Spatio-temporal firing patterns in the frontal cortex of behaving monkeys

Recording the activity of several neurons in parallel in the frontal cortex of behaving monkeys reveals that firing times of neurons can maintain +/- 1 ms accuracy even after delays of over 400 ms. The accurate firing structures were associated with behavior. Neural networks that can sustain such accuracy can learn 'learn' to bind with each other and thus may serve as building blocks for cognitive processes.     

Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs

Cerebellar Purkinje cell responses to granule cell synaptic inputs were examined with a computer model including active dendritic conductances. Dendritic P-type Ca2+ channels amplified postsynaptic responses when the model was firing at a physiological rate. Small synchronous excitatory inputs applied distally on the large dendritic tree resulted in somatic responses of similar size to those generated by more proximal inputs. In contrast, in a passive model the somatic postsynaptic potentials to distal inputs were 76% smaller. The model predicts that the somatic firing response of Purkinje cells is relatively insensitive to the exact dendritic location of synaptic inputs. We describe a mechanism of Ca2+-mediated synaptic amplification, based on the subspiking threshold recruitment of P-type Ca2+ channels in the dendritic branches surrounding the input site.     

Comparison of ventral subicular and hippocampal neuron spatial firing patterns in complex and simplified environments.

Activity from ventral subicular and hippocampal CA1 neurons was recorded in rats exploring a 4-arm radial maze in which the local and distal cues could be manipulated. Cells from both regions exhibited place fields, although ventral subicular neurons had larger fields than hippocampal cells. Rotation of the local and distal cues in opposite directions produced movement of the place fields in either direction or a complete change in firing pattern. Simplifying the environment also produced changes in place field location. Despite similarities between regions, subiculum fields decreased in size whereas hippocampal fields increased in the simple environment. These findings suggest that subicular cells may receive converging input from several hippocampal neurons and code more complex configurations of the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic ibogaine treatment on cerebellar Purkinje cells in the rat

The present investigation assessed the chronic toxicity of ibogaine on cerebellar Purkinje cells in male Fischer 344 rats. A behaviorally active dose of ibogaine (10 mg/kg, i.p.) was administered to a group of six subjects every other day for 60 days while the control group received an equivalent volume of saline (1 ml/kg). Estimates of Purkinje cell number were determined using the optical dissector/fractionator technique. No significant differences in Purkinje cell number were observed between the ibogaine (243764[+/-32766]) and control groups (230813[+/-16670]).     

The growth of the dendritic trees of Purkinje cells in irradiated agranular cerebellar cortex

The heads of noenatal Wistar rats were irradiated with 200 rads daily from birth to the 10th day post-partum. Ten litters each containing 5 animals were killed at 30 days post-partum and their brains treated by the Golgi-Cox technique. The dendritic trees of 24 Purkinje cells were analysed using the quantitative technique of network analysis, and comparisons made between parameters obtained from 20 normal Purkinje cells. All dendritic trees in agranular irradiated cortex were markedly reduced in size (as indicated by total dendritic length and total number of segments) although mean path lengths were normal. Segment lengths were normal over proximal branches, but uniformly increased over distal branches. Abnormal appendages, called 'giant spines' were observed on many dendrites. They were often some 10 mum in length and their presence effectively reduced segment lengths, increased the frequency of trichotomy and deviated growth from the normal random terminal pattern so that long collateral branching topologies were formed. Nevertheless, trichotomy was uniformly reduced in those trees without 'giant spines' and the distribution of branching patterns suggested that growth had proceeded by random terminal dichotomy. These results demonstrate that the development of dendritic trees is retarded in the agranular irradiated cerebellum, where synaptogenesis is very greatly reduced below normal. The quantitative changes in segment lengths, size of trees, and trichotomy accord with those predicted by the filopodial synaptogenic hypothesis of dendritic growth formulated by Vaughn et al. 99, whilst the results of the topological analysis suggest that branching is established by a degree of non-random interaction between growing dendrites and their substrate. 'Claw-like' dendritic complexes within some Purkinje cell trees may have been induced by aberrent fibre bundles of few surviving granule cells.     

