Afferents to the cerebellar flocculus in cat with special reference to pathways conveying vestibular, visual (optokinetic) and oculomotor signals

Summary Horseradish peroxidase (HRP) was injected into the cerebellar flocculus of 20 cats to determine: (a) the proportions of afferents from the various brain stem nuclei; (b) possible projections from the basilar pontine nuclei; and (c) sources of saccadic eye movement signals recorded from flocculus Purkinje cells. Results confirm earlier findings that the flocculus receives large numbers of mossy fibre afferents from the vestibular and perihypoglossal nuclei, bilaterally, and climbing fibres from the contralateral inferior olive (dorsal cap, ventrolateral outgrowth, medial accessory olive, ventral bend of principal olive). In addition, large numbers of HRP-labeled neurons have been identified within: (i) the basilar pontine nuclei, bilaterally, where they are distributed in columns in the dorsolateral, lateral, ventral medial and dorsomedial nuclei; (ii) the nucleus reticularis tegmenti pontis; (iii) several of the cranial motor nuclei, VI, VII, X (retrofacial n.), XI (n. ambiguus), and XII; (iv) the raphe magnus, pontis and obscurus; (v) the lateral reticular nucleus, pars subtrigeminalis.Finally, new information is presented which shows that large numbers of flocculus projecting neurons are located within the medial longitudinal fasciculus at two locations; one just rostral to the hypoglossal nucleus and another group extends 2–3 mm rostral to the abducens nucleus. These groups are bilateral, and have been termed, respectively, the caudal and intermediate interstitial nucleus of the medial longitudinal fasciculus. Both groups correspond in location to physiologically identified neurons in cat which fire in relation to saccadic eye movements. Their projection to the flocculus, in part, explains the saccadic discharge of Purkinje cells in the flocculus.     

Encoding of eye position in the goldfish horizontal oculomotor neural integrator

Monocular organization of the goldfish horizontal neural integrator was studied during spontaneous scanning saccadic and fixation behaviors. Analysis of neuronal firing rates revealed a population of ipsilateral (37%), conjugate (59%), and contralateral (4%) eye position neurons. When monocular optokinetic stimuli were employed to maximize disjunctive horizontal eye movements, the sampled population changed to 57, 39, and 4%. Monocular eye tracking could be elicited at different gain and phase with the integrator time constant independently modified for each eye by either centripetal (leak) or centrifugal (instability) drifting visual stimuli. Acute midline separation between the hindbrain oculomotor integrators did not affect either monocularity or time constant tuning, corroborating that left and right eye positions are independently encoded within each integrator. Together these findings suggest that the "ipsilateral" and "conjugate/contralateral" integrator neurons primarily target abducens motoneurons and internuclear neurons, respectively. The commissural pathway is proposed to select the conjugate/contralateral eye position neurons and act as a feedforward inhibition affecting null eye position, oculomotor range, and saccade pattern.     

Deficits of cortical oculomotor mechanisms in cerebellar atrophy patients

Commonly, the cerebellum is not associated with cortical components of saccadic eye movement programming. The present study investigates cerebellar effects on visually guided saccades in reflexive tasks (step, gap, overlap) and on internally driven saccades in intentional tasks (anti, memory, short memory sequences of four targets) in five patients with isolated cerebellar atrophy. The cerebellar dysfunction led to impairments in both reflexive and intentional saccades. Cerebellar atrophy patients showed an increase in the gain variability and an increase in the saccade latency. Furthermore, in the memory and anti task, suppression and pro-saccade errors were more frequent in the atrophy group compared to the control group. In the sequence task, patients had difficulties reproducing all four target locations in the order of the displayed sequence. The high variability of the saccade gain is a common observation in cerebellar atrophy patients and can be explained by the general variability present in the saccadic system. The increase in the saccade latency could be due to a cerebellar contribution to cortical processes related to fixation and target selection preceding the initiation of a saccade. Furthermore, the frequent occurrence of saccade errors in the memory and anti task suggests a cerebellar involvement in frontal inhibition of unwanted reflexive saccades. The impaired reproduction of saccade sequences in atrophy patients points to a deficit in short-term memory processes. Thus, this study provides further evidence that the cerebellum is involved in different cortical mechanisms related to the control of saccadic eye movements.     

