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Biomedical subjects

C D Balaban

Publications and source records attributed to C D Balaban.

At least 91 records · Page 5Linked to original sources

Barrel rotation evoked by intracerebroventricular vasopressin injections in conscious rats. II. Visual/vestibular interactions and efficacy of antiseizure drugs.

Intracerebroventricular (i.c.v.) arginine-vasopressin (AVP) injections evoke 'barrel rotation' (BR) in rats. This motor system abnormality was studied in a protocol where conscious rats were injected on day 1 with 1 microgram i.c.v. AVP and reexposed to 0.5 micrograms on day 3. Three paradigms modifying visual/vestibular systems were employed: labyrinthectomy, 3-acetylpyridine (3-AP) destruction of the inferior olive and atropine pretreatment. Ambient illumination (light vs dark) was also modified. Initial (day 1) incidence of BR, increased incidence (i.e. sensitization) on day 3, and day 3 BR latency were differentially affected by the various paradigms and suggest a complex role of visual/vestibular input in modifying i.c.v. AVP-induced BR. For example, 3-AP rats tested in light and atropinized rats had a reduced responsiveness to the peptide on day 1. 3-AP-treated rats tested in dark conditions showed a normal incidence of BR on day 1, but the expected sensitization to AVP on day 3 did not occur. Combined labyrinthectomy and darkness did not modify BR incidence on either day, but altered the distribution of latency data. Four diverse antiepileptic drugs were tested for efficacy against i.c.v. AVP-induced BR in sensitized rats: phenytoin, diazepam, valproic acid and phenobarbital; all drugs reduced the proportion of rats with BR and prolonged the latency. We conclude that brain AVP may be involved in abnormal motor conditions that are modified by visual/vestibular neuronal circuits. The unusual motor output (barrel rotation) can be inhibited by diverse antiepileptic drugs.

Animals↗

Protein-O-carboxylmethyltransferase in the rat brain: high regional levels in the substantia nigra, locus coeruleus and paraventricular nucleus.

Immunocytochemical techniques were used to localize protein-O-carboxylmethyltransferase in the rat brain. Particularly high levels of immunoreactive protein-O-carboxylmethyltransferase were found in the paraventricular and supraoptic nucleus, the substantia nigra and the locus coeruleus. The enhanced expression of the methyltransferase in these brain regions suggests that protein carboxylmethylation is of particular importance in these areas. These findings are consistent with previous biochemical studies which suggest that protein methylation plays a role in presynaptic monoaminergic neurons and in the release and/or processing of neurohypophyseal peptides.

Animals↗

The human pre-saccadic spike potential: influences of a visual target, saccade direction, electrode laterality and instructions to perform saccades.

Three components of pre-saccadic evoked potentials have been identified in humans: a slow negative shift (SNS), a positive antecedent potential (AP) and a spike potential (SP). This study examined the influences of: instructions to the subject to make saccades; the presence of a visual target; and the direction of the saccades on the amplitude of the averaged SP, which was recorded from P3 and P4 (International 10/20 System) in 20 normal, right-handed subjects. Recordings were made for spontaneous saccades prior to receiving instructions in six subjects. Twenty subjects performed self-paced saccades in the presence of a 10 degrees visual target (two red LEDs) and while blindfolded in a dark room. The SP was either absent or grossly altered (broadened) for spontaneous saccades in an illuminated room; it was robust for self-paced saccades in light or darkness. Three-way analysis of variance revealed a highly significant cortical laterality (P3 vs P4) X saccade direction interaction (P less than 0.001), reflecting that for a given saccade direction, the SP was larger over the contralateral recording site for the self-paced light (SPL) paradigm (Newman-Keuls test). In the self-paced dark (SPD) paradigm, though, this was only true for saccades to the right. By contrast, scatter plots of the directional indices (D.I. = [(SP for contralateral) - (SP for ipsilateral)]/[(SP for contralateral) + (SP for ipsilateral saccades)] for left (P3) and right (P4) recording sites from individual subjects revealed a significant negative correlation for both SPL (r = 0.78) and SPD (r = 0.74) paradigms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: a critical review of central 3-acetylpyridine neurotoxicity.

