Cerebellar contribution to spatial event processing: Morris water maze and T-maze.

Recently, a cognitive function of cerebellar networks has been challenging the traditional view of the cerebellum as a motor control centre. Among the cognitive abilities reported to be affected by cerebellar deficits is the capacity to solve a spatial problem. We investigated the influence of a cerebellar lesion on spatial abilities by behavioural analysis of rats that had undergone surgical hemicerebellectomy (HCb; HCbed rats). Experiments were performed with a Morris water maze (MWM) and a water T-maze in both cue and place versions (visible or hidden platform respectively). Results indicate a severe impairment in coping with spatial information in all phases of MWM testing as well as in the T-maze paradigm. However, if the MWM cue phase was prolonged, HCbed rats displayed some ability to learn platform position, although at a level significantly different from controls. They succeeded in finding the platform, even in a pure place paradigm, such as finding a hidden platform with the starting points sequentially changed. Retention testing was also performed, demonstrating that HCb affects acquisition but not retention of spatial information. HCbed animals exhibit such disrupted exploration behaviour that they can display only peripheral circling, and they can acquire spatial relations only when proximal cues are available. Furthermore, in all phases of testing, platform finding for HCbed animals is essentially based on place strategies. Thus, a specific pattern of spatial behaviour, markedly different from that displayed following hippocampal or cortical lesions, characterizes cerebellar lesioned rats. These results are discussed taking into account the role in procedural learning recently assigned to cerebellar networks, demonstrating that the cerebellar circuits represent the keystone of the procedural components of spatial event processing.

Subdivisions of macaque monkey auditory cortex revealed by calcium-binding protein immunoreactivity.

The aim of this investigation was to characterize auditory areas of the primate cerebral cortex on the basis of chemoarchitecture. Cortical areas of the supratemporal plane were delineated in Macaca fuscata (M. fuscata) by immunocytochemical staining for parvalbumin, staining for cytochrome oxidase, examination of cyto- and myeloarchitecture, and retrograde tracing of corticocortical connections. Comparative observations were made on Macaca fascicularis (M. fascicularis). Differential staining of fiber plexuses, probably of thalamic origin, identifies a central core zone of dense immunostaining and a surrounding zone of moderate-to-dense immunostaining composed of anteromedial, lateral, and posteromedial fields. Outside the second zone, there is a third anterolateral zone of weaker immunoreactivity, and, outside that zone, there is a fourth zone in which immunoreactivity is virtually absent. Differences in parvalbumin immunostaining in the auditory fields may reflect differences in relative contributions of thalamic inputs from parvalbumin-immunoreactive cells in the medial geniculate complex. The central core zone and the surrounding three fields can be correlated with major auditory fields previously defined by multiunit mapping and thalamocortical connectivity. The core zone contains a large principal field and an anterior extension. The pattern of corticocortical connections between these and adjoining fields suggests that the anteromedial, lateral, and posteromedial fields represent first steps in three streams of connections passing outward from auditory into association cortex. M. fuscata has an unusually large auditory cortex that is more deeply placed in the lateral sulcus in comparison to that of M. fascicularis. A small annectant gyrus provides a guide to the position of the primary auditory area.

Auditory thalamocortical pathways defined in monkeys by calcium-binding protein immunoreactivity.

This study investigated differentiation of Macaca fuscata auditory thalamus into chemically defined nuclei forming relays to auditory cortical areas. The thalamus was stained immunocytochemically for parvalbumin and 28 kDa calbindin in normals and in brains in which retrogradely transported tracers were injected into middle layers of auditory cortical areas or applied to the cortical surface. Parvalbumin- and calbindin-immunoreactive cells show a complementary distribution in ventral, anterodorsal, posterodorsal, and magnocellular medial geniculate nuclei. The ventral nucleus has a high density of parvalbumin cells and few calbindin cells, and the anterodorsal nucleus has a high density of parvalbumin cells and moderate numbers of calbindin cells. Both nuclei have a dense parvalbumin-immunoreactive neuropil formed by terminations of fibers ascending in the brachium of the inferior colliculus. The posterodorsal nucleus has approximately equal proportions of parvalbumin and calbindin cells; neuropil staining is weak but contains terminations of calbindin-immunoreactive fibers ascending in the midbrain tegmentum. The magnocellular nucleus contains domains of parvalbumin and calbindin cells. Parvalbumin cells in the ventral nucleus project to a central core of auditory cortex with densest parvalbumin immunoreactivity. Those in anterodorsal and posterodorsal nuclei project to surrounding auditory fields with less dense parvalbumin immunoreactivity; those in the magnocellular nucleus project widely to auditory and other fields. Injections of middle cortical layers label a large majority of parvalbumin cells in the ventral, anterodorsal, or posterodorsal nuclei and in the magnocellular nucleus. Superficial deposits label calbindin cells only, usually in more than one nucleus, implying a widespread projection system.

Transient changes in Fos and GFAP immunoreactivity precede neuronal loss in the rat hippocampus following neonatal anoxia.

