Impairments in working memory and decision-taking processes in monkeys in a model of Alzheimer’s disease

Studies were performed on two groups of animals (three monkeys in each). Monkeys of group I received unilateral intracerebroventricular injections of the neurotoxin p75-saporin (the ribosomal toxin saporin bound to monoclonal antibody to the p75NTR receptor), which elicits irreversible degradation of cholinergic neurons in the basal nuclei of Meynert, along with the enzyme dopamine--hydroxylase (DBH-saporin), which impairs the functioning of noradrenergic neurons in the locus ceruleus. Monkeys of group II received injections of sterile physiological saline (0.9% NaCl). Monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids, geometric figures with different colors, different spatial relationships between objects) and perform spatial selection. The characteristics of working memory were identified in delayed differentiation tasks in monkeys of both groups before and after injections. These studies provided the first evidence that the development of Alzheimers disease in rhesus macaques is characterized by a deficiency of working memory, this being based on impairment of two components of these processes. Impairment of the first in monkeys of group I was manifest in delayed visual differentiation as a significant decrease in correct responses. The extent of decreases depended on the duration of the delay and the type of visual information. Impairment of the second component, associated with decision-taking processes, was characterized by an increase in refusals to take decisions and was independent of the duration of delays and the type of visual information. Monkeys given injections of physiological saline showed no significant differences in these characteristics. The features of impairments in these memory components resulting from the development of Alzheimers disease demonstrate that the structural-functional organization of cholinergic and noradrenergic mechanisms responsible for sensory processing differ from those involved in decision-taking.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 9, pp. 1033–1045, September, 2003     

Oxidative Stress Level in Circulating Neutrophils Is Linked to Neurodegenerative Diseases

Alzheimers and Parkinsons diseases are the most common neurodegenerative conditions. Oxidative lesions are a hallmark of both diseases, but the respective roles of systemic and cerebral dysfunction are not elucidated. As circulating neutrophils are the most powerful sources of reactive oxygen species, we measured oxidative stress levels in resting neutrophils from 44 Alzheimers and Parkinsons disease patients and compared them to 40 healthy counterparts. Significantly increased oxidative stress levels were observed in patients groups, while control groups had very similar levels irrespective of age. One-third of the neurodegenerative patients presented with oxidative stress levels higher than those of any healthy donor. This increase was not due to an elevated production of reactive oxygen species during the neutrophil oxidative burst. Mitochondrial mass and activity were altered in neutrophils of the Parkinsonian group compared to controls, but not in those from Alzheimers disease group. To our knowledge, this is the first report linking oxidative stress and mitochondrial parameters in circulating neutrophils from neurodegenerative and normal donors. Our results indicate that oxidative stress levels in circulating neutrophils are of interest for further mechanistic studies of neurodegenerative diseases and might open the perspective of a diagnostic tool.     

The effect of central retinal lesions on optokinetic nystagmus in the monkey

Summary In alert monkeys (Macaca mulatta and fascicularis) the effect of central retinal lesions on fast optokinetic responses was investigated during high velocity optokinetic and visual-vestibular conflict stimulation. The fast component of the optokinetic response manifests itself as a rapid rise in the slow-phase eye velocity after light-on, during high velocity optokinetic stimulation; and a sudden drop in eye velocity after light-off. In contrast, the velocity storage component leads only to gradual changes in eye velocity during continuous optokinetic stimulation and after light-off (optokinetic after-nystagmus).Retinal lesions were placed by laser coagulation in and around the fovea. Responses of the normal and lesioned eye were compared. It was found that central lesions up to 12 deg (fovea diameter 6 deg) had only a negligible effect on fast optokinetic responses. With lesions of more than 25–30 deg diameter centered on the fovea definite fast responses could still be obtained, on average reduced to about 50% of the responses of the normal eye. Some monkeys showed initially no fast optokinetic responses and had, therefore, to be excluded from lesion experiments.The results demonstrate that fast optokinetic responses also can be obtained from extrafoveal areas, i.e. areas which are not generally involved in smooth pursuit eye movements. These results are discussed in relation to reports that the smooth pursuit eye movement system is also used to generate fast optokinetic responses.Supported by Swiss National Foundation for Scientific Research 3.343-2.78 and Deutsche Forschungsgemeinschaft, SFB 200 A2These experiments were performed at the Dept. of Neurology, University of Zürich. A preliminary report of this work was presented at the workshop on Physiological and pathological aspects of eye movements in Habay-la-Neuve (Belgium) and at the 8th Extraordinary Meeting of the Barany Society in Basel (Switzerland)     

