Decoding the activity of grasping neurons recorded from the ventral premotor area F5 of the macaque monkey.

Many neurons in the monkey ventral premotor area F5 discharge selectively when the monkey grasps an object with a specific grip. Of these, the motor neurons are active only during grasping execution, whereas the visuomotor neurons also respond to object presentation. Here we assessed whether the activity of 90 task-related F5 neurons recorded from two macaque monkeys during the performance of a visually-guided grasping task can be used as input to pattern recognition algorithms aiming to decode different grips. The features exploited for the decoding were the mean firing rate and the mean interspike interval calculated over different time spans of the movement period (all neurons) or of the object presentation period (visuomotor neurons). A support vector machine (SVM) algorithm was applied to the neural activity recorded while the monkey grasped two sets of objects. The original set contained three objects that were grasped with different hand shapes, plus three others that were grasped with the same grip, whereas the six objects of the special set were grasped with six distinctive hand configurations. The algorithm predicted with accuracy greater than 95% all the distinct grips used to grasp the objects. The classification rate obtained using the first 25% of the movement period was 90%, whereas it was nearly perfect using the entire period. At least 16 neurons were needed for accurate performance, with a progressive increase in accuracy as more neurons were included. Classification errors revealed by confusion matrices were found to reflect similarities of hand grips used to grasp the objects. The use of visuomotor neurons' responses to object presentation yielded grip classification accuracy similar to that obtained from actual grasping execution. We suggest that F5 grasping-related activity might be used by neural prostheses to tailor hand shape to the specific object to be grasped even before movement onset.

Secondary hyperparathyroidism and brown tumor in dialyzed patients.

Secondary hyperparathyroidism is one of the most common complications of chronic renal failure (CRF). Its pathogenesis is multifactorial and still not completely understood. Pathological mechanism of hypocalcemia, hyperphosphatemia and calcitriol deficiency are basic characteristics of CRF and main reason for morphological changes in parathyroid glands and hyperparathyroidism (HP). We present a case of a female patient born in 1975. At the age of 10, a urinary infection was diagnosed for the first time and treated. Six years later, as nausea and vomiting started, CRF based on bilateral reflux was diagnosed and the patient was included in the hemodialysis treatment. The patient was again examined in 1997, when biochemical parameters, including the level of parathyroid hormone, ultrasonography of the neck, scintigraphy of the skeleton and densitometry revealed secondary HP. Parathyreoidectomy was perfomed in 1998. During the follow up period, a tumefaction on a ramus mandibulae dex. was noticed, which was cytologically diagnosed as osteitis fibrosa, "brown tumor", a rare complication of the secondary HP. Surgery was performed and PHD was granuloma gigantocelulare. Prevention and therapy of secondary HP is a problem that demands early actions to avoid possible complications.

Morphologic and functional changes of left ventricle in dialyzed patients after treatment with recombinant human erythropoietin (r-HuEPO).

Dysfunction of the cardiovascular system is a common complication of chronic renal insufficiency. Many factors can cause left ventricular hypertrophy (LVH), and hypertension and anemia are among them. They play an important role in the pathogenesis of LVH as well as in the development of cardiac dysfunction. Echocardiography enables early detection of functional macrocirculatory changes as well as adequate measuring of cardiac structures and LV mass. Anemia of end-stage chronic renal insufficiency (ESRD) is only one among its many complications and has complex pathogenesis; one of the primary factors causing anemia is insufficient production of erythropoietin, a leading factor in the production of erythropoiesis. Anemia correction with recombinant human erythropoietin (r-HuEPO) in ESRD has a positive effect on the cardiovascular system. In this study the authors examined the hemodynamic effect of erythropoietin in anemic patients undergoing hemodialysis and observed its positive effect on the cardiovascular system. Twenty-two patients were included in the study (13 men and 9 women) mean age x=39.5 years. All patients were dialyzed three times a week for 4 hours and were all (Abstract continued) treated, according to protocol, with r-HuEPO for 8 months. Left ventricular mass was measured by the Penn Convention formula. The authors noticed the effectiveness of this therapy through an increase of hemoglobin of 35% and of hematocrit of 34% and a direct effect on the cardiovascular system. Echocardiographic findings showed decrease of LV mass from 391 to 274 mg (30%). The correction of renal anemia with erythropoietin leads to structural microcirculatory changes and partial morphologic regression of preexistent LVH, which again leads to regression of cardiac dysfunctions and improved hemodynamic effect, physical capacity, and cardiopulmonary status, and ultimately better quality of life for dialyzed patients.

Visual responses in the dorsal premotor area F2 of the macaque monkey.

This study aimed to determine the presence of neurons responding to visual stimuli in area F2 of the dorsal premotor cortex of the macaque monkey. In order to delimit the sector in which visually responsive neurons are located, the somatotopic organization of area F2 was studied with intracortical microstimulation and single neuron recording. The results showed that: (1) in area F2 there is a significant percentage of visually responsive neurons (15.9% of all recorded neurons); (2) area F2 is excitable with a low-threshold current (average 28.1 microA) and has a somatotopic representation of the whole body, except the face; and (3) most visually driven neurons (n=130 out of 169) are concentrated within the rostrolateral sector of the forelimb representation of area F2, thus providing for the first time functional support for the neuroanatomical evidence that the visual input to area F2 is mostly restricted to this sector.

A case of McLeod syndrome with chronic renal failure.

A 50-year-old man with the rare McLeod syndrome, associated with glomerular lesion to the end stage of chronic renal failure and death, is reported. McLeod syndrome is an X-linked recessive disorder on the basis of abnormal expression of the Kell blood group antigens and absence of erythrocyte surface Kx antigen. Most often the clinical and pathological findings are retinitis pigmentosa to blindness, progressive chronic neuropathy, cortical atrophy, dilated cardiomyopathy, and glomerular lesion with chronic renal failure. Among the laboratory parameters the most important are very low level of cholesterol and triglycerides, then various numbers of acanthocytes in peripheral blood smears and sometimes in urine (as in our case).

Object representation in the ventral premotor cortex (area F5) of the monkey.

Visual and motor properties of single neurons of monkey ventral premotor cortex (area F5) were studied in a behavioral paradigm consisting of four conditions: object grasping in light, object grasping in dark, object fixation, and fixation of a spot of light. The employed objects were six different three-dimensional (3-D) geometric solids. Two main types of neurons were distinguished: motor neurons (n = 25) and visuomotor neurons (n = 24). Motor neurons discharged in association with grasping movements. Most of them (n = 17) discharged selectively during a particular type of grip. Different objects, if grasped in similar way, determined similar neuronal motor responses. Visuomotor neurons also discharged during active movements, but, in addition, they fired also in response to the presentation of 3-D objects. The majority of visuomotor neurons (n = 16) showed selectivity for one or few objects. The response was present both in object grasping in light and in object fixation conditions. Visuomotor neurons that selectively discharged to the presentation of a given object discharged also selectively during grasping of that object. In conclusion, object shape is coded in F5 even when a response to that object is not required. The possible visual or motor nature of this object coding is discussed.

Comparative study of mitral annular calcification (MAC) with cardiac arrhythmias in dialysis patients.