IP3-activated calcium-permeable channels in the inside-out patches of cultured cerebellar Purkinje cells

Inositol-1,4,5-trisphosphate (IP3)-activated calcium-permeable channels were recorded from inside-out patches of cultured cerebellar Purkinje cells. When 2-5 microM of IP3 was applied to the internal surface of the inside-out patches, inward Ba2+ currents were activated within 10 sec following the application in 11 out of 24 patches. In the presence of heparin (100 micrograms/ml), activation of Ba2+ currents by IP3 was inhibited. Unitary currents with different amplitudes and kinetics were observed; small and large unitary currents, and rapid fluctuations with various amplitudes. The small unitary currents (single channel conductance; 5.6 pS) were most frequent. Addition of inositol 1,3,4-trisphosphate (2-5 microM) slightly activated Ba2+ currents in 2 out of 10 patches, but the amount of the increment was much smaller than that produced by IP3. These results suggest a possibility that IP3 directly activates Ca(2+)-permeable channels in the plasma membrane of cerebellar Purkinje cells.     

Differential expression of glutamate decarboxylase messenger RNA in cerebellar Purkinje cells and deep cerebellar nuclei of the genetically dystonic rat

The genetically dystonic rat exhibits a motor syndrome that closely resembles the human disease, generalized idiopathic dystonia. Although in humans dystonia is often the result of pathology in the basal ganglia, previous studies have revealed electrophysiological abnormalities and alterations in glutamate decarboxylase, the synthetic enzyme for GABA, in the cerebellum of dystonic rats. In this study, we further characterized the alterations in cerebellar GABAergic transmission in these mutants by examining the expression of the messenger RNA encoding glutamate decarboxylase (67000 mol. wt) with in situ hybridization histochemistry at the single cell level in Purkinje cells and neurons of the deep cerebellar nuclei. Glutamate decarboxylase (67000 mol. wt) messenger RNA levels were increased in the Purkinje cells and decreased in the deep cerebellar nuclei of dystonic rats compared to control littermates, suggesting opposite changes in GABAergic transmission in Purkinje cells and in their target neurons in the deep cerebellar nuclei. In contrast, levels of glutamate decarboxylase (67000 mol. wt) messenger RNA in the pallidum, and of enkephalin messenger RNA in the striatum, were unaffected in dystonic rats. The data indicate that both the Purkinje cells and GABAergic neurons of the deep cerebellar nuclei are the site of significant functional abnormality in the dystonic rat.     

Angiographic patterns of splenic lesions following blunt trauma. An experimental study in monkeys

Splenic angiography was performed before and after graded blunt trauma to the spleen in 15 monkeys. In 9 of these, followup angiography could be performed in week or more later. Pronounced spasm of the splenic artery and leakage of contrast medium into the peritoneal cavity were found to imply a serious prognosis. Local reversible spasm of arterial branches can cause transient defects in parenchymal filling. Larger defects corresponding to hematoma, extravasation of contrast medium, and displacement of vessels may be compatible with good primary prognosis. If, however, these signs indicate that the lesion is of sufficient magnitude and has a peripheral location there is a risk that extensive bleeding will occur. So-called delayed ruptures never occurred in this study.     

Lipofuscin pigment in cerebellar Purkinje neurones and choroid plexus epithelial cells of macaque monkeys with Plasmodium knowlesi cerebral malaria: an electron microscopical observation

Experimental infection of rhesus monkeys (Macaca mulatta) with a virulent (W1) strain of Plasmodium knowlesi resulted in cerebral malaria. Electron microscopical examination of the brain revealed large numbers of intracytoplasmic lipofuscin pigment deposits in cerebellar Purkinje neurones and choroid plexus epithelium of the lateral ventricle. This lesion may be part of the nervous system response to ischaemic hypoxia.     

Different functional effect of Ro 15-4513 and Ro 19-4603 on synaptic responses of Purkinje cells in the rat cerebellar slice

The Sugiura operation has been reported to have low operative mortality, rebleeding, and encephalopathy rates when carried out in a predominantly nonalcoholic Japanese population with good liver function. A literature review of reports of the Sugiura procedure outside Japan reveals a high complication and mortality rate when it is used as an emergency procedure in patients with advanced liver disease, especially in those with alcoholic cirrhosis. Uncontrolled studies report results that differ little from the Japanese series when the operation is confined to good-risk patients in the elective situation. Our experience with the Sugiura operation supports its role in these circumstances, especially in patients with portal vein thrombosis and normal liver function. The only good prospective controlled trial has been carried out in patients with schistosomiasis and suggests that the Sugiura operation is far superior to total shunt and may have a slight advantage over the Warren shunt because of its low incidence of postoperative encephalopathy. More controlled trials are required to establish its role in good- to moderate-risk patients with alcoholic cirrhosis.     

Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline

The exopolysaccharide acetan, elaborated by Acetobacter xylinum, has been investigated. The polysaccharide and a heptasaccharide, obtained on enzymic hydrolysis, corresponding to the repeating unit were characterised by sugar and methylation analysis and by NMR spectroscopy and MS. It is concluded that the polysaccharide is composed of repeating units with the following structure. [formula: see text] The polysaccharide further contains approximately two O-acetyl groups per repeating unit, which have not been assigned, but it appears that they are on primary locations.     