Memory-guided saccades in Parkinson’s disease: long delays can improve performance

A recent study in control subjects suggested the existence of separate pathways for oculomotor spatial working memory tasks depending on whether the delay before movement execution is either short or long (>20 s). The long delay pathway might bypass brain areas commonly affected by Parkinsons disease (PD). This study aimed to assess spatial working memory in Parkinsons disease using short (3 s) and long (30 s) delays in a memory-guided saccade task. Fifteen mild-moderately affected PD subjects off-medication, and 15 age and sex-matched controls were tested (PD mean age 65.3; control 65.9). Subjects were tested in a darkened room using a horizontal LED bar to generate eye movements which were recorded using an infrared limbus tracker. Percentage error in amplitude of the primary saccade was analysed by repeated measures ANOVA. There was a significant interaction between the groups and their response to the short and long delay periods (P<0.02). PD subjects were more strongly impaired in the short delay than the long delay trials when compared with controls. Analysis of the percentage error in amplitude of the final eye position showed the same pattern but only in female subjects. This study provides the first evidence that the proposed parallel spatial memory pathway utilised in longer delay periods is relatively unimpaired in PD. In a broader sense, our results suggest there might be other alternative pathways to overcome deficits in functions impaired by PD.     

Formation of Supramolecular Aggregations of γ-Globulin as a Metal-Dependent Process

The presence of copper cations in the solution of human serum -globulin induced the formation of supramolecular forms of the protein. The intensity of this reaction increased with increasing copper concentration. The mechanisms of -globulin aggregate formation under normal conditions and the possible role of bivalent metal cations in the regulation of protein effector functions are discussed.__________Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 139, No. 2, pp. 185–187, February, 2005     

Statin treatment and a disease-specific pattern of β-amyloid peptides in Alzheimer’s disease

According to the amyloid cascade hypothesis, sporadic Alzheimers disease (AD) is caused by the production and aggregation of -amyloid (A), and the production of A has recently been linked to the metabolism of cholesterol. We have previously published clinical studies where the effect of statin treatment on A production has been investigated. No effect on A was found, which is in disagreement with cell and animal studies. In the present study we investigated the effect of statin treatment on a disease-specific pattern consisting of a C-terminally-truncated quintet of A peptides. Nineteen patients with AD were treated with simvastatin for 12 months and the quintet of A peptides were analysed in cerebrospinal fluid before and after treatment. Also included was a group of 15 untreated patients with AD. We found that the A peptide pattern at baseline was in agreement with earlier findings; however, we did not find any change in the A peptide pattern after statin treatment. We suggest that clinical studies with extended treatment periods are performed where higher dosages of statins are used. We also believe that the pleiotropic effects of statins should be investigated further in order to elucidate the connection between Alzheimers disease and statin treatment.     

Role of Na/K-ATPase in Regulation of Neurite Growth in Sensory Neurons

We studied the effects of acetylcholine and norepinephrine on the growth of neurites in organotypic culture of 10–12-day-old chick embryo sensory neurons. Acetylcholine (10^–8 M) and norepinephrine (10^–13 M) stimulated the growth on sensory neuron neurites. Experiments with combined application of acetylcholine and norepinephrine against the background of ouabain showed that the nonspecific action of the test neurotransmitters is related to modulation of Na/K-ATPase activity.__________Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 139, No. 2, pp. 157–159, February, 2005     

Studies of the effects of fragment (25–35) of beta-amyloid peptide on the behavior of rats in a radial maze

Decreases in cognitive functions, particularly long-term (episodic) and working memory, are among the earliest prognostic signs of Alzheimers disease. The toxicity of -amyloid peptide is regarded as a major cause of neurodegeneration and cognitive impairment in this disease. The present report describes studies of the effects of intracerebroventricular administration of -amyloid peptide (25–35) (A(25–35)) on the reproduction of a previously assimilated habit consisting of finding food in an eight-arm radial maze in rats. A (25–35) was given bilaterally at doses of 15 and 30 nmol/animal seven days after preliminary training. Testing was performed 60 days after peptide administration. The results showed that A(25–35) impaired working memory in rats without having any significant effect on the retention of responses. We were unable to demonstrate any relationship between memory impairment and the dose of peptide given. These data provide evidence of the ability of A(25–35) to produce greater degradation of working memory function than long-term memory function.Translated from Zhurnal Vysshei Nervnoi Deyatelnosti, Vol. 54, No. 3, pp. 382–389, May–June, 2004.     

