Hippocampus
-
Motivated by the synaptic tagging and capture (STC) hypothesis, it was recently shown that a weak learning, only able to produce short-term memory (STM), can succeed in establishing long-term memory (LTM) with a concomitant, stronger experience. This is consistent with the capture, by the first-tagged event, of the so-called plasticity-related proteins (PRPs) provided by the second one. Here, we describe how a concomitant session of reactivation/reconsolidation of a stronger, contextual fear conditioning (CFC) memory, allowed LTM to result from a weak spatial object recognition (wSOR) training. ⋯ Furthermore, either a Water Maze reconsolidation, or a CFC extinction session, allowed the formation of wSOR-LTM. These results suggest for the first time that a reconsolidation session can promote the consolidation of a concomitant weak learning through a probable STC mechanism. These findings allow new insights concerning the influence of reconsolidation in the acquisition of memories of otherwise unrelated events during daily life situations.
-
Chronic stress and depression are associated with decreased levels of hippocampal neurogenesis. On the other hand, antidepressants as well as environmental enrichment may rely in part on their pro-neurogenic effects to improve cognition and mood. Because a functional heterogeneity has been consistently reported along the septo-temporal axis of the hippocampus, regional changes in neurogenesis could differentially contribute to these effects and affect distinct hippocampal functions. ⋯ Whereas fluoxetine treatment in control mice affected proliferation and survival specifically in the temporal hippocampus, it reversed most of the UCMS-induced alterations all along the septo-temporal axis. These results highlight that different factors known for exerting a mood improving effect differentially regulate neurogenesis along the septo-temporal axis of the hippocampus. Such region and stage specific effects may correlate to distinct functional properties of newborn neurons along the septo-temporal axis of the hippocampus which may contribute differently to the pathophysiology of affective disorders.
-
Members of the transient receptor potential (TRP) cation channel family play important roles in several neuronal functions. To understand the precise role of these channels in information processing, their presence on neuronal elements must be revealed. In this study, we investigated the localization of TRPC6 channels in the adult hippocampal formation. ⋯ Double immunofluorescent staining showed that TRPC6 channels were present in the dendrites of hilar interneurons and hippocampal interneurons with horizontal dendrites in the stratum oriens expressing mGlu1a receptors, whereas parvalbumin immunoreactivity was revealed in TRPC6-expressing dendrites with radial appearance in the stratum radiatum. Electron microscopy showed that the immunogold particles depicting TRPC6 channels were located on the surface membranes of the interneuron dendrites. Our results suggest that TRPC6 channels are in a key position to alter the information entry into the trisynaptic loop of the hippocampal formation from the entorhinal cortex, and to control the function of both feed-forward and feed-back inhibitory circuits in this brain region. © 2012 Wiley Periodicals, Inc.
-
HuD protein is an RNA-binding protein involved in post-transcriptional regulation of gene expression for synaptogenesis, neuronal differentiation, and learning and memory, and is up-regulated and redistributed by a protein kinase C (PKC)-dependent pathway in neurons. Here, we show a PKC-regulated mechanism on HuD-mediated mRNA stability and expression of several neurotrophic factors (NTFs) in cultured hippocampal neurons. HuD pull-down assays showed that HuD is associated with brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin (NT)-3 mRNAs. ⋯ Activated PKC specifically phosphorylated coactivator-associated arginine methyltransferase 1 (CARM1), which methylates HuD and negatively modulates HuD-mRNA interactions during neuronal differentiation, and inhibited its methyltransferase activity, resulting in decrease in CARM1-mediated HuD methylation. Furthermore cotreatment of bryostatin and AMI-1, a specific CARM1 inhibitor, potentiated PKC-dependent HuD-mRNA interactions and enhanced dendritic arborization. These results demonstrate that PKC may play an important role in neuronal differentiation and synaptogenesis via stimulating HuD-mediated mRNA stability and inhibiting CARM1 in hippocampal neurons.
-
Amyloid precursor protein (APP) is an integral membrane glycoprotein present at high levels in nerve cells. Two soluble secreted forms, sAPPα and sAPPβ, are processed from APP by two mutually exclusive proteolytic pathways. sAPPα shows a range of neuroprotective and growth factor properties, including reduction of neuronal injury and improvement in memory performance, in contrast to the generally less potent sAPPβ. In addition, sAPPα has been shown to increase the proliferation of both embryonic neural stem cells and neural progenitor cells (NPCs) derived from the subventricular zone (SVZ) of the adult brain. ⋯ The effect on differential fate was observed in both the presence and absence of depolarizing conditions. Thus, both sAPPα and sAPPβ exert a complex range of effects on SGZ-derived adult NPCs, including increasing NPC proliferation, maintaining cell viability, yet promoting glial over neuronal differentiation. These findings provide the first direct support for the secreted forms of APP regulating SGZ-derived NPCs, and raise the possibility some or all of the effects may have therapeutic benefit in models of neurological disease.