The feline oculomotor nucleus: morphological subdivisions and projection to the cerebellar cortex and nuclei

Summary The cytoarchitecture of the feline oculomotor nucleus was examined in sections stained with thionin and neutral red. Five different subdivisions (caudal central, paramedian, ventral, dorsomedial and dorsolateral divisions) can be identified on each side of the midline. This observation is discussed, and our findings are compared to previous studies of the cytoarchitecture or central muscular representation of the oculomotor nucleus in which different subgroups have been distinguished. Implants or injections of the wheat germ agglutinin-horseradish peroxidase complex have revealed that all five subdivisions project to different parts of the cerebellar cortex and nuclei. Retrogradely labelled cells were found in the oculomotor nucleus in 18 cases following deposition of tracer in the fastigial and interposed nuclei and certain regions of the anterior, posterior and flocculonodular lobes. The projection is bilateral and appears to have its main termination in flocculus. It originates from small neurons, especially from those located along the dorsal border of the oculomotor nucleus.     

Spino-olivocerebellar pathways to the posterior lobe of the cat cerebellum

Summary Surface- and micro-electrode recordings were made from the left paramedian lobule of the cat cerebellum in order to investigate responses generated by stimulation of the superficial radial nerves. The existence was demonstrated of two climbing fibre (CF) paths from the forelimb, closely resembling two well-known paths terminating in the anterior lobe of the cerebellum — the dorsal funiculus spino-olivocerebellar path (DF-SOCP) and the lateral funiculus climbing fibre spinocerebellar path (LF-CF-SCP).Simultaneous recordings from the paramedian lobule and the anterior lobe showed that corresponding CF responses in the two areas had identical latencies, thresholds, stimulus/response relationships, recovery cycles and similar reactions to certain spinal cord and brain stem lesions. The characteristic fluctuations which occur in the amplitude and latency of CF responses in the anterior lobe were synchronous with similar fluctuations in the paramedian lobule. It was concluded that the DF-SOCP and the LF-CF-SCP reach both areas.Further recordings showed that the LF-CF-SCP terminates in a narrow zone of cortex which extends continuously from the intermediate anterior lobe across lobulus simplex and crus I onto the paramedian lobule. The DF-SOCP has a dual termination in the intermediate anterior lobe; one terminal zone was shown to extend from anterior lobe to paramedian lobule but the second (lateral) zone could not be traced behind lobulus simplex.Micro-electrode recordings from the right inferior olive showed cells projecting to the terminal zones of each of the two pathways. Their responses to nerve stimulation were compatible with their being relay cells on the DF-SOCP and the LF-CF-SCP.     

Compensation of oculomotor deficits in monkeys with neonatal cerebellar ablations

The oculomotor performance of 11 monkeys, who had various degrees of cerebellar ablation shortly after birth, is described in this study. Detailed numerical results were obtained on three of these adult macaques after extensive training of specific pursuit eye movements and fixation. The vestibular nuclei were kept intact. In the presence of the intracerebellar nuclei, quite extensive neonatal ablations of the cerebellar cortex leave the adult monkey without any discernible oculomotor deficits. If ablation also includes the nuclei on one side, compensation is never complete even several years later: while vestibulo-ocular and saccadic responses seem normal, there are deficits in pursuit and gaze holding performance. The residual deficits vary with the extent of the ablation and are comparable with the pattern exhibited by acute hemicerebellar ablations. Monkeys who had their cerebellum including the nuclei essentially completely removed just after birth, could pursue, albeit with limited velocity, and hold gaze, albeit in a limited zone. Their vestibulo-ocular responses seemed unaffected.     