Calbindin immunoreactivity in Purkinje cells of the bullfrog cerebellum during thyroxine-induced metamorphosis

Calbindin-immunoreactive Purkinje cells were identified in the cerebella of frog tadpoles that had been treated with thyroxine to accelerate metamorphosis. The dorsal part of the cerebellar plate contained the full complement of Purkinje cells which were all CaBP-immunoreactive, while in the ventral part of the cerebellum Purkinje cells acquired CaBP-immunoreactivity only after several days of thyroxine treatment. The ventral group of Purkinje cells was separated from the dorsal group by a distinct gap, which is the site of a shallow sulcus in adult frogs. Additionally, following thyroxine treatment, the numbers of CaBP-immunoreactive Purkinje cells in the ventral group were only half the numbers seen in frogs that metamorphosed spontaneously. We suggest that the variation in the CaBP-immunoreactivity of the dorsal and ventral groups of Purkinje cells, along with the gap in the Purkinje cell layer between the two groups, may be indicative of two distinct populations of Purkinje cells, with distinct patterns of generation, maturation, and perhaps, origin and connectivity, in the cerebellum of frogs.     

Decreased IGF-I gene expression during the apoptosis of Purkinje cells in pcd mice

The purpose of this study was to develop concepts that facilitate our understanding of why family caregivers of demented elderly persons can continue caregiving despite various difficulties of care. Twenty-six Japanese daughter or daughter-in-law caregivers of elderly parents with dementia who lived at home or in long-term care facilities were recruited through various senior service organizations in Japan. The caregivers underwent unstructured interviews, and the interview data were analyzed using the constant comparative method. Three categories emerged as reasons for care continuation: value of care, maintainers of value, and reinforcers of care continuation. Value of care came from societal norms and attachment, and was the basis of caregivers' motivation to continue care. Several maintainers of value and reinforcers of care continuation also emerged from the analysis. The contents and some longitudinal changes in these categories were explained. The findings highlight the need to assess these categories separately in order to develop appropriate interventions and they have implications for future research and policy development.     

Monoclonal antibodies reveal expression of the CGRP receptor in Purkinje cells, interneurons and astrocytes of rat cerebellar cortex

The molecular layer of adult rat cerebellum displays high levels of calcitonin gene-related peptide (CGRP) receptors, but the cellular location of the receptor remains unidentified. In an attempt to reveal the expression sites of these receptors, monoclonal antibodies raised against purified CGRP receptors from porcine cerebellar membranes were used in double-immunofluorescence experiments combined with confocal microscopy. PEP-19, a marker that is highly enriched in Purkinje cells (Pc), revealed that CGRP receptors are located in Pc cytoplasm and dendrites, where they label small puncta sometimes arranged in a row along the course of the dendrite itself. CGRP receptors were also located in inhibitory interneurons. Furthermore, as shown by double-labeling experiments with GFAP, CGRP receptor-IR labeled Golgi epithelial cells and their radial fibers (Bergmann fibers), as well as astrocytic processes encircling Pc somata. The simultaneous presence of CGRP receptors in Purkinje cells and in the glial cells that heavily enshroud Purkinje cells allows us to hypothesize that these receptors may be involved in neuron-glia interactions influencing neuronal activity.     

Galanin messenger RNA during postnatal development of the rat brain: expression patterns in Purkinje cells differentiate anterior and posterior lobes of cerebellum