Cardiac arrhythmias and myocardial malfunction are very frequent in uremic patients. The pathogenesis and etiology of arrhythmias are very complex and still unknown. The sedimentation of calcium salt in myocardial structures is one of the reasons for emergence of cardiac arrhythmias (AV conduction defects, ectopic arrhythmias). The appearance of mitral annular calcification (MAC), as the expression of the speed up process of atherosclerosis, was noted in younger uremic patients especially during hemodialysis. The aim of our research was to compare the incidence of MAC and cardiac arrhythmias in patients on hemodialysis. Our study included 40 patients, 24 male and 16 female, in the age between 20 and 60. Patients were mostly from Zagreb and the Counties of Zagreb (35%), Karlovac (10%), Slavonski Brod (7.5%), Varazdin (5%) and Pozega (5%). All 40 patients received 24 hours of Holter monitoring and 2-D echocardiography of M-mode. The patients were divided in two groups: I MAC+ (N = 23) and II MAC- (N = 17). Frequency of cardiac arrhythmias in group I was: atrial fibrillation N = 0; conduction defects N = 2 (1%); ventricularectopy Lown grade 3-5 N = 15 (65%); supraventricular ectopy N = 8 (34%), while the frequency of cardiac arrhythmias in group II was: atrial fibrillation N = 0; conduction defects N = 0; ventricular ectopy Lown grade 3-5 N = 6 (35%), supraventricular ectopy N = 6 (35%). During statistical processing the significant connection of MAC+ and frequency of cardiac arrhythmias was noticed. For both groups we have not noticed statistical significance in cardiac arrhythmia compared to electrolytes, risk factors PTH, and age. The time of hemodialysis treatment is one of possible factors for incidence of cardiac arrhythmias influenced by MAC. We noticed statistically significant (p < 0.05) difference of rhythm disorders between group I and group II especially for the ventricular ectopic activity, the frequency of which was higher in group I than in group II. MAC has probably significant role in dialysis patients for the development of cardiac arrhythmias within the framework of series of complicated multifactorial patogenetic mechanisms.

Spatial cortical patterns of metabolic activity in monkeys performing a visually guided reaching task with one forelimb.

The 2-[14C]deoxyglucose method was used to map the metabolic activity in the neocortex of monkeys (Macaca nemestrina) performing a visually guided reaching task with one forelimb. Monkeys received liquid reward for correct, single directional reaching movements, which were required at a rate of about 10 per minute. We estimated the weighted average of local glucose consumption within several neocortical areas, and we reconstructed quantitative, high-resolution, two-dimensional maps of the detailed spatiointensive patterns of activity. Our findings demonstrate the involvement of the striate and prestriate cortices, the inferior intraparietal and superior temporal visual association areas, the frontal eye field and the caudal periprincipal cortex, the primary somatosensory and the related superior intraparietal area, the primary and association auditory cortices, the superior temporal multimodal region, and the premotor, primary, supplementary, and cingulate motor areas. The visual cortex in the superior temporal and the intraparietal sulci, which is concerned with "where", was activated during visually guided reaching. In contrast, the inferior temporal visual association cortex, which is concerned with "what", was not involved in our study. We suggest that the activated direction-selective layer four of V1 and the thick stripes of V2 convey visuomotor information to the activated cortex in the posterior bank and the floor of the superior temporal sulcus, which may encode the constantly updated position of the moving forelimb. In parallel, the activated cortex in the ventral part and the lateral bank of the intraparietal sulcus may encode visuospatial information related to the localization of the visual target in the extrapersonal space. Furthermore, the dorsal part of the medial bank of the intraparietal sulcus may be involved in proprioceptive guidance of movement, based on the parallel metabolic effects shown only contralateral to the moving forelimb within this region and the forelimb representations in the primary somatosensory and motor cortices. Finally, the bilaterally activated network including the inferior postarcuate skeletomotor and prearcuate oculomotor cortical fields and the caudal periprincipal region 46 may participate in sensory and oculomotor to motor transformations, in parallel with the medial and lateral intraparietal cortices with which this network is reciprocally interconnected.

Effect of therapeutic interventions on CK and CK MB serum activity kinetics during acute myocardial infarct.

