Neuroscience
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The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells. ⋯ We report opposing, layer-specific effects of VEGF-D knockdown which resulted in shrinkage of basal and increased complexity of apical dendrites. Synaptic potentials and layer-specific voltage gradients during network oscillations remained, however, unaltered. These findings reveal a high spatial selectivity of VEGF-D effects at the sub-cellular level, and strong homeostatic mechanisms which keep spatially segregated synaptic inputs in a balance.
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Understanding how the brain decodes sensory information to give rise to behaviour remains an important problem in systems neuroscience. Across various sensory modalities (e.g. auditory, visual), the time-varying contrast of natural stimuli has been shown to carry behaviourally relevant information. However, it is unclear how such information is actually decoded by the brain to evoke perception and behaviour. ⋯ Further analysis revealed that the lower detection thresholds of midbrain neurons were not due to increased sensitivity to the stimulus. Rather, these were due to the fact that midbrain neurons displayed lower variability in their firing activities in the absence of stimulation, which is due to lower firing rates. Our results suggest that midbrain neurons play an active role towards enabling the detection of weak stimulus contrasts, which in turn leads to perception and behavioral responses.
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The effects of systemic inflammation on the pathogenesis of Alzheimer's disease (AD) are not clarified, both beneficial and deleterious effects being reported. Allergy is accompanied by a systemic inflammatory response and some epidemiological studies have reported a positive association between a history of allergy/asthma and dementia. To investigate whether chronic airway allergy influences the inflammatory status in the brain, AD-like pathology, and behaviour in relation to AD, we induced chronic airway allergy in triple transgenic AD (3xTgAD) and wildtype (WT) mice by repeated exposure to ovalbumin (OVA) as allergen. ⋯ In contrast, allergy increased the levels of interleukin (IL)-1β and complement component 1q (C1q) in WT mice. Bronchoalveolar lavage fluid analysis confirmed eosinophilia in both genotypes, but the basal levels of eosinophils were lower in 3xTgAD mice. In summary, allergy induced predominantly anti-inflammatory effects in 3xTgAD mice, and pro-inflammatory effects in WT mice, thus being another potential factor to be considered when studying AD pathogenesis.
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The integrity of the perirhinal cortex (PRh) is essential for object recognition memory (ORM) function, and damage to this brain area in animals and humans induces irreversible ORM deficits. Here, we show that activation of area V2, a brain area interconnected with brain circuits of ventral stream and medial temporal lobe that sustain ORM, by expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14414) restored ORM in memory-deficient PRh-lesioned rats and nonhuman primates. ⋯ Thus, RGS14414-mediated activation of area V2 has therapeutic relevance in the recovery of recognition memory, a type of memory that is primarily affected in patients or individuals with symptoms of memory dysfunction. These findings suggest that area V2 modulates the processing of memory-related information through activation of interconnected brain circuits formed by the participation of distinct brain areas.
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Caveolin-1 (Cav-1) is an important modulator for adult neurogenesis in post stroke brain repair but its underlying mechanisms are largely unknown. In the present study, we report that endothelial Cav-1 inhibits neuronal differentiation of neural stem/progenitor cells (NSCs/NPCs) in post ischemic brain via regulating vascular endothelial growth factor (VEGF) and NeuroD1 signaling pathway. We first investigated the dynamic change of Cav-1 and its impact on neuronal differentiation in rat and mouse models of 2 h transient middle cerebral artery occlusion (MCAO) plus 1, 7, 14, 21 and 28 day of reperfusion. ⋯ The major discoveries include: (1) Cav-1 expression in the hippocampal dentate gyrus (DG) was down-regulated on day 1 after 2 h cerebral ischemia, and gradually recovered with reperfusion time, accompanied with transient increased but gradually reduced neuronal differentiation of NPCs marked by doublecortin (DCX). (2) Cav-1 knockout mice exhibited the increased DCX and VEGF at the granular cell layers of hippocampal DG in post-ischemic brains. (3) Co-cultured with BMVECs, NPCs had remarkably decreased neuronal differentiation under OGD/R. Knockdown of Cav-1 in the BMVECs increased VEGF secretion into the medium and NeuroD1+ cells, and rescued the neuronal differentiation of NPCs without affecting astroglial and oligodendroglial differentiation. (4) Cav-1 exosomes released from BMVECs inhibited neuronal differentiation of NPCs via decreasing the expression of VEGF, p44/42MAPK phosphorylation and NeuronD1 upon OGD/R insults. Taken together, endothelial Cav-1 serves as a niche regulator to inhibit neuronal differentiation via negatively modulating VEGF, p44/42MAPK phosphorylation and NeuronD1 signaling pathway.