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Background The basement membrane (BM) provides mechanical shaping of tissues during morphogenesis. The Drosophila BM proteoglycan Perlecan (Pcan) is vital for this process in the wing imaginal disc. This function is thought to be fostered by the heparan sulfate chains attached to the domain I of vertebrate Pcan. However, this domain is not present in Drosophila, and the source of Pcan for the wing imaginal disc BM remains unclear. Here, we tackle these two issues. Results In silico analysis shows that Drosophila Pcan holds a domain I. Moreover, by combining in situ hybridization of Pcan mRNA and protein staining, together with tissue-specific Pcan depletion, we find that there is an autonomous and a non-autonomous source for Pcan deposition in the wing imaginal disc BM. We further show that both sources cooperate for correct distribution of Pcan in the wing imaginal disc and morphogenesis of this tissue. Conclusions These results show that Pcan is fully conserved in Drosophila, providing a valuable in vivo model system to study its role in BM function. The existence of two different sources for Pcan incorporation in the wing imaginal disc BM raises the possibility that inter-organ communication mediated at the level of the BM is involved in organogenesis. This article is protected by copyright. All rights reserved.

Prenatal methylazoxymethanol (MAM) administration at gestational day 17 has been shown to induce in adult rats schizophrenia-like behaviours as well as morphological and/or functional abnormalities in structures such as the hippocampus, medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc), consistent with human data.The aim of the present study was to further characterize the neurochemical alterations associated with this neurodevelopmental animal model of schizophrenia.We performed simultaneous measurements of locomotor activity and extracellular concentrations of glutamate, dopamine and noradrenaline in the mPFC and the NAcc of adult rats prenatally exposed to MAM or saline after acute systemic injection of a noncompetitive NMDA antagonist, MK-801 (0.1 mg/kg s.c.).A significant attenuation of the MK-801-induced increase in glutamate levels associated with a potentiation of the increase in noradrenaline concentrations was found in the mPFC of MAM-exposed rats, whereas no significant change was observed in the NAcc. MAM-exposed rats also exhibited an exaggerated locomotor hyperactivity, in line with the exacerbation of symptoms reported in schizophrenic patients after administration of noncompetitive NMDA antagonists.Given the importance of the mPFC in regulating the hyperlocomotor effect of NMDA antagonists, our results suggest that the prefrontal neurochemical alterations induced by MK-801 may sustain the exaggerated locomotor response in MAM-exposed rats.

Stress has been reported to disrupt the induction of synaptic plasticity in different fimbria target structures. The aim of the present study was to investigate whether chronic mild stress may also affect synaptic plasticity in the medial prefrontal cortex, a fimbria target structure. Fimbria tetanus (100 Hz) did not produce any changes in medial prefrontal cortex synaptic efficacy in non-stressed rats. Rats exposed to chronic mild stress, however, developed significant long-term potentiation. Treatment with fluoxetine (10 mg/kg, intraperitoneal) suppressed long-term potentiation induction in the chronic mild stress group. These data demonstrate that stress not only inhibits long-term potentiation development, as often demonstrated, but can also facilitate long-term potentiation development in certain brain circuits.

Both the habenula and the nucleus accumbens, and especially the glutamatergic innervation of the latter from the hippocampus, have been hypothesized to be involved, in different ways, in the pathophysiology of cognitive disturbances in schizophrenia. Lesions of the habenula produce disturbances of memory and attention in experimental animals. As the habenular nuclei have been shown to influence the release of many neurotransmitters, both in the hippocampus and the nucleus accumbens, we examined in this study the effects of bilateral habenula lesions on the plasticity of the fimbria-nucleus accumbens pathway, by means of the long-term depression phenomenon in freely moving rats. Long-term depression, induced within the shell region of the nucleus accumbens by low-frequency stimulation of the fimbria, was exaggerated and showed greater persistence in habenula-lesioned rats compared with sham-operated animals. These results indicate that plasticity in the fimbria-nucleus accumbens pathway is altered by habenula lesions in a way similar to previously-reported effects of stress and the psychosis-provoking agent ketamine. Moreover, they strengthen the views that the habenula belongs to systems, mediating higher cognitive functions, which involve the hippocampus and the nucleus accumbens. Finally, this study suggests that dysfunction of the habenula could contribute to cognitive alterations in diseases such as schizophrenia, where the habenula is reported to exhibit exaggerated calcification.

Excitatory glutamatergic fibers from limbic structures, such as the hippocampus and the basolateral amygdala, are known to converge on the same neurons in the nucleus accumbens. We have recently shown that ketamine, at a dose (25 mg/kg) that produces psychosis-like behaviors in rats, decreases glutamatergic transmission between the hippocampus and the nucleus accumbens. Here we investigated whether ketamine also affects glutamatergic transmission between the basolateral amygdala and the nucleus accumbens. We also studied the effects of amphetamine (1.5 mg/kg), known to evoke psychosis-like behaviors in rats. We found that each drug produced a long-lasting (at least 30 min) potentiation of synaptic efficacy in the projection from the basolateral amygdala to the nucleus accumbens. However, while this synaptic potentiation developed shortly after ketamine injection (within 4 min), it occurred after a 30-min delay in rats injected with amphetamine. These data reveal, in freely behaving rats, that ketamine has a more rapid and powerful effect on projection targets of the basolateral amygdala than does amphetamine.