De novo COX2 mutation in a LHON family of Caucasian origin: implication for the role of mtDNA polymorphism in human pathology

Recent studies suggest that certain mutations with phylogeographic importance as haplogroup markers may also influence the phenotypic expression of particular mitochondrial disorders. One such disorder, Lebers hereditary optic neuropathy (LHON), demonstrates a clear expression bias in mtDNAs belonging to haplogroup J, a West Eurasian maternal lineage defined by polymorphic markers that have been called secondary disease mutations. In this report, we present evidence for a de novo heteroplasmic COX2 mutation associated with a LHON clinical phenotype. This particular mutation—at nucleotide position 7,598—occurs in West Eurasian haplogroup H, the most common maternal lineage among individuals of European descent, whereas previous studies have detected this mutation only in East Eurasian haplogroup E. A review of the available mtDNA sequence data indicates that the COX2 7598 mutation occurs as a homoplasic event at the tips of these phylogenetic branches, suggesting that it could be a variant that is rapidly eliminated by selection. This finding points to the potential background influence of polymorphisms on the expression of mild deleterious mutations such as LHON mtDNA defects and further highlights the difficulties in distinguishing deleterious mtDNA changes from neutral polymorphisms and their significance in the development of mitochondriopathies.     

Visual and somatosensory processing in the macaque temporal cortex: the role of ‘expectation’

Summary The somatosensory and visual properties of cells in a polymodal region of temporal cortex were studied in 4 awake behaving macaque monkeys. When stimulated passively and out of sight, cells with tactile responses were found to have very large receptive fields covering most of the body surface and an apparent lack of selectivity for size, shape or texture of the tactile stimulus. These properties are equivalent to those described for the anaesthetized preparation (Bruce et al. 1981). Our study revealed that tactile responses were influenced by the degree to which stimuli could be expected. Tactile stimulation arising from active exploration of novel surfaces produced vigourous neuronal responses but equivalent stimulation of the skin arising when the monkey contacted expected surfaces such as itself or items with which it had become familiar produced no responses. The responses of cells to active or passive tactile stimulation were attenuated when the monkey could see the objects causing the stimulation. For cells responsive to more than one sensory modality, visual and somatosensory responses were associated in a compatible manner. Cells responsive to the onset of touch were selective for the sight of objects moving towards the monkey, whereas cells selective for the offset of touch were responsive to the sight of movements away from the monkey.     

Tissue that has lost its track: Warthin’s tumour

The origin of cystadenolymphoma (Warthins tumour) of the parotid gland is unknown. According to the most favoured hypothesis, Warthins tumour results from the proliferation of salivary gland ductal cells that were entrapped in parotid lymph nodes during embryonal life. If this is correct, and the almost total lack of recurrence and malignant transformation of this lesion lends credence to this view, Warthins tumour is correctly classified in the group of tumour-like lesions and should not be considered to be a monomorphic adenoma.     

The effects of attention and handedness on coordination dynamics in a bimanual Fitts’ law task

Two experiments were conducted to investigate the effects of attention and handedness on bimanual coordination in the context of a dynamical model of coordinated movements. Participants performed a bimanual, rhythmic Fitts law task in which the relative amount of attention directed to each task was manipulated by the relative difficulty associated with the pair of targets that each hand tapped. In both experiments, participants tended to lead with their preferred hand. The effects of attention, though, were mixed, which suggested that there was a combined effect of an attentional asymmetry and an asymmetry in the hands uncoupled frequency, both of which are captured in the dynamical model.     