Determination of serum creatine kinase (CK) activity, especially the CK MB, isoenzyme is becoming the main diagnostic criterion for acute myocardial infarct (AMI). The aim of this study was to assess the kinetics of the release CK and CK MB in AMI patients on various therapeutic regimens. The study included 75 AMI patients (within 6 hours from the pain onset). They were divided into three groups according to therapy: 1.NTG i.v. (glyceryl trinitrate, N=29), 2.SK + NTG i.v. (streptokinases + glyceryl trinitrate, N = 29); and 3. SK i.v. (N = 17). Samples for CK and CK MB determination were taken every 4 hours in the course of 72 hours, until serum enzyme values returned to normal. The time interval between the introduction of therapy and CK and CK MB peak values expressed in rankes was the shortest in group 3 and longest in group 1. The difference in maximal CK release in to peripheral blood (chi 2 = 9.5270, p = 0.0180) was statistically significant, while difference in CK MB was not (chi 2 = 2.2733, p = 0.2875--NS) (Kruskal Wallis one way test). Comparing CK release time the CK MB within each group by means of rankes, statistical significance in favour of CK MB (1. NTG i.v. p = 0.0000, 2. SK + NTG p = 0.0001, 3. SK p = 0.0180) was obtained. The rate of CK and CK MB elimination from the circulation, expressed as fractional level of losing kd, did not statistically differ in the three groups. Authors' results showed the therapeutic procedures used in the treatment of AMI patients to differently influence the CK and CK MB kinetics. Thrombolytic therapy changed the CK and CK MB kinetics, due to reperfusion and explained by the washout phenomenon from the infarcted zone of the myocardium.

Acute renal failure as a complication of acute pancreatitis.

To assess the prevalence of acute renal failure (ARF) in patients with acute pancreatitis, as well as the factors predictive of a lethal outcome, we retrospectively studied the data of all patients admitted to our hospital over a 5-year period. Between 1989 and 1993, 554 patients presented with acute pancreatitis, of which 24 (4.4%) subsequently developed ARF. Death occurred in 14/24 (58%) of patients with ARF, and was associated with an increased incidence of multiorgan failure. There was no statistically significant difference in the age, admission blood pressure, or admission pulse rate of the patients who survived and those who died. In contrast, death was associated with a higher Ranson score, and the increased prevalence of multiorgan failure. The length of hospitalization of the nonsurviving group was significantly shorter. Acute renal failure is not a common finding in patients with acute pancreatitis. However, when it occurs, it is associated with a poor prognosis, and is predicted by a higher Ranson score and the presence of multiorgan failure.

Metabolic activity pattern in the motor and somatosensory cortex of monkeys performing a visually guided reaching task with one forelimb.

The [14C]deoxyglucose method was used to map the metabolic activity in the primary somatosensory and motor cortex in monkeys (Macaca nemestrina) performing a unimanual task. The task required visually guided reaching and target holding at a rate of about 10 movements per min. The entire dorsoventral extent of the cortical region lying between the posterior crown of the arcuate and the anterior crown of the intraparietal sulci was reconstructed on the sagittal plane, from horizontal sections aligned on the fundus of the central sulcus. The metabolic mapping of the control monkey demonstrated homogeneous activity all around the central sulcus, bilaterally. The mapped activity in the performing monkeys displayed two different patterns. The first pattern, contralateral to the moving forelimb, was characterized by several discrete regions of increased metabolic activity, which were symmetrically distributed in a mirror image fashion around the fundus of the central sulcus. These activated regions correspond to the lower body, forelimb, and mouth areas of representation of body parts in previously reported maps in primary motor and somatosensory cortical areas. The second activity pattern ipsilateral to the moving forelimb, displayed activated somatosensory and motor regions corresponding only to the lower body, and mouth representations. Our study provides a continuous, high resolution map of activity pattern in the entire primary motor and somatosensory cortices, which demonstrates that the reaching forelimb is controlled by a discrete subregion in the contralateral somatosensorimotor cortex, whereas other subregions of body representation are actively involved, bilaterally, during the performance of a relatively simple motor behaviour.

Frequency of mitral annular calcification in patients on hemodialysis estimated by 2-dimensional echocardiography.