Following our initial mapping of preprogalanin messenger RNA in adult brain and its presence in a subpopulation of cerebellar Purkinje neurons [Ryan M. C. and Gundlach A. C. (1996) Neuroscience 70, 709-728], the present study examined the ontogenic expression of preprogalanin messenger RNA in the postnatal rat brain focussing on the Purkinje cells of the cerebellar cortex. Using in situ hybridization histochemistry, preprogalanin messenger RNA was detected in the developing forebrain and hindbrain from postnatal day 4 to day 60 (adult). On postnatal day 4 very light hybridization signal (labelling) was observed in cells of a number of nuclei including the central amygdaloid nucleus, the medial preoptic area, paraventricular nucleus and dorsomedial hypothalamic nucleus of the forebrain while lightly-labelled cells were detected in neurons of the nucleus of the solitary tract and locus coeruleus of the hindbrain. Hybridization signal was not apparent in other nuclei until later, with positively-labelled neurons first apparent in the dorsal cochlear nucleus at postnatal day 21. The abundance of preprogalanin messenger RNA-positive neurons and the intensity of the hybridization signal increased, in most regions, until postnatal day 28 when labelling resembled that of the mature rat. Preprogalanin messenger RNA was first detected in the cerebellum on postnatal day 10 only in Purkinje cells of lobule 10 of the posterior vermis and increased in distribution throughout Purkinje cell layers of the entire cerebellar cortex by postnatal day 13. The intensity of hybridization signal in Purkinje cells varied between lobules, with Purkinje cells in lobule 10 displaying a moderate to heavy degree of labelling, while lobules 6-9 and the more posterior lobules of the hemisphere including crus 2 of the ansiform lobule, the paramedian lobule and the copula pyramis, displayed only light labelling. The intensity of labelling in the anterior vermis and the remaining lobules of the hemisphere including crus 1 of the ansiform lobule, the simple lobule, the paraflocculus and the flocculus, was homogeneously weak. By postnatal day 21, Purkinje cell labelling reached maximum intensity in all lobules. Regional differences were still apparent, however, with labelling in the posterior vermis and hemisphere ranging from moderate to heavy, with only light to moderate labelling detected in the anterior vermis. The intensity of labelling in the posterior vermis and most lobules of the hemisphere was similar from postnatal day 21 to adulthood, while, in the anterior vermis, crus 1 of the ansiform lobule and the simple lobule, the intensity of hybridization decreased slightly by postnatal day 28 and was completely absent in Purkinje cells of the adult rat. Differential expression of preprogalanin messenger RNA in Purkinje cells of the developing rat cerebellum and transient expression in certain lobules suggests that galanin gene products may have a role in both the developing and mature rat brain and that galanin gene expression may represent a useful marker for differentiating the anterior and posterior cerebellar lobes.     

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation

1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration (gravity) components along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated in complete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these response components in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties that could be characterized as the low-frequency range of "translational" otolith-ocular reflexes; and 2) response vectors associated with an eye position modulation in phase with head position ("tilt" otolith-ocular reflexes). 4. The responses associated with two otolith-ocular vectors with pronounced dynamics consisted of horizontal eye movements evoked as a function of gravity along the interaural axis and vertical eye movements elicited as a function of gravity along the vertical head axis. Both responses were characterized by a slow-phase eye velocity sensitivity that increased three- to five-fold and large phase changes of approximately 100-180 degrees between 0.02 and 0.51 Hz. These dynamic properties could suggest nontraditional temporal processing in utriculoocular and sacculoocular pathways, possibly involving spatiotemporal otolith-ocular interactions. 5. The two otolith-ocular vectors associated with eye position responses in phase with head position (tilt otolith-ocular reflexes) consisted of torsional eye movements in response to gravity along the interaural axis, and vertical eye movements in response to gravity along the nasooccipital head axis. These otolith-ocular responses did not result from an otolithic effect on slow eye movements alone. Particularly at high frequencies (i.e., high speed rotations), saccades were responsible for most of the modulation of torsional and vertical eye position, which was relatively large (on average +/- 8-10 degrees/g) and remained independent of frequency. Such reflex dynamics can be simulated by a direct coupling of primary otolith afferent inputs to the oculomotor plant. (ABSTRACT TRUNCATED)     

Discharge properties of Purkinje cells in the oculomotor vermis during visually guided saccades in the macaque monkey