Previous studies indicate that 3-acetylpyridine (3-AP) intoxication produces discrete lesions of the inferior olive (IO) and other central structures in rats and mice. As a result, it has been widely employed in investigations of the influences of climbing fibers on cerebellar function. This study examines the central toxicity of a protocol reported to produce lesions restricted to the inferior olive in rats. Adult male Long-Evans (n = 12) and Sprague-Dawley (n = 18) were given serial injections of 3-AP (75-80 mg/kg), harmaline (15 mg/kg) or saline, and niacinamide (300 mg/kg). Silver degeneration staining (cupric-silver method) after 6-48 h survival revealed consistent patterns of degenerating neurons in IO, nucleus ambiguus, hypoglossal nucleus, dorsal motor nucleus X, nucleus intercalatus, nucleus dorsalis raphe, medial terminal nucleus, interpeduncular nucleus, substantia nigra, ventral tegmental area, entopeduncular nucleus, hippocampus (dentate gyrus and CA 3-4), horizontal limb of the nucleus of the diagonal band, and lateral entorhinal cortex, which were not produced by control experiments with 3 saline injections or with two saline injections followed by niacinamide. These data apparently resolve conflicts in the literature regarding central 3-AP toxicity and indicate that the 3-AP-harmaline-niacinamide protocol produces degeneration that is similar to 3-AP alone. However, they also document the discrete, reproducible susceptibility of certain neuronal populations to 3-AP intoxication and suggest that the motor symptoms of intoxication are not solely due to IO destruction. Finally, they form a basis for biochemical investigations of 3-AP toxicity in susceptible central structures.

Animals↗

Localization of methadone in the brain of young rats by computer-assisted autoradiography.

The distribution of systemically administered [14C]methadone in the brain of 21-day-old rats was examined by computer-assisted autoradiography. Methadone binding differed 2.5-fold across the more than 90 neural structures examined, with the dentate nucleus having the highest levels and lamina I of the anterior parietal cortex the lowest. Since a full normal probability plot demonstrated that the binding was distributed normally across brain structures (r = 0.99), binding classes were defined in terms of 0.5 standard deviation units from the mean. In addition to marked binding differences between neuronal structures, there were prominent laminar differences in the cerebral cortex, hippocampus, superior colliculus and cerebellar cortex. These highly specific patterns of methadone localization were specifically related to the opioid receptor because naloxone blocked the antinociceptive effects of methadone on the hot-plate test and abolished the distribution of methadone binding in the central nervous system. The relatively high levels of methadone binding in layers III and V of neocortex, sensory relay nuclei, inferior olive, pontine nuclei, cerebellar nuclei and cerebellar molecular layer suggest that the constellation of physiological and neurobehavioral sequelae of perinatal opioid exposure result from specific binding at multiple sites involved in sensory, motor and integrative information processing.

Analgesics↗

A specific harmaline-evoked increase in cerebellar 5'-nucleotidase activity.

This study examines harmaline-induced changes in 5'-nucleotidase (5'-ND) activity in cerebellar fractions from rats with an intact inferior olive (IO) or prior destruction of the IO by 3-acetylpyridine (3-AP) intoxication. Harmaline markedly increased 5'-ND activity in the crude homogenate (P less than 0.05) and P2 fraction (P less than 0.001) of cerebella from rats with an intact IO. This increase was absent in the P1, P3 and S3 fractions and it was abolished by 3-AP olivectomy. It was also absent in basal ganglia P2 fractions. Since harmaline produces rhythmic complex spike discharges of Purkinje cells by activating IO neurons [4, 18], these data suggest that climbing fiber activation per se increases 5'-ND activity in the P2 fraction. This raises the possibility that a climbing fiber-induced local increase in 5'-ND activity at parallel fiber-Purkinje cell synapses results in a local increase in adenosine concentration. This may account for climbing fiber-evoked suppression of simple spike activity [12, 13, 28].

5'-Nucleotidase↗

Functional representation of eye movements in the flocculus of monkeys (Macaca fuscata).

The flocculus of the monkey was mapped with microstimulation methods in chronic preparations. Three types of low threshold, disconjugate eye movements were elicited: (1) a lateral deviation of the ipsilateral eye, (2) a downward deviation of the ipsilateral eye and (3) counterclockwise rotation of the ipsilateral eye. Horizontal eye movements were obtained from folia 2, 3, 4 and 6-10 of the flocculus, and the region eliciting horizontal eye movements was traced in the sagittal plane over a distance of 4 mm in one animal. However, sites flanking these horizontal movement sites produced either vertical movements, rotatory movements or failed to produce a movement of either eye. These findings suggest a zonal organization of flocculus functions in monkeys that is consistent with the differential projections of flocculo-vestibular connections revealed by retrograde tracing studies [2].

Animals↗

Central effects of aldosterone infused into the rat subcommissural organ region.

D-Aldosterone (5 ng/microliter/h) was infused for 6 days into the region of the subcommissural organ (SCO) of conscious, adult male Sprague-Dawley rats. Aldosterone increased urinary sodium loss and the sodium/potassium ratio. Although probably central in origin, these effects still occurred when cannulae were displaced up to 1 mm from the targeted SCO placement. Aldosterone decreased adrenal medullary cross-sectional area without affecting cell density. This effect was highly dependent on proper cannula placement and was not observed when the cannula tip was not in contact with the cerebrospinal fluid of the pineal recess over the rostral two-thirds of the SCO. We conclude that aldosterone increases sodium excretion by an action in the SCO and/or adjacent structures. We also postulate a negative trophic relationship between mineralocorticoids and the adrenal medulla mediated by the SCO.

Adrenal Glands↗

Olivo-vestibular and cerebello-vestibular connections in albino rabbits.

This study analyzes the organization of olivo-vestibular and cerebello-vestibular projections in rabbits. Iontophoretic injections of horseradish peroxidase, placed under physiological guidance into the superior, medial and lateral vestibular nuclei, produced retrogradely labeled neurons in the dorsal cap, ventrolateral outgrowth and lateral flexure of the principal olivary nucleus, the caudal half of the medial accessory olive and the caudal three-fourths of the dorsal accessory olive. This inferior olivary labeling was strictly contralateral. The same injections labeled groups of Purkinje cells in the ipsilateral cerebellar cortex, oriented perpendicular to the long axes of the folia of lobules I-V, VId-e and VIII-X of the vermis and the flocculus. The patterns of olivo-vestibular and cerebello-vestibular connections were consistent with the general hypothesis that inferior olivary axon collaterals project to both Purkinje cells and subcortical neurons inhibited by those Purkinje cells. In addition, the analysis of flocculo-nodular and dorsal cap-ventrolateral outgrowth projections to the medial and superior vestibular nuclei suggests that these connections are discrete at the level of a pool of olivary neurons which projects to functional pools of neurons in both cerebellar cortex, and in the vestibular nuclei. Thus, it is likely that inferior olivary projections define functional networks spanning cerebellar cortex and the vestibular nuclei.

Animals↗

Inferior olivary lesions after local injections of 3-acetylpyridine in rabbits.

This report presents evidence that local injections of 3-acetylpyridine (3-AP) produce circumscribed lesions of the inferior olive (IO) in rabbits. These restricted lesions, assessed in both cresyl violet-stained sections after a 14-day survival and cupric-silver-stained sections after a 16-24 h survival period, are similar in appearance to lesions produced by systemic 3-AP administration in rats. Two types of degeneration are observed: destruction of cells at the injection site and more diffuse cell death in the ipsilateral and contralateral inferior olive. The latter type of degeneration appears to result from IO fiber-of-passage uptake of 3-AP. There was no evidence of lesions in surrounding structures or in sources of axons passing through periolivary regions. Thus, this protocol is a promising tool for studies of climbing fiber connectivity and physiology in rabbits.

Animals↗

A projection from nucleus reticularis tegmenti pontis of Bechterew to the medial vestibular nucleus in rabbits.

This study documents a bilateral projection from nucleus reticularis tegmenti pontis (NRTP) to the rostral aspect of the medial vestibular nucleus (MVN) in rabbits. Horseradish peroxidase injections in rostral MVN produced retrogradely labeled neurons in the caudal half of NRTP; caudal MVN injections produced negative results. This supports the hypothesis that NRTP relays visual input to the vestibular nuclei via an extracerebellar pathway (Precht and Strata 1980), and indicates the importance of examining the contributions of both direct and cerebellar-mediated visual pathways to oculomotor physiology.

Afferent Pathways↗

Distribution of beta-D-glucuronidase in the central nervous system of albino rats.

The distribution of beta-D-glucuronidase (GLR) in the central nervous system of albino rats was surveyed with a simultaneous-coupling histochemical technique. Specific neuronal populations displayed intense GLR activity. These groups include olfactory bulb mitral cells, neurones in the deep layer of the olfactory tubercle, cells in both the horizontal and vertical limbs of the nucleus of the diagonal band, paraventricular, supraoptic and suprachiasmatic nuclear neurons, cochlear and vestibular nuclear neurons, and facial, trigeminal and spinal motoneurons. Two types of intracellular GLR staining were observed. Granular staining was prominent in mitral cells; cytoplasmic staining and a perinuclear 'ring' were prominently stained in motoneurons. These patterns may correspond to lysosomal and endoplasmic reticular distribution of GLR in different cell types.

Animals↗

Demonstration of zonal projections from the cerebellar flocculus to vestibular nuclei in monkeys (Macaca fuscata).

Purkinje cells in the flocculus of macaque monkeys were labeled by retrograde axonal transport of horseradish peroxidase from the vestibular nuclei. These neurons are organized in three adjacent, narrow bands which span all folia of the ipsilateral flocculus. The central band, 500-750 micrometer wide, projects to the medial vestibular nucleus, while the two adjacent bands, each 300-500 micrometer wide, innervate the superior vestibular nucleus. These three bands cover about one-half of the total area of the Purkinje cell layer of flocculus. Thus, the pattern of zonal projections in monkeys is the same as reported in rabbits and cats.

Animals↗

Organization of thalamic afferents to anterior dorsal ventricular ridge in turtles. I. Projections of thalamic nuclei.

