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Macrophage inflammatory protein-1 (MIP-1) evokes an intense fever, independent of a prostaglandin mechanism, and is now thought to play an important role in the defence response to bacterial pyrogens. The purpose of this study was 2-fold: (i) to determine whether the potent doublet of this cytokine, MIP-1beta, is actually produced in the brain in response to a pyrogenic dose of a lipopolysaccharide of Escherichia coli and (ii) to determine the anatomical site of synthesis of this cytokine in the brain. Following the intense fever produced by intraperitoneal administration of lipopolysaccharide in the unrestrained rat, MIP-1beta immunoreactivity was identified post mortem in two regions of the brain implicated in fever: the organum vasculosum laminae terminalis (OVLT) and the anterior hypothalamic, preoptic area (AH/POA). Microinjection of goat anti-mouse MIP-1beta antibody (anti-MIP-1beta) directly int the AH/POA markedly suppressed fever in rats in response to lipopolysaccharide. Further anti-MIP-1beta administered 180 min after the injection of lipopolysaccharide acted as an antipyretic and reversed the fever induced by the endotoxin. anti-MIP-1beta or control immunoglobulin G antibody microinjected into the hypothalamus immediately before the intraperitoneal injection of the control saline did not alter the temperature of the rats. Taken together, the present results demonstrate that MIP-1beta is produced in the brain in response to a bacterial endotoxin. These observations, in the light of earlier data on fever induced by MIP-1beta, further support the hypothesis that endogenously synthesized MIP-1beta acts as an intermediary factor in the evocation of fever by acting on the thermosensitive cells of the brain.

The presence of ipsilateral inferior olivary neurons during postnatal development of the olivocerebellar projection in the rat was investigated by two in vitro axonal tracing methods and by the axotomy of one olivocerebellar tract. The experiments were carried out before (P1), during (P5–P10) and after (P20) the period of multiple innervation of Purkinje cells by climbing fibers. According to present results: (1) ipsilateral inferior olivary neurons are distributed, on all analyzed days, throughout the entire inferior olive; (2) cell counts after axotomy experiments demonstrated that they represent a small population of inferior olivary neurons, whose number oscillated between 271 ± 30 in young animlas (pedunculotomized at P1 and killed at P7) and 26 ± 12 in older ones (pedunculotomized at P20 and killed at P40). This experiment confirmed that most of these neurons are eliminated during the regressive events that take place during normal development of the olivocerebellar projection; and (3) few ipsilateral inferior olivary neurons, however, survive at P40, but their significance is still unclear. © 1994 Wiley-Liss, Inc.

The membrane properties of the neurons located in the ventral part of the periaqueductal grey (PAG) of the guinea-pig were studied using an in vitro slice preparation. Cells had low values of resting membrane potential (-53.3 +/- 1.3 mV, mean +/- standard error), high input resistance (195. +/- 16.2 M ohm) and moderate values of membrane time constant (12.6 +/- 0.7 ms). The last two parameters changed as recordings were made along the sagittal axis, higher values corresponding to the more rostral cells. Three main neuronal types-fusiform, triangular and stellate-were found in the ventral PAG using intracellular injection of Lucifer yellow. A study of the cell number and cell density was carried out in coronal and sagittal sections of the ventral PAG. This analysis showed a clear gradient of size in this region arising from the gradual disappearance of large (17 to 40 microm) neurons in the caudorostral direction. The neuronal density also increased in this direction. Therefore, some electrotonic and morphological parameters differ along the sagittal axis. These findings suggest a larger neuronal heterogeneity of the caudal part of the PAG, and might contribute to a functional segregation of this region.

The retina of the chick contains retinal cells of a morphology very similar to that of the horizontal cells, but the perikarya, axons, and axon terminals lie in the inner plexiform layer. The discovery of this neuronal ectopia appears to support the idea that some horizontal and amacrine cells derive from a common, freely migrating cell.

This paper examines the organization of host afferents within cerebellar grafts implanted into kainic acid lesioned cerebellum. Our selection of a cerebellum, a prime example of a 'point-to-point' system, permits precise determination of the degree and the specificity of host-graft interactions. One month after a cerebellar injection of kainic acid, the lesion produced can be divided into two concentric regions: (i) a central necrotic zone, totally depleted of neurons (zone 1), and (ii) a peripheral zone which lacks all Purkinje cells but preserves its cortical lamination (zone 2). Two months after the implantation of solid pieces of embryonic cerebellum, the graft has evolved into a minicerebellar structure, occupying most of zone 1. The grafted minicerebellum consists of a highly convoluted trilaminated cortex with a core containing deep nuclear neurons. Purkinje cells are positioned between the molecular and granular layer with their short and irregular dendrites branching within the former. Donor foetal Purkinje cells migrate into the contiguous portion of the molecular layer of the host zone 2. These embryonic neurons set up within the upper three-quarters of the host molecular layer, and develop monoplanar dendritic trees that span the whole width of the layer. The organization of host-graft interactions was studied by autoradiography of anterogradely transported tritiated leucine, injected in the host bulbar region containing the caudal half of the inferior olivary complex (origin of all vermal climbing fibres) and the dorsally adjacent paramedian reticular nucleus (origin of a few mossy fibres). Numerous labelled fibres cross the host-graft interface from the white matter of the host cerebellum, and provide innervation to the minicerebellar structure. The vast majority of these labelled axons terminate in the molecular layer, forming axonal arborizations that follow the shape of the Purkinje cell dendrites. The labelled climbing fibres are organized into uneven sagittally aligned strips, which mimic that of olivocerebellar projections in control rats. Only a small proportion of host labelled fibres end in the donor granular layer, forming typical mossy fibre rosettes. The latter are present in the region of the graft close to the host-graft interface. In addition, labelled axons are observed climbing over the dendritic trees of grafted Purkinje cells that have invaded a portion of the host molecular layer of zone 2. In all regions containing grafted Purkinje cells and labelled climbing fibres, the density of the innervation is close to normal with practically all Purkinje cells receiving a climbing fibre. The extensive integration of the grafted cells into the deficient neuronal networks of the host clearly illustrates the positive neurotropic effect exerted by immature cerebellar neurons on adult extracerebellar afferent fibres. The hodological integration, allowing a possible restoration of the impaired cerebellar circuitry, takes place respecting the specificity and topographic distribution which characterize the 'point-to-point' arrangement of normal cerebellar circuitry.