Neuroscience
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Perineuronal nets (PNNs) are specialized substructures of the neural extracellular matrix (ECM) which envelop the cell soma and proximal neurites of particular sets of neurons with apertures at sites of synaptic contact. Previous studies have shown that PNNs are enriched with chondroitin sulfate proteoglycans (CSPGs) and hyaluronan, however, a complete understanding of their precise molecular composition has been elusive. In addition, identifying which specific PNN components are critical to the formation of this structure has not been demonstrated. ⋯ Lastly, we determined that while all PNN components are bound to the surface in a hyaluronan-dependent manner, only HAPLN1 remains attached to the cell surface when neurons are treated with chondroitinase. These results suggest a different model for the molecular association of PNNs to the cell surface. Together our work has served to assess the contribution of aggrecan to PNN formation while providing key evidence concerning the molecular composition of PNNs in addition to determining how these components ultimately form PNNs.
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Noradrenaline, essential for the modulation of memory, is released in various parts of the brain from nerve terminals controlled by the locus coeruleus (LoC). Noradrenaline release consequent upon input from higher brain areas also occurs within the LoC itself. We examined the effect of noradrenaline on adrenergic receptors in the LoC on memory processing, using colored bead discrimination learning in the young domestic chick. ⋯ This interpretation is supported by the actions of noradrenaline uptake blockers that produce the same memory outcome. BRL44408 in the mesopallium also caused memory enhancement. β2-ARs are important in the first time window, whereas α1-, α2C-and β3-ARs are important in the second time window. The results reveal that for successful memory formation noradrenaline release is necessary within the LoC as well as in other brain regions, at the time of consolidation of memory from short-term to intermediate and from intermediate to long-term memory.
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D2 and D4 dopamine receptors play an important role in cognitive functions in the prefrontal cortex and they are involved in the pathophysiology of neuropsychiatric disorders such as schizophrenia. The eventual effect of dopamine upon pyramidal neurons in the prefrontal cortex depends on which receptors are expressed in the different neuronal populations. Parvalbumin and calbindin mark two subpopulations of cortical GABAergic interneurons that differently innervate pyramidal cells. ⋯ Parvalbumin cells mainly expressed D4 mRNA (65%) and less D2 mRNA (15-20%). Finally, calbindin cells expressed both receptors in similar proportions (37%). We hypothesized that D4 receptor could be a complementary target in designing new antipsychotics, mainly because of its predominance in parvalbumin interneurons.
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Astrocytes are the predominant glial-cell type in the CNS and they are known to play an active role in modulating neuronal function. Since many of the same molecules including G-protein coupled receptors (GPCRs) are expressed in both neurons and astrocytes, in vivo pharmacological manipulations to target astrocytes lack specificity. In this study, we investigated the effect of Pleckstrin Homology (PH) domain of Phospholipase C (PLC)-like protein p130 (p130PH) on Ca(2+) signaling in astrocytes in vivo. ⋯ Our results show that mRFP-p130PH is exclusively expressed in astrocytes with a high efficiency and a stable expression level. In vivo imaging using two-photon microscopy demonstrated reduced Ca(2+) signal in transduced astrocytes in response to ATP stimulation. As Ca(2+) signaling is a characteristic form of cellular excitability in astrocytes that can mediate chemical transmitter release and contribute to neuronal excitotoxicity, the current study provides an in vivo approach to better understand Ca(2+)-dependent gliotransmission and its involvement in glia-related diseases.
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PKC-theta (PKC-θ), a member of the novel protein kinase C family (nPKC), regulates a wide variety of functions in the periphery. However, its presence and role in the CNS has remained largely unknown. Recently, we demonstrated the presence of PKC-θ in the arcuate hypothalamic nucleus (ARC) and knockdown of PKC-θ from the ARC protected mice from developing diet-induced obesity. ⋯ Double-label immunohistochemisty in mice expressing green fluorescent protein either with the long form of leptin receptor (LepR-b) or in orexin (ORX) neurons indicated that PKC-θ is highly colocalized in lateral hypothalamic ORX neurons but not in lateral hypothalamic LepR-b neurons. Double-label immunohistochemistry in oxytocin-enhanced yellow fluorescent protein mice or arginine vasopressin-enhanced green fluorescent protein (AVP-EGFP) transgenic rats revealed a high degree of colocalization of PKC-δ within paraventricular and supraoptic oxytocin neurons but not the vasopressinergic neurons. We conclude that PKC-θ and -δ are expressed in different hypothalamic neuronal populations.