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An ethyl acetate fraction from Aralia elata (AEEF) was investigated to confirm its neuronal cell protective effect on ethanol-induced cytotoxicity in MC-IXC cells and its ameliorating effect on neurodegeneration in chronic alcohol-induced mice. The neuroprotective effect was examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) assays. As a result, AEEF reduced alcohol-induced cytotoxicity and oxidative stress. To evaluate the improvement of learning, memory ability, and spatial cognition, Y-maze, passive avoidance, and Morris water maze tests were conducted. The AEEF groups showed an alleviation of the decrease in cognitive function in alcohol-treated mice. Then, malondialdehyde (MDA) levels and the superoxide dismutase (SOD) content were measured to evaluate the antioxidant effect of AEEF in the brain tissue. Treatment with AEEF showed a considerable ameliorating effect on biomarkers such as SOD and MDA content in alcohol-induced mice. To assess the cerebral cholinergic system involved in neuronal signaling, acetylcholinesterase (AChE) activity and acetylcholine (ACh) content were measured. The AEEF groups showed increased ACh levels and decreased AChE activities. In addition, AEEF prevented alcohol-induced neuronal apoptosis via improvement of mitochondrial activity, including reactive oxygen species levels, mitochondrial membrane potential, and adenosine triphosphate content. AEEF inhibited apoptotic signals by regulating phosphorylated c-Jun N-terminal kinases ( p -JNK), phosphorylated protein kinase B ( p -Akt), Bcl-2-associated X protein (BAX), and phosphorylated Tau ( p -Tau). Finally, the bioactive compounds of AEEF were identified as caffeoylquinic acid (CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and chikusetsusaponin IVa using the UPLC-Q-TOF-MS system.

Recording the activity of large populations of neurons is an important step toward understanding the emergent function of neural circuits. Here we present a simple holographic method to simultaneously perform two-photon calcium imaging of neuronal populations across multiple areas and layers of mouse cortex in vivo. We use prior knowledge of neuronal locations, activity sparsity, and a constrained nonnegative matrix factorization algorithm to extract signals from neurons imaged simultaneously and located in different focal planes or fields of view. Our laser multiplexing approach is simple and fast, and could be used as a general method to image the activity of neural circuits in three dimensions across multiple areas in the brain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although the functional properties of individual neurons in primary visual cortex have been studied intensely, little is known about how neuronal groups could encode changing visual stimuli using temporal activity patterns. To explore this, we used in vivo two-photon calcium imaging to record the activity of neuronal populations in primary visual cortex of awake mice in the presence and absence of visual stimulation. Multidimensional analysis of the network activity allowed us to identify neuronal ensembles defined as groups of cells firing in synchrony. These synchronous groups of neurons were themselves activated in sequential temporal patterns, which repeated at much higher proportions than chance and were triggered by specific visual stimuli such as natural visual scenes. Interestingly, sequential patterns were also present in recordings of spontaneous activity without any sensory stimulation and were accompanied by precise firing sequences at the single-cell level. Moreover, intrinsic dynamics could be used to predict the occurrence of future neuronal ensembles. Our data demonstrate that visual stimuli recruit similar sequential patterns to the ones observed spontaneously, consistent with the hypothesis that already existing Hebbian cell assemblies firing in predefined temporal sequences could be the microcircuit substrate that encodes visual percepts changing in time., (Copyright © 2015 Carrillo-Reid et al.)

The cortical microcircuit is built with recurrent excitatory connections, and it has long been suggested that the purpose of this design is to enable intrinsically driven reverberating activity. To understand the dynamics of neocortical intrinsic activity better, we performed two-photon calcium imaging of populations of neurons from the primary visual cortex of awake mice during visual stimulation and spontaneous activity. In both conditions, cortical activity is dominated by coactive groups of neurons, forming ensembles whose activation cannot be explained by the independent firing properties of their contributing neurons, considered in isolation. Moreover, individual neurons flexibly join multiple ensembles, vastly expanding the encoding potential of the circuit. Intriguingly, the same coactive ensembles can repeat spontaneously and in response to visual stimuli, indicating that stimulus-evoked responses arise from activating these intrinsic building blocks. Although the spatial properties of stimulus-driven and spontaneous ensembles are similar, spontaneous ensembles are active at random intervals, whereas visually evoked ensembles are time-locked to stimuli. We conclude that neuronal ensembles, built by the coactivation of flexible groups of neurons, are emergent functional units of cortical activity and propose that visual stimuli recruit intrinsically generated ensembles to represent visual attributes.

Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is critical in the pathogenesis of Alzheimer's disease. Abeta is produced by neurons and released into the brain interstitial fluid (ISF), a process regulated by synaptic activity. To determine whether behavioral stressors can regulate ISF Abeta levels, we assessed the effects of chronic and acute stress paradigms in amyloid precursor protein transgenic mice. Isolation stress over 3 months increased Abeta levels by 84%. Similarly, acute restraint stress increased Abeta levels over hours. Exogenous corticotropin-releasing factor (CRF) but not corticosterone mimicked the effects of acute restraint stress. Inhibition of endogenous CRF receptors or neuronal activity blocked the effects of acute stress on Abeta. Thus, behavioral stressors can rapidly increase ISF Abeta through neuronal activity in a CRF-dependent manner, and the results suggest a mechanism by which behavioral stress may affect Alzheimer's disease pathogenesis.

Dual specific protein kinase Dyrks are thought to play a key role in the regulation of cell growth in a variety of cellular systems. Interestingly, human Dyrk1 is mapped to the Down's syndrome (DS) critical region on chromosome 21, and thought to be a candidate gene responsible for the mental retardation of DS patients. Huntingtin-interacting protein 1 (Hip-1), a proapoptotic mediator, is implicated as a molecular accomplice in the pathogenesis of Huntington's disease. In the present study we found that Dyrk1 selectively binds to and phosphorylates Hip-1 during the neuronal differentiation of embryonic hippocampal neuroprogenitor (H19-7) cells. The Dyrk1-mediated phosphorylation of Hip-1, in response to bFGF, resulted in the blockade of Hip-1-mediated neuronal cell death as well as the enhancement of neurite outgrowth. Furthermore, the addition of etoposide to proliferating H19-7 cells caused the diminished binding of Hip-1 to Dyrk1 and the levels of phosphorylated Hip-1 remarkably decreased. Simultaneously, the dissociated Hip-1 from Dyrk1 bound to caspase-3 in response to etoposide, which led to its activation and consequently cell death in H19-7 cells. These data suggest that the phosphorylation of Hip-1 by Dyrk1 has a dual role in regulating neuronal differentiation and cell death. The interaction between Dyrk1 and Hip-1 appeared to be differentially modulated by different kinds of stimuli, such as bFGF and etoposide in H19-7 cells., (Copyright 2005 Wiley-Liss, Inc.)