scholarly journals Trans-Synaptic Spread of Amyloid-βin Alzheimer’s Disease: Paths toβ-Amyloidosis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Annabella Pignataro ◽  
Silvia Middei
Keyword(s):  
Neuronal Activity ◽  
Amyloid Plaques ◽  
Brain Regions ◽  
Amyloid Peptide ◽  
Synaptic Connections ◽  
Brain Areas ◽  
Close Link ◽  
Gradual Accumulation ◽  
Cortical Regions ◽  
Activity Dependent

Neuronal activity has a strong causal role in the production and release of the neurotoxicβ-amyloid peptide (Aβ). Because of this close link, gradual accumulation of Aβinto amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elevated activation at resting state. However, the link between Aβand activity is not always linear and recent studies report exceptions to the view of “more activity, more plaques.” Here, we review the literature about the activity-dependent production of Aβin both human cases and AD models and focus on the evidences that brain regions with elevated convergence of synaptic connections (herein referred to as brain nodes) are particularly vulnerable to Aβaccumulation. Next, we will examine data supporting the hypothesis that, since Aβis released from synaptic terminals,β-amyloidosis can spread in AD brain by advancing through synaptically connected regions, which makes brain nodes vulnerable to Aβaccumulation. Finally, we consider possible mechanisms that account forβ-amyloidosis progression through synaptically linked regions.

scholarly journals Systematic identification of 3′-UTR regulatory elements in activity-dependent mRNA stability in hippocampal neurons

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130509 ◽  
Author(s):  
Jonathan E. Cohen ◽  
Philip R. Lee ◽  
R. Douglas Fields
Keyword(s):  
Neuronal Activity ◽  
Mrna Stability ◽  
Hippocampal Neurons ◽  
Transcriptional Control ◽  
Regulatory Elements ◽  
Memory Storage ◽  
Long Term Memory ◽  
Synaptic Connections ◽  
Activity Dependent

Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long-term memory storage. Activity-dependent, post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity in rat hippocampal neurons. In this study, we demonstrate rapid, post-transcriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3′-UTRs of destabilized transcripts, identifies enrichment in sequence motifs corresponding to microRNA (miRNA)-binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further find that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.

scholarly journals microRNA profiling uncovers region-specific molecular correlates of threat responses in a marmoset model of anxiety

2021 ◽  
Author(s):  
Natalia Popa ◽  
Angela C Roberts ◽  
Andrea M Santangelo ◽  
Eduardo Gascon
Keyword(s):  
Emotional Regulation ◽  
Brain Regions ◽  
Molecular Heterogeneity ◽  
Depression And Anxiety ◽  
Behavioral Differences ◽  
Brain Areas ◽  
Molecular Changes ◽  
Highly Correlated ◽  
Cortical Regions ◽  
And Behavior

Background: Neuroimaging studies have consistently reported that stress-related disorders such as depression and anxiety impinge on the activity of emotion regulation networks, namely in the ventromedial prefrontal cortex (vmPFC). This circuitry is known to be extensively modulated by serotonin and it has been long shown that genetic polymorphisms in the serotonin transporter gene (SLC6A4) are linked to anxiey and depression. vmPFC encompasses different brain regions in terms of cytoarchitecture, activity and connectivity. However, molecular heterogeneity within the vmPFC and how these differences affect emotional regulation and behavior have not been elucidated. Methods: Here, we took advantage of recently described polymorphisms in marmoset SLC6A4 gene linked to alter threat responses. Using FACS-sorted cells from different brain areas of genotyped marmosets, we tested the hypothesis that specific molecular changes in precise regions of the vmPFC underlie the behavioral differences and can be associated with high anxiety-like trait. Results: miRNA analysis of FACS-sorted cells from marmoset cortex revealed that clear miRNA profiles can be identified for different cell subsets (NeuN+ versus NeuN- cells) or cortical regions (visual cortex versus vmPFC). More importantly, marmosets bearing different SLC6A4 polymorphisms show distinct miRNAs signatures specifically in vmPFC area 32 neurons but not in the closely related vmPFC area 25 neurons. Finally, levels of these miRNAs were highly correlated to the anxiety-like score in a test of uncertain threat. Conclusions: These data demonstrate that molecular changes within area 32 likely underlie the differential anxiety-like responses associated with SLC6A4 polymorphisms.