Mitral annular calcification (MAC) is a degenerative process associated with left ventricular hypertrophy (HLV) and progressive atherosclerosis, characteristic of the older age groups. Numerous investigations point to significantly earlier onset of atherosclerosis process in patients in final stage of chronic renal insufficiency. The aim of investigation was to determinate the MAC frequency in patients on hemodialysis and to try to find the correlation between MAC intensity and the duration of hemodialysis, age, sex, Ca/P, metabolism, level of parathormone and atherogenic factors. A group of 40 patients on hemodialysis (aged 20 to 67, 26 men and 24 women) were divided int two groups; group 1 without MAC, N = 17 (42.5%), X = 3.5, SD = 3.1; and group 2 with MAC, N = 23 (57.5%), X = 6.2, SD = 2.4. M-mode and 2-D echocardiography were performed in all patients. Group 2 was divided into three subgroups according to MAC quantitation: mild N = 16 (70%), severe, N = 4 (17%), moderate, N = 3 (13%). Study results showed positive correlation between MAC and serum values of Ca and P (p < 0.05). Increased values of HDL cholesterol, statistically significant at the level p < 0.05 were observed. Study results showed the correlation between MAC and time factor, i.e. duration of dialysis treatment to be statistically significant (p < 0.05). Cardiac calcified syndrome could be a sequela of MAC causing conduction disturbances, valvular stenosis or insufficiency, and arterial emboli or endocarditis.

Functional anatomy of the thalamic reticular nucleus as revealed with the [14C]deoxyglucose method following electrical stimulation and electrolytic lesion.

The [14C]-deoxyglucose quantitative autoradiographic method was used to map the metabolic changes induced by electrical stimulation and electrolytic lesion of the rostral pole of the thalamic reticular nucleus in the rat brain. Unilateral electrical stimulation of the thalamic reticular nucleus induced the following changes in glucose utilization: (i) local enhancement of metabolic activity within the stimulated thalamic reticular nucleus, (ii) increase in glucose consumption in the ipsilateral thalamic mediodorsal, centrolateral, ventromedial and ventrolateral nuclei, as well as in the nucleus accumbens, (iii) bilateral depression of metabolism in the locus coeruleus, periaqueductal gray, ventral tegmental area, and medial habenula, as well as contralateral metabolic depression in the substantia nigra reticulata, compacta and in the ventral pallidum. Unilateral electrolytic lesion of thalamic reticular nucleus elicited metabolic depression in the ipsilateral thalamic mediodorsal, centrolateral, ventrolateral and ventromedial nuclei, and metabolic activation in the dorsal tegmental nucleus bilaterally. The existence of a descending thalamic reticular nucleus input to the periaqueductal gray is supported by the depressed activity measured in brain stem structures after thalamic reticular nucleus stimulation. The similar effects observed in the periaqueductal gray and substantia nigra contralateral to the stimulated thalamic reticular nucleus indicate a possible flow of information from one thalamic reticular nucleus to the contralateral basal ganglia via the periaqueductal gray. The opposite effects induced in the dorsal thalamic nuclei by thalamic reticular nucleus stimulation and lesion support the gating role of the thalamic reticular nucleus in the information flow between thalamus and cortex.

Functional anatomy of the thalamic centrolateral nucleus as revealed with the [14C]deoxyglucose method following electrical stimulation and electrolytic lesion.

The effects of electrical stimulation and electrolytic lesion of the thalamic intralaminar centrolateral nucleus were studied in the rat brain by means of the quantitative autoradiographic [14C]deoxyglucose method. Unilateral electrical stimulation of the centrolateral nucleus induced: (i) local increase in metabolic activity within the stimulated centrolateral nucleus and the ipsilateral thalamic mediodorsal nucleus, (ii) metabolic depression in all layers of the ipsilateral frontal cortex, (iii) bilateral increase in glucose consumption within the periaqueductal gray, pedunculopontine nucleus, and pontine reticular formation, and (iv) contralateral metabolic activation in the deep cerebellar nuclei. The unilateral electrolytic lesion of the thalamic centrolateral nucleus elicited metabolic depressions in several distal brain areas. The metabolic depression elicited in the mediodorsal, ventrolateral, and lateral thalamic nuclei, as well as in the caudate nucleus, the cingulate, and the superficial layers of forelimb cortex were ipsilateral to the lesioned side. The metabolic depression measured in the medulla and pons (medullary and pontine reticular formation, periaqueductal gray, locus coeruleus, dorsal tegmental, cuneiformis, raphe and pedunculopontine tegmental nuclei), the cerebellum (molecular and granular layers of the cerebellar cortex, interpositus and dentate nuclei), the mesencephalon (substantia nigra reticulata, ventral tegmental area and deep layers of the superior colliculus), the diencephalon (medial habenula, parafascicular, ventrobasal complex, centromedial and reticular thalamic nuclei), the rhinencephalon (dentate gyrus and septum), the basal ganglia (ventral pallidum, globus pallidus, entopeduncular and accumbens nuclei) and the cerebral cortex (superficial and deep layers of the frontal and parietal cortex, deep layers of the forelimb cortex) were bilateral. These functional effects are discussed in relation to known anatomical pathways. The bilateral effects induced by the centrolateral nucleus lesion reflect an important role of the centrolateral nucleus in the processing of reticular activating input and in the interhemispheric transfer of information. The cortical metabolic depression induced by centrolateral nucleus stimulation indicates the participation of this nucleus in attentional functions.

