Beta-amyloid(1-42)-induced cholinergic lesions in rat nucleus basalis bidirectionally modulate serotonergic innervation of the basal forebrain and cerebral cortex.

Ample experimental evidence suggests that beta-amyloid (A beta), when injected into the rat magnocellular nucleus basalis (MBN), impels excitotoxic injury of cholinergic projection neurons. Whereas learning and memory dysfunction is a hallmark of A beta-induced cholinergic deficits, anxiety, or hypoactivity under novel conditions cannot be attributed to the loss of cholinergic MBN neurons. As mood-related behavioral parameters are primarily influenced by the central serotonergic system, in the present study we investigated whether A beta(1-42) toxicity in the rat MBN leads to an altered serotonergic innervation pattern in the rat basal forebrain and cerebral cortex 7 days postsurgery. A beta infusion into the MBN elicited significant anxiety in the elevated plus maze. A beta toxicity on cholinergic MBN neurons, expressed as the loss of acetylcholinesterase-positive cortical projections, was accompanied by sprouting of serotonergic projection fibers in the MBN. In contrast, the loss of serotonin-positive fiber projections, decreased concentrations of both serotonin and 5-hydroxyindoleacetic acid, and decline of cortical 5-HT(1A) receptor binding sites indicated reduced serotonergic activity in the somatosensory cortex. In conclusion, the A beta-induced primary cholinergic deficit in the MBN and subsequent cortical cholinergic denervation bidirectionally modulate serotonergic parameters in the rat basal forebrain and cerebral cortex. We assume that enhanced serotonin immunoreactivity in the damaged MBN indicates intrinsic processes facilitating neuronal recovery and cellular repair mechanisms, while diminished cortical serotonergic activity correlates with the loss of the subcortical cholinergic input, thereby maintaining the balance of neurotransmitter concentrations in the cerebral cortex.

[Time-course of interocular alignment in arteficially esotropic cats]. / A szemtengely-beállítódás idóbeli lefolyása múvi kancsal macskákban.

Strabismus induced by eye-muscle surgery is a widely accepted experimental model of discordant binocular vision. Up to now, no attention was paid to the progress of strabismus in the postsurgical period, although, the grade of the developing strabismus is strongly influenced by the loss of binocularity in the visual system. Following lateral rectus laminotomy of 2-week-old kittens, the Hirschberg method and prisms were used to assess interocular alignment. The angle of deviation was measured weekly. During the first postoperative weeks, cats fixated still alternally, while by the end of the second postnatal month, when compared to healthy controls, operated cats were unable to align their eyes parallelly. They also showed persistent esotropy (+35 +/- 7 delta) that developed with a characteristic time-course. The interocular misalignment in artificially strabismic kittens develop gradually, and does not simply appear after the operation. The nature of this pathological process resembles the normal development of eye-movements in kittens, as well as in primate infants. Therefore, the surgery for strabismus in experimental animals at the earliest time point during the sensitive period are recommended, in order to provide ample time-window window for the effective development of the "strabismic visual system".

Postnatal development of unipolar brush cells in the cerebellar cortex of cat.

The postnatal developmental distribution pattern of metabotropic glutamate receptor (mGluR1a) immunoreactive unipolar brush cells (UBCs) was studied in the cerebellar cortex of kittens. On the day of birth (P0) UBCs are already present in the white matter in lobule X of the vermis, but only a few of these cell seemed to migrate to the deeper region of the internal granular layer. By the end of the first week (P8) UBCs were seen to invade the white matter + internal granular layer of lobules IX, VIII, I, and II of the vermis, and they spread further in the transitory area medio-laterally from the vermis toward the cerebellar hemispheres. By P15, UBCs appeared in lobules III and VII of the vermis, as well as in corresponding lobules of the neocerebellum, with especially high numbers in lobule VII. By P22, UBCs migrated further after their medio-lateral course in the neocerebellum, and began to invade lobules V and VI. At P62 the amount of UBCs in midsagittal planes of early developing vermal lobules (I, II, VII-X) resembled the P132 or adult pattern. The medio-lateral migration and incorporation of UBCs into the late-developing cerebellar lobules V and VI was completed only by P132, when the spatial distribution of UBCs in both the vermal and neocerebellar lobules was comparable to that seen in the 1 year old young adult cat. Although by P132 the postnatal migration of the vast majority of UBCs seemed to be completed, in the cerebellum of adult cats a few migrating UBCs could still be observed in the white matter of the cerebellar lobules, and beneath the ependyma of the fourth ventricle. It is concluded that during ontogenesis the migration course of UBCs follows essentially the developmental sequence of cerebellar lobules, although the incorporation of UBCs into the internal granular layer continues until 4 months postnatally, i.e., much beyond the apparent completion (about two months postnatally) of cytoarchitectonic built up of the cerebellar cortex of kittens.

