In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-Daspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population.The main function of oligodendrocytes is to myelinate axons in the vertebrate central nervous system. This cell type develops mostly soon after the majority of neurons are generated and have extended their axons and, therefore, it is likely that neurons play an important role in regulating oligodendrocyte development. In the rat optic nerve, the first fully differentiated oligodendrocytes appear after birth, and the definitive mature population of oligodendrocytes is reached around 6 weeks later (1, 2). The proliferation and the survival of oligodendrocytes depend, respectively, on the electrical activity of neighboring axons and in the reciprocal contacts they establish (for a recent review, see ref.3). Axon to oligodendrocyte signaling results in the generation of the precise number of oligodendrocytes necessary to myelinate entirely a given population of axons. Unfortunately, little information is available about the molecules participating in this signaling process.Oligodendrocytes express neurotransmitter receptors including those activated by glutamate (4). This excitatory amino acid acts at various types of receptors, which can be grouped into two major categories: ionotropic receptors, which gate membrane ion channels permeable to cations; and metabotropic receptors, which are coupled to G proteins. Ionotropic receptors are classified into ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-Daspartate (NMDA) subtypes, according to their preferred agonist. Molecular cloning has revealed that each receptor subtype is composed of several subunits with high homology within each receptor class (reviewed in ref. 5). Thus, AMPA receptors are formed by GluR1-4, kainate receptors by GluR5-7 and KA1-2, and NMDA rece...

The system of tangential connections was studied in area 17 of normally reared (NR), binocularly deprived (BD) and dark-reared (DR) kittens and adult cats. Connections were labelled antero- and retrogradely by intracortical micro-injections of several fluorescent markers and horseradish peroxidase conjugated with wheat-germ agglutinin (WGA-HRP). In 5-day-old kittens tangential connections consist of homogeneously distributed fibres extending maximally over 2.7 mm. Around postnatal day (pnd) ten these connections start to express the patchy pattern characteristic of the adult. Retrogradely stained somata and anterogradely labelled terminals become organized in individual 300 to 350 microm wide clusters with a centre-to-centre spacing of about 500 microm. During the first three postnatal weeks the horizontal connections increase their span to up to 10.5 mm and the spacing between individual patches increases to about 700 microm. Over the following 4 weeks these projections become reduced in length and number. In adult NR cats, tangential connections span a distance of up to 3 mm and form a lattice of 200 - 500 microm wide clusters, which have an average centre-to-centre spacing of 1050 microm. Tangential connections originate and terminate in all cortical laminae except layer I and they are organized in register. The distances spanned are largest in supragranular, intermediate in infragranular and shortest in granular layers. In BD and DR cats older than 10 weeks, the length of intracortical tangential fibres becomes reduced to the same extent as in NR animals, but individual clusters are less numerous. The authors conclude that the lattice-like structure of lateral connections evolves independently of visual experience, and that the selectivity of interactions results from pruning of initially exuberant connections. It is suggested that this pruning process is dependent on activity and influenced by visual experience.

The expression of brain derived neurotrophic factor (BDNF) and its preferred receptor (TrkB) in rat retinal ganglion cells (RGCs) have been determined in the present study. To identify RGCs retrograde labelling was performed with fluorogold (FG). Subsequently, retinas were immunostained with antibodies to BDNF and TrkB. We found that all RGCs labelled with FG express both BDNF and its preferred receptor, TrkB. Moreover, displaced amacrine cells were also found to be immunolabelled by both antibodies. Thus BDNF/TrkB signalling in RGCs probably involves endogenous BDNF produced by the RGCs themselves.

New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB.