline thalamic nuclei, geniculate nuclei, some hypothalamic nuclei, superior colliculus coeruleus. Intermediate densities were found in amygdala, caudate-putamen, septum and nucleus accumbens, CA1–CA3 fields of the hippocampus and central gray. The cerebellum of these species presented high densities of VIP binding sites, with species to species differences in their localization. The non-specific binding was, however, increased in the rodent cerebellum. Lower densities of VIP binding sites were observed in the cat and monkey CNS. In these two species, the non-specific binding was considerably higher than in the lower mammals brain. In the cat and monkey brain, as in the lower mammals, the highest densities were revealed in the neocortex, dentate gyrus, thalamic nuclei and some midbrain structures including substantia nigra and locus coeruleus. In all the species studied, the white matter was never labeled with M-¹²⁵I-VIP. This study suggests that VIP binding sites appear relatively early in the evolution of the vertebrate CNS. The most important densities of specific VIP binding sites are observed in the pigeon and rodent brain, whereas the cat and monkey present a marked increase in non-specific binding. It is interesting to note that the distribution of VIP binding sites as revealed by autoradiography is quite conservative in terms of evolution and indicates an association, although non-exclusive, of VIP receptors with brain regions involved in the processing of specific sensory inputs.     

Calcium-binding proteins are concentrated in the CA2 field of the monkey hippocampus: a possible key to this region's resistance to epileptic damage

Summary Previous immunocytochemical studies have shown a heterogeneous distribution of parvalbumin (PA) and calbindin (CB) in the rat hippocampal formation. The results of the present study showed a heterogeneous distribution of PA and CB in primate Ammon's horn. The density and intensity of immunoreactivity for both of these calcium-binding proteins was greatest in CA2 as compared to CA1 and CA3. CB-immunoreactivity was localized to the cell bodies, dendrites, and axon initial segments of pyramidal cells whereas PA-immunostaining was found in the axon terminals, dendrites and cell bodies of interneurons that have features similar to GABAergic inhibitory neurons. Based on previous studies that have shown a protective role of calcium-binding proteins in neurons exposed to hyperstimulation, these results suggest that the resistance of CA2 pyramidal cells in temporal lobe epilepsy is due to the high concentration of CB and PA in this region of Ammon's horn.     

Choline acetyltransferase immunopositive neurons in the lateral septum

A small cluster of choline acetyltransferase (ChAT)-positive neurons was identified immunohistochemically in rat and monkey brain in the ventral portion of the lateral septal nucleus. These multipolar neurons were smaller and much less intensely staining than the medial septal nucleus ChAT-immunopositive group.     

恒河猴外周血pDC1/pDC2的形态学研究

目的 研究恒河猴外周血pDC1和pDC2的形态学特征。方法 采集健康、SIV阴性的恒河猴外周血，用Ficoll—Hypaque梯度离心法提取外周血单核细胞(PBMC)。利用与恒河猴有交叉反应的人单克隆抗体以及三色流式细胞仪分离pDC1和pDC2。新鲜分离和经CD40L培养的pDC1进行形态学观察。新鲜分离和经CD40L、rhIL—3和rhGM—CSF培养的pDC2进行形态学观察。结果 恒河猴外周血树突状细胞(DC)具有较大不规则偏心的细胞核，其细胞表面有大量典型的树突状突起。结论 本研究为pDC1和pDC2作为抗原递呈细胞(APC)在排斥反应中的免疫调整功能奠定基础。     

Upregulation of striatal D2 receptors in the MPTP-treated vervet monkey is reversed by grafts of fetal ventral mesencephalon: an autoradiographic study

Although neural transplantation holds promise as a treatment for Parkinson's disease, parkinsonian primates have generally exhibited inconsistent and incomplete recovery of motor functions following intrastriatal grafting of fetal ventral mesencephalon. One possible contributing factor to this variable response is lack of appropriate integration of donor neurons with host striatal circuitry with the result that there is insufficient dopamine release and postsynaptic dopamine receptor activation. This issue was examined by measuring the effect of transplanting fetal ventral mesencephalon to the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP) monkeys on striatal D2 receptor binding. One year after receiving MPTP, D2 receptor binding was upregulated in the dorsal and ventral striatum of African green monkeys. Grafting of fetal ventral mesencephalon to the dorsal striatum of MPTP-treated monkeys 9 months before sacrifice, eliminated the D2 receptor upregulation in dorsal, but not ventral, region. Dopamine concentration in dorsal striatum of grafted MPTP-treated monkeys was significantly higher than in that region of MPTP-treated non-grafted monkeys. In addition, dopamine concentration was significantly higher in dorsal compared to ventral striatum of grafted MPTP-treated monkeys. These data, in addition to those from a previous autoradiographic study on dopamine uptake site density in these monkeys, strongly supports the hypothesis that ectopically placed ventral mesencephalon not only produces, but maintains the release of sufficient levels of dopamine to restore postsynaptic dopamine transmission in regions influenced by graft-derived dopamine.