The effect of intravenous nitroglycerin therapy on infarct size in patients with acute myocardial infarction.

The authors investigated the influence of glyceryl-trinitrate (NTG) given intravenously to the reduction of infarction size in 95 patients (71 men and 24 women) aged 36 to 75, with acute myocardial infarction (AIM) admitted to the Intensive Care Unit within six hours of the onset of pain. Infarction mass was calculated by mathematical model from the serial changes of CK and CK MB serum activities during 72 hours and expressed in CK and CK MB gEq. CK and CK MB were determined every four hours. The patients were divided into four groups according to the therapy they were receiving: I--NTG i.v. (n = 29); II SK + NTG i.v. (n = 29); III SK i.v. (n = 17) and IV ISDN per os (n = 20). Each group was divided into subgroups regarding the time interval from the onset of pain to the beginning of the therapy (within three hours and after three hours). Application of NTG i.v. in the early phase of AIM, 0-3 hours from the onset of pain, led to the significant reduction of infarction mass CK gEq and CK MB gEq (0-3 hours; middle rank = 11.35; 3-6 hours: middle rank = 17.7) (P < 0.05) and 0-3 hours: middle rank = 10.31; 3-6 hours: middle rank = 18.81 (P < 0.01). It was established that the "timing" factor was very important in the preservation of myocardial mass in AIM. It affirms the efficacy of NTG i.v., i.e., its direct effects on the coronary arteries and systemic effects that cause salvation of the myocardium. The influence of NTG iv to myocardial infarction size CK gEq did not depend on ECG localization. But it influenced the ECG localization when the infarction size was calculated from CK MB isoenzyme and expressed in CK MB gEq. Infarction mass CK MB gEq was statistically significantly smaller in the inferior than in the anterior localization (P < 0.05).

Aldosterone and blood pressure in obese subjects during short-term starvation.

Changes in plasma renin activity (PRA) and aldosterone concentration during 10 days of starvation were studied, together with the relationship among PRA, aldosterone, plasma volume, sodium balance and mean blood pressure (MBP). Study subjects were 16 obese individuals (13 females and 3 males; age ranged 18-50 years) with a body mass index greater than 30 kg/m2. Total fasting induced a significant decrease in body weight, MBP, plasma volume and urinary sodium concentration, and a rise in PRA and aldosterone concentration. Before starvation, there was a significant correlation between aldosterone concentration and MBP. This data support the hypothesis that aldosterone is one of the factors which elevate blood pressure in obese subjects. Much of the initial fall in blood pressure during starvation seemed to be due to an imbalance between the cessation of sodium intake and excessive natriuresis.

Crosstalk between the two sides of the thalamus through the reticular nucleus: a retrograde and anterograde tracing study in the rat.