scholarly journals Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke

2019 ◽  
Vol 116 (27) ◽  
pp. 13621-13630 ◽  
Author(s):  
Huixuan Liang ◽  
Handi Zhao ◽  
Amy Gleichman ◽  
Michal Machnicki ◽  
Sagar Telang ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Spontaneous Recovery ◽  
Brain Regions ◽  
Lineage Tracing ◽  
Synaptic Connections ◽  
Cellular Activity ◽  
Functional Effect ◽  
Tetanus Neurotoxin ◽  
Activity Dependent ◽  
Increased Activity

Stroke is the leading cause of adult disability. Neurogenesis after stroke is associated with repair; however, the mechanisms regulating poststroke neurogenesis and its functional effect remain unclear. Here, we investigate multiple mechanistic routes of induced neurogenesis in the poststroke brain, using both a forelimb overuse manipulation that models a clinical neurorehabilitation paradigm, as well as local manipulation of cellular activity in the peri-infarct cortex. Increased activity in the forelimb peri-infarct cortex via either modulation drives increased subventricular zone (SVZ) progenitor proliferation, migration, and neuronal maturation in peri-infarct cortex. This effect is sensitive to competition from neighboring brain regions. By using orthogonal tract tracing and rabies virus approaches in transgenic SVZ-lineage-tracing mice, SVZ-derived neurons synaptically integrate into the peri-infarct cortex; these effects are enhanced with forelimb overuse. Synaptic transmission from these newborn SVZ-derived neurons is critical for spontaneous recovery after stroke, as tetanus neurotoxin silencing specifically of the SVZ-derived neurons disrupts the formation of these synaptic connections and hinders functional recovery after stroke. SVZ-derived neurogenesis after stroke is activity-dependent, region-specific, and sensitive to modulation, and the synaptic connections formed by these newborn cells are functionally critical for poststroke recovery.

scholarly journals Optimal synaptic dynamics for memory maintenance in the presence of noise

2020 ◽  
Author(s):  
Dhruva V Raman ◽  
Timothy O’Leary
Keyword(s):  
Neural Circuit ◽  
Behavioural Change ◽  
Experimental Measurements ◽  
Synaptic Connections ◽  
Biological Noise ◽  
Brain Areas ◽  
Dependent Component ◽  
Synaptic Dynamics ◽  
Circuit Function ◽  
Activity Dependent

ABSTRACTSynaptic connections in many brain areas have been found to fluctuate significantly, with substantial turnover and remodelling occurring over hours to days. Remarkably, this flux in connectivity persists in the absence of overt learning or behavioural change. What proportion of these ongoing fluctuations can be attributed to systematic plasticity processes that maintain memories and neural circuit function? We show under general conditions that the optimal magnitude of systematic plasticity is typically less than the magnitude of perturbations due to internal biological noise. Thus, for any given amount of unavoidable noise, 50% or more of total synaptic turnover should be effectively random for optimal memory maintenance. Our analysis does not depend on specific neural circuit architectures or plasticity mechanisms and predicts previously unexplained experimental measurements of the activity-dependent component of ongoing plasticity.

Cortical Regions Associated with Perceiving, Naming, and Knowing about Colors

1999 ◽  
Vol 11 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Linda L. Chao ◽  
Alex Martin
Keyword(s):  
Color Perception ◽  
Brain Regions ◽  
Gray Scale ◽  
Brain Areas ◽  
Low Level ◽  
Positron Emission ◽  
Specific Object ◽  
Cortical Regions ◽  
Object Form ◽  
Parietal Cortices