1. We previously described discharge properties of cerebellar output cells in the fastigial nucleus during ipsilateral and contralateral saccades. Fastigial cells exhibited unique responses depending on the direction of saccades and were involved in execution of accurate targeting saccades. Purkinje cells in the oculomotor vermis (lobules VIc and VII) are thought to modulate these discharges of fastigial cells. In this study we reexamine discharge properties of Purkinje cells on the basis of this hypothesis. 2. Initially we physiologically identified the right and left sides of the oculomotor vermis. Saccade-related discharges of 79 Purkinje cells were recorded from both sides of the vermis during visually guided saccades toward the sides ipsilateral and contralateral to the recording side in two trained macaque monkeys. To clarify the correlation of Purkinje cell discharge with burst activities in the fastigial nucleus during saccadic eye movements, we analyzed our data by employing methods used in the study of fastigial neurons. 3. Among the 79 cells, 56 (71%) showed burst discharges during saccades (saccadic burst cells). Of the 56 cells, 29 exhibited a peak of burst discharges in both the contralateral and ipsilateral directions (bidirectional cells). The remaining 27 saccadic burst cells showed a peak of burst discharges during either contralateral or ipsilateral saccades (unidirectional cells). Among the 79 cells, 14 (18%) exhibited a pause of discharges during contralateral saccades (pause cells). Among the 79 cells, 9 (11%) showed burst discharge during contralateral saccades followed by tonic discharge that was correlated with eye position (burst tonic cells). 4. The timing of bursts in bidirectional cells with respect to saccade onset was dependent on the direction of saccade. During ipsilateral saccades, Purkinje cells exhibited a long lead burst that built up gradually, peaked near the onset of the saccade, and terminated sharply near midsaccade. The mean lead time relative to saccade onset was 29.3 +/- 24.5 (SD) ms. During contralateral saccades, Purkinje cells exhibited a short lead/late burst that built up sharply, peaked near midsaccade, and terminated gradually after the end of the saccade. The mean lead time relative to saccade onset was 10.7 +/- 20.8 ms. The burst onset time during contralateral saccades and the burst offset time during ipsilateral saccades preceded the saccade offset time by about the same interval regardless of the saccade amplitude. 5. In pause cells the pause preceded saccade onset by 17.5 +/- 10.6 ms. The duration of the pause was not correlated with the duration of saccades. There was little trial-to-trial variability in the onset time of the pause with respect to the onset of saccades, whereas there was large trial-to-trial variability in the offset time of the pause with respect to the offset of saccades. In addition, the mean onset time of the pause for each cell had a relatively narrow distribution. 6. The burst lead time of burst tonic cells relative to saccade onset was 9.5 +/- 3.9 ms. The tonic discharge rate of burst tonic cells was a nonlinear function of eye position. The regression of each cell was fit to two lines. The regression coefficient ranged from 0.95 to 0.99 (mean = 0.97). 7. Axons of Purkinje cells in the oculomotor vermis are thought to project exclusively to saccadic burst cells in the fastigial oculomotor region (FOR), which is located in the caudal portion of the fastigial nucleus. Our previous studies indicated that FOR cells provide temporal signals for controlling targeting saccades. The present results suggest that Purkinje cells in the oculomotor vermis modify the temporal signals of FOR cells for saccades in different directions and amplitudes. The modification of FOR cell activity by Purkinje cells is thought to be essential for the function of the cerebellum in the control of saccadic eye movements.     

Spatial organization of proprioception in the cat spinocerebellum. Purkinje cell responses to passive foot rotation

This study examines the spinocerebellar locations of Purkinje cells that responded to passive foot rotations at the ankle joint in anaesthetized cats. Using a novel approach for mapping the locations of recorded cells from several animals onto an unfolded two-dimensional representation of the cortex, we found that cells distributed throughout the anterior-posterior extent of the spinocerebellar cortex, except in the most medial parts corresponding to zones a and b, were responsive to ankle joint rotation. The cell distributions revealed a clustering according to their response amplitudes, which showed evidence for both parasagittal and transverse banding.     

Arginine deprivation in KB cells. II. Characterization of the DNA synthesized during starvation

DNA synthesis in cells deprived of arginine was examined. Three lines of evidence indicated that tritiated thymidine ([3H]TdR) incorporation in arginine-starved cells was due to replicative rather than repair DNA synthesis. (a) When made in the presence of bromodeoxyuridine, the [3H]TdR-labeled DNA sedimented at hybrid density in isopycnic gradients. (b) As determined by the diphenylamine reaction, there was a 15% increase in the chemical amount of DNA per culture 30 h after arginine deprivation. (c) [3H]TdR incorporation was hydroxyurea-sensitive. Alkaline velocity sedimentation of the total DNA made during starvation revealed the existence of two distinct size classes: most of the DNA sedimented at a position analogous to that of control DNA, but 40% migrated one-third the distance of the bulk. After arginine restoration, these shorter pieces appeared to be chased into DNA of normal length; thus, one lesion in deprived cultures may cause an arrest in completion of DNA stretches to mature size. These findings, together with results of morphological studies of starved cells, suggest that changes induced by arginine deficiency effect the organization of nucleoproteins. These changes are reversible upon arginine restoration.     

Disruption of cerebellar cortical inhibition in the absence of learning promotes sensory-evoked eyeblink responses.

Theories of cerebellar learning propose that alterations in synaptic plasticity resulting in decreases in cerebellar cortical inhibition and increases in sensory activation of interpositus nuclei underlie the development of adaptively timed conditioned motor responses. The authors found that with concurrent pharmacological disconnection of the cerebellar cortex and intense sensory stimulation in the untrained rabbit, eyeblink responses were generated. Neither sensory stimulation nor disconnection alone generated significant eyeblink responses. These results are consistent with dual plasticity models of cerebellar learning and strongly support the general hypothesis that conditioned responses are the result of strengthening of preexisting connections in the nervous system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)