In order to investigate the possible routes linking the thalamus in the two sides of the brain, the connections of the reticular nucleus (RT), the major component of the ventral thalamus, with contralateral dorsal thalamic nuclei were systematically investigated in the adult rat. This study was performed with several tract-tracing techniques: single and double retrograde labeling with fluorescent tracers, and anterograde tracing with biocytin. Retrograde tracing was also combined with immunocytochemistry to provide additional criteria for the identification of labeled RT neurons. The data obtained with the retrograde transport of one fluorescent tracer showed that RT neurons project to contralateral dorsal thalamic domains. In particular, retrograde labeling findings indicated that the anterior intralaminar nuclei, as well as the ventromedial (VM) nucleus, are preferential targets of the contralateral RT projections. Commissural neurons were concentrated in two portions of RT: its rostral part, including the rostral pole, which projects to the contralateral central lateral (CL) and paracentral (Pc) nuclei, and the ventromedial sector of the middle third of RT, which projects to the contralateral VM and posterior part of CL and Pc. The double retrograde labeling study of the bilateral RT-intralaminar connection indicated that at least part of the commissural RT cells bifurcate bilaterally to symmetrical portions of the anterior intralaminar nuclei. The targets of the RT commissural system inferred from the retrograde labeling data were largely confirmed by anterograde tracing. Moreover, it was shown that RT fibers cross the midline in the intrathalamic commissure. The present data demonstrate that bilateral RT connections with the dorsal thalamus provide a channel for interthalamic crosstalk. Through these bilateral connections with thalamic VM and intralaminar neurons, RT could influence the activity of wide territories of the cerebral cortex and basal ganglia of both hemispheres.

Connections of the thalamic reticular nucleus with the contralateral thalamus in the rat.

The occurrence of thalamic projections to the contralateral side of the thalamus, and the origin of these projections from the thalamic reticular nucleus, were demonstrated with fluorescent retrograde tracing. After a relatively large tracer injection in the anterior third of the thalamus (involving the reticular, anterior, intralaminar and ventrolateral nuclei), labeled cells were detected in the rostral portion of the contralateral reticular nucleus. The location within the reticular nucleus of the neurons retrogradely labeled in the contralateral thalamus was confirmed by means of the combination of tracing with immunocytochemistry, using antibodies against the calcium binding protein parvalbumin.

Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the inhibitory GABAA receptor agonist muscimol.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D[1-14C]glucose technique in the rat brain in order to determine the metabolic effects of unilateral intranigral application of the GABAA agonist muscimol upon the substantia nigra and its targets. Intranigral injection of 1.5 microliters 0.3 M muscimol (52 micrograms total dose) induced local metabolic activation in the injected substantia nigra reticulata (by 87% as compared to the control group), and distal metabolic depressions in the nucleus accumbens, striatum, globus pallidus and subthalamic nucleus only ipsilaterally to the injected nigra. The remaining basal ganglia components, including the substantia nigra compacta and the entopeduncular nucleus were bilaterally unaffected. Among the principal efferent projections of the substantia nigra reticulata, the ventromedial and centrolateral thalamic nuclei as well as the deep layers of the superior colliculi were metabolically depressed bilaterally, whereas the ventrolateral, parafascicular and mediodorsal thalamic nuclei as well as the pedunculopontine nucleus displayed metabolic depressions ipsilateral to the muscimol-injection nigra. The ventromedial and centrolateral thalamic nuclei were depressed by 41 and 42%, respectively, in the ipsilateral side, and by 30 and 26% in the contralateral side, when compared to the respective values of the control group of rats. Furthermore, unilateral intranigral injection of 0.3 M muscimol induced metabolic depressions in reticular, intralaminar and prefrontal thalamocortical areas mostly ipsilateral to the injected nigra, as well as in limbic areas bilaterally. It is suggested that the present findings are due to a postsynaptic effect of muscimol on the nigral GABAergic cells and to a consequent metabolic depression of the basal ganglia and associated thalamocortical areas, in contrast to an earlier suggested presynaptic nigral effect of lower doses of intranigrally injected muscimol which induced metabolic activations within the same network. This suggestion is further supported by the fact that intranigrally injected substrate P19 induced similar effects to those elicited by the lower doses of intranigral muscimol and opposite to those induced at present by the higher muscimol dose. Moreover, it is further substantiated that the nigrothalamic GABAergic system is responsible for considerable transfer of information from one substantia nigra reticulata to the ipsilateral basal ganglia and associated thalamocortical components as well as to bilateral motor, intralaminar and limbic areas.