Immunocytochemical mapping of NPY and VIP neuronal elements in the cat subcortical visual nuclei, with special reference to the pretectum and accessory optic system.

The aim of this study was to describe the distribution patterns of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) neuronal elements in subcortical visual centers of the cat. Numerous NPY-ir neurons were present in the feline nucleus of the optic tract and in the anterior pretectal nucleus. Only a few NPY-ir neurons were found in the posterior, medial and olivary pretectal nuclei and in the accessory optic nuclei. Diffuse and heavily beaded NPY-ir fiber plexuses were observed throughout the superior colliculus, pretectum, and accessory optic system. Extensively arborising NPY-ir fibers were present in the mesencephalon and ventral lateral geniculate nucleus, while the dorsal visual thalamic nuclei contained only a few NPY-ir fibers. VIP-ir cells were present mainly in the accessory optic nuclei, and they were absent in the dorsal visual thalamus. Both NPY- and VIP-ir neurons were multipolar and fusiform in shape in the regions studied. Enucleation did not alter the appearance of NPY- and VIP-containing neuronal elements in the superior colliculus and pretectum while in the thalamus a subset of NPY-ir fiber population disappeared, indicating their retinal origin. Although there is a partial overlap in the topographical localization of the NPY- and VIP-ergic neurons in the pretectum, the colocalization of the two peptides could not be demonstrated. The present observations demonstrate the existence of two different and separate peptidergic (NPY and VIP) neuronal populations in the pretectum.

Metabotrop glutamate receptor type 1a expressing unipolar brush cells in the cerebellar cortex of different species: a comparative quantitative study.

Morphology, distribution and number of unipolar brush cells (UBCs) was studied in the cerebellar vermal lobules I-X of the chicken, rat, guinea pig, cat, and monkey using monoclonal mGluR1a antibody as a marker to visualise these recently described nerve cells (Mugnaini and Floris [1994] J. Comp. Neurol. 339:174-180; Mugnaini et al. [1994] Synapse 16:284-311). The morphological appearance of mGluR1a immunopositive UBCs is similar in all species investigated: they are small cells, having a single, relatively short and thick dendrite, terminating in brush-like dendrioles. Although this, probably excitatory, cell type can be found all over the cerebellar cortex, highest density of UBCs can be seen in the vermal cortex. The present study, therefore, was focused on the quantitative morphology and distribution of UBCs in the 10 lobules of the vermis. Calculating the number of UBCs/l Purkinje cell (PC), we have found differences in this value (average in vermal lobules I-X) from 1.04 in rat, 1.10 in chicken, 1.16 in guinea pig, 2.27 in monkey, and up to 2.44 in cat. The highest density of UBCs was observed in lobules I, IX, and X, whereas the lowest number of UBCs/l PC was found in lobules IV-VI (in the mammals) and in lobules VII-VIII (in the chicken). In mammals, particularly the monkey and cat, an increased presence of UBCs was observed in vermal sub-lobules VIc-VIIb,c, a region defined as the oculomotor vermis because of its role in the control of saccadic eye movement. There is also a basic difference between chicken and mammals in the distribution of UBCs within the lobules: in mammals, the lowest density of these nerve cells was found in the peripheral portion of the lobules, near to the pia, while in the chicken, in contrast, the density of UBCs was the highest subpially with fewer UBCs located in the deepest curvature of the lobules. Finally, the functional significance of the differences in the density and in the distribution pattern of UBCs in the cerebellar vermis between the phylogenetically different species investigated is briefly discussed.

Light and electron microscopic analysis of synaptic input from cortical area 17 to the lateral posterior nucleus in cats.

The morphology and synaptic organization of the corticothalamic (CT) fibres from area 17 were studied in the lateral posterior nucleus (LP) of the thalamus in cats. Injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL) into primary visual cortex labelled a band of CT fibres in the LP with terminal field confined to its lateral division "LP1". PHAL-labelled CT axons in the LP1 gave rise to both en passant and terminal boutons. They usually established several synaptic contacts--often in complex glomerulus-like synaptic arrangements--with dendritic shafts of large diameter and presynaptic dendrites containing pleomorphic vesicles. Postsynaptic targets of the PHAL-labelled CT boutons were characterized by postembedding gamma-aminobutyric acid (GABA) immunocytochemistry. It appeared that, in the LP1 of the cat, almost half (44.5%) of the postsynaptic dendrites to CT boutons from area 17 belonged to the GABA-immunopositive interneurons and the majority (41%) of these GABA-immunopositive dendrites were F2 terminals. These results indicate that the CT axons from the striate cortex in the LP of the cat, in addition to a direct excitatory action, exert a powerful feed-forward inhibition on the thalamic principal cells.