Abnormal resonance behavior of the postural control loop in Parkinson’s disease

Human postural control of upright stance sporadically can show an oscillatory behavior. Based on previous work, we assessed whether an abnormal tendency for such oscillations might contribute to the motor impairments in patients with basal ganglia dysfunction such as Parkinsons disease (PD). We investigated postural control during unperturbed stance in normal control subjects and in PD patients off and under treatment, focusing on stabilogram diffusion analysis (SDA) of the foot center of pressure (COP) excursions and conventional measures of the sway amplitude and velocity. We found abnormal 1 Hz body sway oscillation in the SDA curves of PD patients that differed significantly from the body sway typically observed in control subjects during quiet stance. The 1 Hz body sway oscillation was associated with abnormally large and fast sway in the patients off treatment. Under treatment with levodopa, with deep brain stimulation (subthalamic nucleus) and even more so with combined treatment, the oscillations in the SDA curves vanished and the sway became slower. The loss of oscillation and reduction of sway velocity were highly correlated with the improvements of patients clinical motor assessment score. However, sway amplitude was not correlated with the patients motor assessment score and patients reported clinical improvement under therapy even though sway amplitude increased on average. A simple feedback model of the postural control system with abnormally large internal noise could predict experimental measures both on and off treatment. The off treatment condition was consistent with a high motor gain in the feedback loop, and the on treatment condition with a reduced motor gain.     

Disruptions in joint control during drawing arm movements in Parkinson’s disease

Impairments in control of multi-joint arm movements in Parkinsons Disease (PD) were investigated. The PD patients and age-matched elderly participants performed cyclical arm movements, tracking templates of a large circle and four differentially oriented ovals on a horizontal table. The wrist was immobilized and the movements were performed with shoulder and elbow rotations. The task was performed with and without vision at a cycling frequency of 1.5 Hz. Traces of the arm endpoint, joint-motion parameters represented by range of motion and relative phase, and joint-control characteristics represented by amplitude and timing of muscle torque were analyzed. The PD patients provided deformations of the template shapes that were not observed in movements of elderly controls. The deformations were consistent for each shape but differed across the shapes, making quantification of impairments in the endpoint movement difficult. In contrast, the characteristics of joint control and motion demonstrated systematic changes across all shapes in movements of PD patients, although some of these changes were observed only without vision. A specification of the PD influence was observed at the level of joint control and it was not distinguishable in joint and endpoint motion, because of the property of multi-joint movements during which control at each joint influences motion at the other joints. The results suggest that inability of PD patients to provide fine muscle torque regulation coordinated across the joints contributes to the altered endpoint trajectories during multi-joint movements. The study emphasizes the importance of the torque analysis when deficits in multi-joint movements are investigated, because specific impairments that can be detected in joint-control characteristics are difficult to trace in characteristics of joint and endpoint kinematics, because of interactions between joint motions.     

Programmed Cell Death of Peripheral Blood B Cells Determined by Laser Scanning Cytometry in Sjögren’s Syndrome with a Special Emphasis on BAFF

Functionally impaired B cells play an important role in the pathogenesis of Sjögrens syndrome (SS). The aim of the study was to investigate the apoptosis susceptibility of peripheral blood B cells from patients with SS and the impact of B cell activating factor (BAFF) on the apoptosis capability of these cells in correlation with IgG production. Peripheral blood B cells were isolated and stained for apoptosis markers (Bax, Bcl-2) and members of the TNF-R superfamily, CD95 and CD40. The apoptosis frequency of cells bearing these markers were assessed. Also, the apoptosis capability of cultured B-lymphocytes was investigated in medium alone, with anti-CD95 or with soluble BAFF. Quantitative ELISA was performed to detect plasma levels of sBAFF. Furthermore, the level of circulating B-cell cytokines was measured. BAFF levels were compared between patients with normal and elevated IgG levels. In SS, Bcl-2 positive B cell counts were significantly higher then in controls, also in this population the apoptosis frequency was reduced. Apoptosis within Bax+ and CD40+ B cells were significantly decreased in patients. BAFF induced a significant antiapoptotic effect in SS; also this effect was clearly evident in B cells from SS with hypergammaglobulinaemia. Plasma BAFF levels were significantly higher in SS, mostly in patients with hypergammaglobulinaemia. Plasma B-cell cytokines were raised in SS. In Sjögrens syndrome B cells, a general antiapoptotic tendency might lead to prolonged B-cell survival driven at least partly by elevated levels of BAFF and supposedly by B-cell cytokines. Also, the exaggerated BAFF stimulation might lead to excessive immunoglobulin production. The B-cell apoptosis defects, the increased BAFF levels—correlating with hypergammaglobulinaemia—together with the raised B-cell cytokine levels indicates the disturbed B-cell biology in the disease.     