Positron emission tomography (PET) was used to investigate whether retrieving information about a specific object attribute requires reactivation of brain areas that mediate perception of that attribute. During separate PET scans, subjects passively viewed colored and equiluminant gray-scale Mondrians, named colored and achromatic objects, named the color of colored objects, and generated color names associated with achromatic objects. Color perception was associated with activations in the lingual and fusiform gyri of the occipital lobes, consistent with previous neuroimaging and human lesion studies. Retrieving information about object color (generating color names for achromatic objects relative to naming achromatic objects) activated the left inferior temporal, left frontal, and left posterior parietal cortices, replicating previous findings from this laboratory. When subjects generated color names for achromatic objects relative to the low-level baseline of viewing gray-scale Mondrians, additional activations in the left fusi-form/lateral occipital region were detected. However, these activations were lateral to the occipital regions associated with color perception and identical to occipital regions activated when subjects simply named achromatic objects relative to the same low-level baseline. This suggests that the occipital activa-tions associated with retrieving color information were due to the perception of object form rather than to the top-down influence of brain areas that mediate color perception. Taken together, these results indicate that retrieving previously acquired information about an object's typical color does not require reactivation of brain regions that subserve color perception.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

Engaging regularly with fiction influences connectivity in cortical areas for language and mentalizing

2017 ◽  
Author(s):  
Roel M. Willems ◽  
Franziska Hartung
Keyword(s):  
Functional Connectivity ◽  
Time Course ◽  
Language Skills ◽  
Brain Regions ◽  
Brain Areas ◽  
Daily Lives ◽  
Cortical Areas ◽  
Social Abilities ◽  
Behavioral Evidence ◽  
Amount Of Reading

Behavioral evidence suggests that engaging with fiction is positively correlated with social abilities. The rationale behind this link is that engaging with fictional narratives offers a ‘training modus’ for mentalizing and empathizing. We investigated the influence of the amount of reading that participants report doing in their daily lives, on connections between brain areas while they listened to literary narratives. Participants (N=57) listened to two literary narratives while brain activation was measured with fMRI. We computed time-course correlations between brain regions, and compared the correlation values from listening to narratives to listening to reversed speech. The between-region correlations were then related to the amount of fiction that participants read in their daily lives. Our results show that amount of fiction reading is related to functional connectivity in areas known to be involved in language and mentalizing. This suggests that reading fiction influences social cognition as well as language skills.

scholarly journals The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Kynurenic Acid ◽  
Neuronal Damage ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Hippocampal Field ◽  
Power Spectral ◽  
Density Values ◽  
Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

scholarly journals Cochlear activity in silent cue-target intervals shows a theta-rhythmic pattern and is correlated to attentional alpha and theta modulations

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Moritz Herbert Albrecht Köhler ◽  
Gianpaolo Demarchi ◽  
Nathan Weisz
Keyword(s):  
Selective Attention ◽  
Brain Regions ◽  
Attentional Focus ◽  
Theta Activity ◽  
Superior Olivary Complex ◽  
Rhythmic Pattern ◽  
Auditory Input ◽  
Auditory Selective Attention ◽  
Beta Power ◽  
Cortical Regions

AbstractBackgroundA long-standing debate concerns where in the processing hierarchy of the central nervous system (CNS) selective attention takes effect. In the auditory system, cochlear processes can be influenced via direct and mediated (by the inferior colliculus) projections from the auditory cortex to the superior olivary complex (SOC). Studies illustrating attentional modulations of cochlear responses have so far been limited to sound-evoked responses. The aim of the present study is to investigate intermodal (audiovisual) selective attention in humans simultaneously at the cortical and cochlear level during a stimulus-free cue-target interval.ResultsWe found that cochlear activity in the silent cue-target intervals was modulated by a theta-rhythmic pattern (~ 6 Hz). While this pattern was present independently of attentional focus, cochlear theta activity was clearly enhanced when attending to the upcoming auditory input. On a cortical level, classical posterior alpha and beta power enhancements were found during auditory selective attention. Interestingly, participants with a stronger release of inhibition in auditory brain regions show a stronger attentional modulation of cochlear theta activity.ConclusionsThese results hint at a putative theta-rhythmic sampling of auditory input at the cochlear level. Furthermore, our results point to an interindividual variable engagement of efferent pathways in an attentional context that are linked to processes within and beyond processes in auditory cortical regions.

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