Relative contributions of the cerebellar vermis and prefrontal lobe volumes on cognitive function across the adult lifespan

Recent research has revealed significant relationships between the vermian regions of the cerebellum and cognitive functions typically associated with prefrontal lobe function. These relationships are believed to be supported by anatomical connections between the distant brain regions. Recent evidence also suggests that age-related reductions in the posterior vermis are associated with age-related decline in frontal lobe cognitive functions, but these studies did not consider concomitant age-related atrophy of the prefrontal lobes. In the present study we addressed this issue by examining cognitive and structural MRI data obtained from 251 adults ranging in age from 18 to 79. Cognition was examined with a computerized cognitive battery and volumes of the cerebellar vermian regions and the prefrontal lobes were determined using quantitative morphometry. Results of the study revealed that both prefrontal and vermian volumes were smaller in older adults compared to younger adults, and both volumes correlated with cognitive performances in the older individuals. However, after controlling for prefrontal volume, the relationships between cognitive function and vermian volumes were eliminated, whereas prefrontal lobe volume remained significantly related to cognitive function after controlling for vermian volumes. These results suggest that while a reduction in cerebellar vermian volume does not significantly relate to normal age-related cognitive decline, prefrontal volume is significantly related to cognitive aging. Our results are consistent with the frontal aging hypothesis.     

The physiology of marriage: pathways to health

Marriage is the central relationship for most adults and has beneficial effects for health. At the same time, troubled marriages have negative health consequences. This review outlines the physiological pathways through which marital relationships influence health based on a stress/social support model. In addition, we review recent findings suggesting that unhappy marriages are associated with morbidity and mortality. We then turn to studies of marital interaction that include assessment of physiological pathways through which marital functioning influences health: the cardiovascular, endocrine, and immune systems. Across these studies, negative and hostile behaviors during marital conflict discussions are related to elevations in cardiovascular activity, alterations in hormones related to stress, and dysregulation of immune function. Using recent conceptualizations of the physiological impact of chronic stress, we illustrate how physiological changes associated with marital functioning in these studies have long-term implications for health outcomes. Finally, we discuss future implications of current research for understanding the relationships among marital functioning, physiology, and health.     

Cholinergic,GABAergic and excitatory amino acidic neurotransmission in the goldfish vagal lobe

Summary Some neurotransmitter systems operating in the goldfish vagal lobe, an hypertrophied gustatory center, have been studied by means of experimental (kainic acid injection and vagal rhizotomy), neurochemical and ultrastructural methods. The use of the neurotoxin, kainic acid, revealed the existence of cholinergic and GABAergic neurons in the vagal lobe. The results of histochemical observations and biochemical assays performed after rhizotomy of sensory and motor vagal roots, suggest that the motor neurons of the vagal motor layer are cholinergic. The same experiments also indicate that the primary gustatory afferents distributing to the sensory layer of the vagal lobe are, at least in part, cholinergic. By contrast, no decrease of excitatory amino acid uptake was demonstrated following the experimental lesions. GABA is likely to play an important role in the goldfish vagal lobe, particularly in the sensory layer, where the highest level of its synthetic enzyme, glutamate decarboxylase, is recorded. The significant decrease of glutamate decarboxylase in the sensory layer after vagal rhizotomy suggests that either GABAergic primary afferents reach the vagal lobe, or that deafferentation results in a decreased GABA synthesis in intrinsic GABAergic neurons.Supported by research grants of the Italian Ministry of Education     

Topography of the oculomotor area of the cerebellar vermis in macaques as determined by microstimulation

1. Oculomotor responses to microstimulation of the cerebellar vermis of macaque monkeys were investigated by using a magnetic search-coil method. 2. The oculomotor responses were conjugate eye movements with an ipsilateral horizontal component. Analyses of amplitude-velocity and amplitude-duration relationships revealed that the peak eye velocities and the durations of the responses were comparable to those of saccadic eye movements. 3. Systematic mapping with microstimulation disclosed that the region in the cerebellar vermis that yielded saccades with weak stimulus currents was confined to lobule VII in five monkeys but included a part of folium VIc in the other four monkeys. This region coincided with the distribution of the saccade-related neural activity observed in the present study and also corresponded to the vermal folia from which we recorded the burst mossy-fiber units and the oculomotor Purkinje cell activity. 4. The oculomotor vermis was defined as that region of the cerebellar vermis that met the following criteria: 1) saccades were evoked with low-intensity microstimulation (with currents less than 10 microA); 2) vigorous saccade-related neural activity was present; and 3) Purkinje cell discharges were modulated with eye movements. The oculomotor vermis was more circumscribed and located more posteriorly than the vermal cortex explored in previous microstimulation experiments on monkeys. 5. Microstimulation of the oculomotor vermis evoked more or less curved saccades in oblique directions. The horizontal and vertical components were not simultaneous in some saccades: the shorter component started later or ended earlier than the other component and their peak velocities were not always synchronous. 6. The amplitude of the saccade depended on stimulus parameters; microstimulation with 10-12 pulses within a period of approximately 20 ms (500-600 Hz) was shown to be optimal. When the pulses were applied to the white matter or to the granular layer, a stimulus current of 10 microA was sufficient to evoke saccades. When the molecular layer was stimulated, evoked saccades were smaller and frequently curved, and an increase in the stimulus current changed either the initial direction or the trajectory of the saccade. 7. When the stimulus current was carefully controlled and maintained near the threshold, the direction of the saccade evoked from the oculomotor vermis was topographically organized.(ABSTRACT TRUNCATED AT 400 WORDS)     