Neuronal activity in the flocculus of the alert monkey during sinusoidal optokinetic stimulation

Summary 1. Activity of single units was recorded in the flocculus of alert, behaving monkeys during sinusoidal optokinetic (0.02–5.0 Hz), constant velocity optokinetic, vestibular and visual-vestibular conflict stimulation. The maximal stimulus velocity for sinusoidal optokinetic stimulation at different frequencies was 40 deg/s or less (at frequencies above 1 Hz). For an amplitude series at 0.2 Hz, stimulus velocity was varied between ±10 to ±80 deg/s. In one trained monkey activity was also investigated during smooth pursuit eye movements and suppression of the vestibulo-ocular reflex by visual fixation (VOR-supp.). Only neurons which responded to 0.2 Hz (±40 deg/s) optokinetic stimulation were included in the study. 2. The majority of neurons (44 out of 59) were type I Purkinje cells (PCs), which increased their simple spike activity during optokinetic cylinder rotation to the ipsilateral recording side. The responses during other, vestibular related, paradigms allowed all these neurons to be classified as so called gaze velocity PCs. Three type II PCs were encountered, which responded similarly, but were only weakly modulated. 3. All type I PCs were modulated at frequencies of sinusoidal optokinetic stimulation between 0.05 and 2.5 Hz. PC's showed little or no modulation at 0.03 and 0.02 Hz. About half of the PC's still responded at 5.0 Hz. 4. Relative to eye velocity, the PC activity had a phase advance of about 30 deg between 0.1 and 2 Hz. It became larger at lower, and smaller at higher, frequencies. Eye velocity related sensitivity (imp/s/deg/s) was small at low stimulus frequencies and increased monotonically, on average from 0.16 at 0.02 Hz to 2.0 at 3.3 Hz. 5. Ten (out of 12) mossy fiber related input neurons were classified as visual neurons, since their activity could be related to the amount of retinal slip in all conditions. Neurons were clearly modulated at sinusoidal optokinetic stimulation up to 5 Hz. One input neuron, investigated during sinusoidal OKN, smooth pursuit eye movements, VOR and VOR-supp., behaved qualitatively like a gaze velocity PC. The remaining input neuron encoded eye velocity at 0.2 Hz optokinetic, vestibular and visual-vestibular conflict stimulation. 6. The results show that during sinusoidal and constant velocity optokinetic stimulation gaze velocity PC's do not encode eye velocity and/or eye acceleration. 7. The vestibular nuclei-flocculus complementary hypothesis (Waespe and Henn 1981) can explain PC responses to a large extent. However, a direct comparison shows that at low frequencies (particularly around 0.05 Hz) the complementary responses of most velocity storage encoding vestibular nuclei neurons and floccular PC's appears insufficient to account fully for the oculomotor response.Supported by Deutsche Forschungsgemeinschaft SFB 220, D7R.B. was a Alexander v. Humboldt fellow.     

Natural antioxidant L-carnosine inhibits LPO intensification in structures of the auditory analyzer under conditions of chronic exposure to aminoglycoside antibiotics

Intragastric administration of L-carnosine suspension to Wistar—Kyoto rats 3 days before and after 7-day course of intraperitoneal injections of ototoxic aminoglycoside antibiotic kanamycin compensated expenditures of tissue antioxidant systems and significantly eliminated kanamycin-induced intensification of MDA production in tissues of the membrane part of the cochlea and in the auditory cortex of the temporal lobe. L-NAME (competitive NO synthase inhibitor) also inhibited LPO, increased total antioxidant activity, and decreased ototoxicity of kanamycin, which confirms the contribution of NO into LPO intensification under conditions of aminoglycoside treatment. Inhibition of pathological intensification of LPO processes and increase in total antioxidant activity under conditions of induced acute aminoglycoside ototoxicity characterizes L-carnosine as a highly effective otoprotector.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 10, pp. 408–411, October, 2004     