Dorsal ventricular ridge (DVR) is a thalamorecipient, subcortical telencephalic structure in reptiles and birds. Although there is a fair amount of information about sources of afferents to DVR, little is known about the relationship of projections from individual thalamic nuclei to the organization of the structure. This study examines the relationship between thalamic projections and both areal and zonal divisions of anterior DVR (ADVR; Balaban, '78a) of emydid turtles with orthograde degeneration, autoradiographic and horseradish peroxidase techniques. Individual thalamic nuclei contribute either a diffuse or a restricted projection to ADVR. Diffuse projections arise primarily from the dorsomedial anterior nucleus. These fine-caliber axons distribute bilaterally over a wide region of the telencephalon via both medial and lateral thalamotelencephalic pathways. The terminal regions include septum, striatum and the medial bank of cortex caudal to the lamina terminalis. In ADVR, the fibers are distributed sparsely in zones 2-4 of dorsal, medial and ventral areas. Restricted projections to ADVR originate in nucleus rotundus, nucleus reuniens and nucleus caudalis. They ascend ipsilaterally in the lateral thalamotelencephalic pathway (lateral forebrain bundle), and enter ADVR rostral to the anterior commissure. Nucleus rotundus projects to zone 4 of dorsal area, nucleus caudalis projects to zones 2-4 of dorsal division of medial area, and nucleus reuniens projects to zones 2-4 of both the ventral division of medial area and the ventral area. Comparison of these results with thalamotelencephalic projections in mammals suggests that diffuse and restricted thalamic projection systems are a common feature of both groups. Restricted thalamic projections in reptiles, birds and mammals terminating in anatomically distinct regions, also appear to be associated with different sensory modalities. The significance of diffuse systems is not clear.

Afferent Pathways↗

Organization of thalamic afferents to anterior dorsal ventricular ridge in turtles. II. Properties of the rotundo-dorsal map.

This study describes some properties of the map of nucleus rotundus onto dorsal area of anterior dorsal ventricular ridge (ADVR) in emydid turtles by correlating results of anterograde and retrograde tracing experiments with observations from Golgi- and myelin-stained brains. An earlier paper (Balaban and Ulinski, '81) demonstrated that this projections is restricted to zone 4 of dorsal area of ADVR. This paper indicates that the rotundal pathway is organized such that longitudinally aligned groups of neurons in nucleus rotundus project to longitudinal regions in zone 4 of dorsal area. The projections field spans the dorso-ventral (or concentric) dimensions of zone 4 at each transverse level. Comparisons of experimental and Golgi preparations suggest that each rotundal neuron projects, via collaterals, to the entire rostrocaudal extent of rotundorecipient zone 4. Individual terminal branches span the dorsoventral dimension of zone 4 and are confined with both sagittal and transverse planes. Lesion experiments suggest that collaterals of a single rotundal axon are also distributed over at least one-third to one-half of the superficial-deep dimension of zone 4. This is also reflected in the observation that neurons from disjoint dorsal, dorsolateral and medial rotundal loci project to overlapping, concentric regions of dorsal area. Both this prominent concentric component of terminal branches and the extensive overlap is projections of neurons at distinct rotundal loci preclude the possibility of a topographic representation of either dorsoventral or mediolateral rotundal axes in zone 4 of dorsal area.

Animals↗

Evidence of a collateralized climbing fiber projection from the inferior olive to the flocculus and vestibular nuclei in rabbits.

In albino rabbits, horseradish peroxidase injections confined to vestibular nuclei retrogradely labeled neurons in the dorsal cap of the contralateral inferior olive. Mapping with stimulating electrodes revealed that stimulation of the lateral aspect of the medial vestibular nucleus and the medial aspect of the inferior vestibular nucleus evoked field potentials representing antidromic activation of contralateral dorsal cap neurons. These responses interfered with the antidromic response evoked from the contralateral flocculus and orthodromic responses evoked from the contralateral retina, suggesting that dorsal cap neurons which both receive retinal input and project to the flocculus send collaterals to vestibular nuclei.

Animals↗

Background and history of the interface between anxiety and vertigo.

The comorbidity of vertigo and anxiety has been an integral component of the medical literature since antiquity. In the works of Plato, the same terms were used in the context of vertigo, inebriation, height vertigo, disorientation, and mental confusion. In classical medicine, vertigo had the ambiguous status of being both a disease per se and a symptom of other diseases such as hypochondriacal melancholy. Further, two etiologies were described for vertigo: an origin in the head (brain) and an origin in the hypochondria (abdominal viscera). In the course of the development of a detailed neurologic taxonomy of vertigo in the latter half of the nineteenth century, a debate ensued whether agoraphobia was a form of vertigo or a distinct psychiatric condition. Elucidation of this forgotten debate, within its historical context, provides insights into the recent rediscovery of the balance-anxiety interface.

Agoraphobia↗