Visual and oculomotor function in optic chiasma-sectioned rabbits

Summary Anatomical and physiological findings indicate that the crossed optic fibres of the rabbit have a crucial role in binocular vision. In order to directly examine the visual functions of the uncrossed fibre system, a technique of sectioning the optic chiasma midsagitally was developed. Both normal and chiasma-sectioned rabbits were tested on a variety of visual discrimination tasks as well as such oculomotor control functions as the optokinetic and vestibulo-ocular reflexes. Following transection of all contralateral retinal projections, rabbits were found to retain the same visual capacity for detection of intensity and orientation differences as before the operation. There was, however, a complete loss of optokinetic reflexes and a 50% reduction of the vestibulo-ocular reflex both in the light and in the dark.     

Sagittal zonal organization of climbing fibre input to the cerebellar anterior lobe of the ferret

The organization of climbing fibre input to the cerebellar anterior lobe of the ferret was investigated in barbiturate-anaesthetized animals. Climbing fibre field potentials evoked on electrical stimulation of forelimb and hindlimb nerves were recorded at the cerebellar surface. Based on characteristic latencies of climbing fibre responses and their relative localization along the longitudinal axis of the folia, nine sagittally oriented zones could be distinguished and were tentatively named, from medial to lateral, A, X, B, C1, Cx, C2, C3, D1 and D2. Within the C1, C2 and C3 zones, climbing fibre input from the ipsilateral forelimb was found caudally and from the hindlimb rostrally, while the corresponding topographical representation in the B and D2 zones was medial to lateral. The X, Cx and D1 zones did not receive input from the hindlimb, while input from the forelimb to the A zone was weak. Overall, the sagittal zonal organization of climbing fibre input appears to conform with the compartmentalization of the ferret cerebellum based on the myeloarchitecture of corticonuclear fibres, although the X and Cx zones have not been previously identified. In terms of both general electrophysiological characteristics of input to different zones and intrazonal topographical representation, the organization of climbing fibre input to the ferret cerebellum seems to strongly resemble that in the cat. The findings thus provide evidence of cross-species generality of cerebellar sagittal organization. Received: 31 January 1997/Accepted: 30 April 1997     

Morphology and morphometry of the caudate lobe of the liver in two populations

The caudate lobe of the liver has portal blood supply and hepatic vein drainage independent of the remainder of the liver and may be differentially affected in liver pathologies. Ultrasonographic measurement of the caudate lobe can be used to generate hepatic indices that may indicate cirrhosis. This study investigated the relationship of metrics of the caudate lobe and other morphological features of human livers from a northwest Indian Punjabi population (n = 50) and a UK Caucasian population (n = 25), which may affect the calculation of hepatic indices. The width of the right lobe of the liver was significantly smaller, while the anteroposterior diameter of the caudate lobe and both Harbin’s Index and the Hess Index scores were significantly larger in NWI livers than in UKC livers. The Hess Index score, in particular, is much larger in the NWI population (265 %, p < 0.005). Two caudate lobe features were significantly different between the two populations—the shape of the caudate lobe and the development of the caudate process. This study shows significant population differences exist in several metrics and morphological features of the liver. These differences may affect the calculation of hepatic indices, resulting in a greater percentage of false positives of cirrhosis in the NWI population. Population-specific data are required to correctly determine normal ranges.