Expression of inflammatory secretory phospholipase A2 and cytosolic phospholipase A2 in premalignant and malignant Barrett’s oesophagus

Aims To establish the prevalence of inflammatory secretory phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) expression in a surgical series of Barretts adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis.Methods sPLA2 and cPLA2 were analysed by means of immunohistochemistry in surgical specimens of 67 and 73 cases of Barretts adenocarcinomas, respectively. Barretts mucosa was analysed in 31 cases.Results Expression of sPLA2 was detected in 48% of Barretts mucosa negative for intraepithelial neoplasia and 63% of Barretts adenocarcinoma. Semi-quantitative analysis revealed a significant increase in sPLA2 expression between Barretts mucosa negative for intraepithelial neoplasia and adenocarcinoma. cPLA2 expression was detected in 18% of Barretts adenocarcinoma. An inverse correlation was found between cPLA2 expression and depth of tumour infiltration, neoplastic vascular invasion and neoplastic perineural invasion. Survival analysis showed no significant prognostic value for sPLA2 and cPLA2.Conclusion sPLA2 is frequently expressed in Barretts oesophagus. The increasing expression of sPLA2 that we observed from Barretts mucosa to adenocarcinoma suggests that sPLA2 could be involved in Barretts carcinogenesis. In contrast, cPLA2 expression is less frequently observed in Barretts oesophagus and is inversely associated with aggressive pathological features of the tumours.     

Association study between the IL4, IL13, IRF1 and UGRP1 genes in chromosomal 5q31 region and Chinese Graves’ disease

Graves disease (GD) was believed to be a polygenic disease. Several chromosomal regions were linked to GD, and the 5q31 chromosome regions containing several interleukin genes cluster were worth observing. In this study, IL4, IL13, IRF1 and UGRP1 genes were sequenced, and 5, 3, 7 and 7 polymorphisms respectively were discovered. Then an extended association study for the attracting polymorphisms was performed with 146 sporadic Graves patients, 142 unrelated controls and the 54 multiplex Graves families. However, the genotype and allele frequency distribution of these polymorphisms had similar distribution between the Graves patients and unrelated controls, and transmission disequilibrium tests indicated that none of them showed dominant transmission from heterozygous parents to the affected offsprings. Comparison of the clinical variables of the Graves patients indicated that the onset ages of the patients carrying TT at IRF1 6477 T/G locus were younger than those having variant allele (TG, GG); the difference was of statistical significance (P=0.005, Pc=0.020). Our association study revealed that, IL4, IL13, IRF1 and UGRP1 genes in chromosomal 5q31 regions might not confer susceptibility to Chinese GD. But those individuals who were TT homozygous at IRF1 6477 T/G locus seemed to be attacked by GD much earlier than others.Huang Wei and Teng Weiping equally contributed to this work     

Diversity in receptive field properties of vertical neuronal arrays in the crown of the postcentral gyrus of the conscious monkey

Summary Single neuronal activity was recorded in the crown of the postcentral gyrus (areas 1 and 2) in 5 conscious monkeys. A total of 93 penetrations were made in the hand and finger region of 9 hemispheres and 827 neurons were isolated. The receptive field characteristics of neurons recorded along each of 88 penetrations which entered perpendicularly to the cortical surface were compared. The majority of neurons in this region were responsive to skin stimulation. In 54 penetrations, neurons related to different sensory submodalities were mixed. In 30, skin neurons predominated, and in 8, deep neurons, while in the remaining 16 penetrations neurons related to different submodalities were equally mixed. In 16 penetrations, neurons responded exclusively to stimulation of skin, hair or nails. In 9 penetrations, neurons were exclusively related to joint manipulation or other types of deep submodality. In 9 penetrations, unidentified neurons were in the majority. In each penetration, the receptive field positions varied considerably on the same finger or encompassed more than one finger. Although neurons of the same submodality, either skin or deep tended to be set in an array, the most adequate stimulus could vary among neurons of a given array. The variability in the receptive field positions or the most adequate stimuli remained constant irrespective of the angle of the electrode penetration in the cortex. The results are compatible with the idea that vertically arranged neuronal array receive inputs of multiple sources, both thalamacortical and corticocortical, so that interactions between different inputs can readilly occur.Supported by grants from the Japanese Ministry of Education