Early and delayed neuronal and glial changes in the hippocampus were studied in Wistar rats following neonatal anoxia induced by 100% N2 exposure for 25 min at approximately 30 h postnatally. Sham-treatment induced a transient increase in the number of fos immunoreactive neurons in the CA1, CA2, and CA3 regions, with a peak at 120 min following handling. In contrast, a significant decrease in the number of fos-stained cells was seen in the CA1 and CA2 regions at 120 min after the exposure to anoxia, compared to sham-treatment. At 150 and 240 min increased fos immunoreactivity was detected in the CA2 region of anoxic rats. Enhanced glial fibrillary acidic protein staining was seen at Postnatal Day 7 (P7) in the hippocampus of the rats exposed to neonatal anoxia, while no differences between anoxic and sham-treated animals were observed at later time-points. No alteration in nerve cell density was found at P7, while at P15 and later stages a significant reduction in neuronal density was seen in the CA1 region of anoxic rats. Thus, the rapid induction in hippocampal neuronal activity that followed sham-treatment was blocked by the neonatal anoxia, as revealed by changes in immediate early gene expression. A transient reactive astrocytosis developed in the days after the anoxic insult, followed by a loss of neurons in the CA1 region. The findings indicate that a sequence of specific neuronal and glial alterations takes place in the hippocampus after neonatal anoxia, which finally leads to a detectable, regionally restricted, neuronal loss. Moreover, inhibition in fos protein expression may be an early marker for the anoxic damage in CA1 neurons.

Chemical compartmentation and relationships between calcium-binding protein immunoreactivity and layer-specific cortical caudate-projecting cells in the anterior intralaminar nuclei of the cat.

Neurons projecting to the parietal cortex or striatum and neurons showing immunoreactivity for the calcium-binding proteins parvalbumin and 28KD-calbindin were examined in the anterior intralaminar nuclei (IL) of the cat. Retrograde tracing from deep or superficial parietal cortical layers or from the caudate nucleus was coupled with immunohistochemistry to determine which of these proteins were expressed in the projection neurons. It was found that IL neurons project to deep as well as to superficial layers of the parietal cortex, that IL-cortical neurons could be differentiated into two populations according to their cortical projection pattern and their soma size, and that IL neurons projecting to the parietal cortex or to the striatum express 28KD calbindin immunoreactivity but not parvalbumin immunoreactivity. The distribution of immunoreactivity to 28KD calbindin and parvalbumin in the neuropil showed a consistent complementary distribution pattern in the IL. The compartments based on differential parvalbumin and 28KD calbindin expression may indicate the presence of functionally segregated units in IL.

Vestibular compensation is affected by treatment with dopamine active agents.

The aim of the present work was to examine the effects of postoperative treatments with agents active on dopaminergic system on vestibular recovery from the postural and ocular symptoms which follow a unilateral labyrinthectomy. Hemilabyrinthectomized guinea pigs were given a daily i.p. injection of bromocriptine (1 mg/kg) or sulpiride (10 mg/kg) or lisuride (0.1 mg/kg) or saline from post-operative days 1 to 21. Treatment with bromocriptine, a D2 agonist, accelerates compensation of postural and ocular symptoms. Conversely, treatment with sulpiride, a D2 antagonist, slows down the reachievement of symmetrical posture and stable ocular motility. Finally, the lisuride treatment, a drug active on D2 but also on other monoaminergic receptors, delays vestibular recovery so markedly to reach a "freezing" of vestibular deficits during drug treatment. These findings indicate that the already demonstrated role of dopamine in motor activity and learning can be extended to the learning processes required to recover from vestibular asymmetries.

Development of monoamine systems after neonatal anoxia in rats.

Neurochemical and morphological effects of neonatal anoxia on monoamine systems were studied after 100% N2 exposure for 25 min at 30 h postnatally (postnatal day 2-P2). At 20 min after anoxia, reductions of tissue levels of cerebellar noradrenaline (NA) and striatal dopamine (DA) and metabolites were seen, while 5-hydroxyindoleacetic acid (5-HIAA) was increased in cortex and cerebellum. At P7, NA increased in cerebellum, while serotonin (5-HT) and 5-HIAA decreased in cortex and cerebellum. At P21, increased hippocampal NA and striatal homovanillic acid (HVA) were found, while striatal 5-HT decreased and 5-HIAA increased in striatum and hippocampus. At P60, striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-HIAA levels were found to be enhanced. No effects were seen on 5-HT, tyrosine hydroxylase, or DARPP-32 immunostaining in cortex, hippocampus, and striatum. Thus, the neonatal anoxia induced both acute and persistent neurochemical abnormalities in monoamine systems that were not accompanied by morphological changes detectable with the methods used. The monoamine alterations found could be critically connected to the behavioral disturbances observed in rats after neonatal anoxia. The findings may also be of relevance to dysfunctions seen in humans after perinatal oxygen deficiency, e.g., the attention deficit hyperactivity disorder syndrome.

Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats.

Physical and reflex development, spontaneous behavior in open field and spatial memory abilities have been studied in rats after neonatal anoxia. Histological analysis of the hippocampal fields have been carried out in selected animals at the end of the testing period. No differences between control and anoxic rats were recorded in the physical and reflex development. Hyperactivity in open field was present in anoxic animals only transiently between P20 and P45. Spatial memory abilities, tested at two developmental stages by means of a maze and a water maze, appeared to be defectual not only during the hyperactivity period but also in adulthood. The histological analysis of the different hippocampal fields demonstrated a significant difference between anoxic and control rats in the cell density of the CA1 field. The present data demonstrate that neonatal anoxia, besides determining only transitory defects in open field behavior, profoundly affects cognitive abilities and cell density in CA1 hippocampal field. These results might be of relevance in the interpretation of the substrate of the cognitive impairment seen in hyperactive children that are exposed to hypoxia at birth.