scholarly journals Synaptic Plasticity Shapes Brain Connectivity: Implications for Network Topology

2019 ◽  
Vol 20 (24) ◽  
pp. 6193 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Ennio Iezzi ◽  
Luana Gilio ◽  
Diego Centonze ◽  
Fabio Buttari
Keyword(s):  
Synaptic Plasticity ◽  
Neural Plasticity ◽  
Network Architecture ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Long Term Potentiation ◽  
Brain Network ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Network Organization

Studies of brain network connectivity improved understanding on brain changes and adaptation in response to different pathologies. Synaptic plasticity, the ability of neurons to modify their connections, is involved in brain network remodeling following different types of brain damage (e.g., vascular, neurodegenerative, inflammatory). Although synaptic plasticity mechanisms have been extensively elucidated, how neural plasticity can shape network organization is far from being completely understood. Similarities existing between synaptic plasticity and principles governing brain network organization could be helpful to define brain network properties and reorganization profiles after damage. In this review, we discuss how different forms of synaptic plasticity, including homeostatic and anti-homeostatic mechanisms, could be directly involved in generating specific brain network characteristics. We propose that long-term potentiation could represent the neurophysiological basis for the formation of highly connected nodes (hubs). Conversely, homeostatic plasticity may contribute to stabilize network activity preventing poor and excessive connectivity in the peripheral nodes. In addition, synaptic plasticity dysfunction may drive brain network disruption in neuropsychiatric conditions such as Alzheimer’s disease and schizophrenia. Optimal network architecture, characterized by efficient information processing and resilience, and reorganization after damage strictly depend on the balance between these forms of plasticity.

scholarly journals Childhood trauma history is linked to abnormal brain connectivity in major depression

2019 ◽  
Vol 116 (17) ◽  
pp. 8582-8590 ◽  
Author(s):  
Meichen Yu ◽  
Kristin A. Linn ◽  
Russell T. Shinohara ◽  
Desmond J. Oathes ◽  
Philip A. Cook ◽  
...  
Keyword(s):  
Childhood Trauma ◽  
Network Architecture ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Brain Network ◽  
Childhood Experiences ◽  
Attention Network ◽  
Sensorimotor Network ◽  
Frontoparietal Network ◽  
Subcortical Regions

Patients with major depressive disorder (MDD) present with heterogeneous symptom profiles, while neurobiological mechanisms are still largely unknown. Brain network studies consistently report disruptions of resting-state networks (RSNs) in patients with MDD, including hypoconnectivity in the frontoparietal network (FPN), hyperconnectivity in the default mode network (DMN), and increased connection between the DMN and FPN. Using a large, multisite fMRI dataset (n= 189 patients with MDD,n= 39 controls), we investigated network connectivity differences within and between RSNs in patients with MDD and healthy controls. We found that MDD could be characterized by a network model with the following abnormalities relative to controls: (i) lower within-network connectivity in three task-positive RSNs [FPN, dorsal attention network (DAN), and cingulo-opercular network (CON)], (ii) higher within-network connectivity in two intrinsic networks [DMN and salience network (SAN)], and (iii) higher within-network connectivity in two sensory networks [sensorimotor network (SMN) and visual network (VIS)]. Furthermore, we found significant alterations in connectivity between a number of these networks. Among patients with MDD, a history of childhood trauma and current symptoms quantified by clinical assessments were associated with a multivariate pattern of seven different within- and between-network connectivities involving the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Overall, our study showed that traumatic childhood experiences and dimensional symptoms are linked to abnormal network architecture in MDD. Our results suggest that RSN connectivity may explain underlying neurobiological mechanisms of MDD symptoms and has the potential to serve as an effective diagnostic biomarker.

scholarly journals Modeling Resilience to Damage in Multiple Sclerosis: Plasticity Meets Connectivity

2019 ◽  
Vol 21 (1) ◽  
pp. 143 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Ennio Iezzi ◽  
Luigi Pavone ◽  
Georgia Mandolesi ◽  
Alessandra Musella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Network Architecture ◽  
White Matter Lesions ◽  
Long Term Potentiation ◽  
Chronic Inflammatory Disease ◽  
Brain Network ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Efficient Information

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelinating white matter lesions and neurodegeneration, with a variable clinical course. Brain network architecture provides efficient information processing and resilience to damage. The peculiar organization characterized by a low number of highly connected nodes (hubs) confers high resistance to random damage. Anti-homeostatic synaptic plasticity, in particular long-term potentiation (LTP), represents one of the main physiological mechanisms underlying clinical recovery after brain damage. Different types of synaptic plasticity, including both anti-homeostatic and homeostatic mechanisms (synaptic scaling), contribute to shape brain networks. In MS, altered synaptic functioning induced by inflammatory mediators may represent a further cause of brain network collapse in addition to demyelination and grey matter atrophy. We propose that impaired LTP expression and pathologically enhanced upscaling may contribute to disrupting brain network topology in MS, weakening resilience to damage and negatively influencing the disease course.

scholarly journals Identifying Diurnal Variability of Brain Connectivity Patterns Using Graph Theory

2021 ◽  
Vol 11 (1) ◽  
pp. 111
Author(s):  
Farzad V. Farahani ◽  
Magdalena Fafrowicz ◽  
Waldemar Karwowski ◽  
Bartosz Bohaterewicz ◽  
Anna Maria Sobczak ◽  
...  
Keyword(s):  
Resting State ◽  
Network Architecture ◽  
Inferior Frontal Gyrus ◽  
Brain Network ◽  
Time Of Day ◽  
Precentral Gyrus ◽  
Network Organization ◽  
Diurnal Variability ◽  
Sleep Inertia ◽  
Brain Functions

Significant differences exist in human brain functions affected by time of day and by people’s diurnal preferences (chronotypes) that are rarely considered in brain studies. In the current study, using network neuroscience and resting-state functional MRI (rs-fMRI) data, we examined the effect of both time of day and the individual’s chronotype on whole-brain network organization. In this regard, 62 participants (39 women; mean age: 23.97 ± 3.26 years; half morning- versus half evening-type) were scanned about 1 and 10 h after wake-up time for morning and evening sessions, respectively. We found evidence for a time-of-day effect on connectivity profiles but not for the effect of chronotype. Compared with the morning session, we found relatively higher small-worldness (an index that represents more efficient network organization) in the evening session, which suggests the dominance of sleep inertia over the circadian and homeostatic processes in the first hours after waking. Furthermore, local graph measures were changed, predominantly across the left hemisphere, in areas such as the precentral gyrus, putamen, inferior frontal gyrus (orbital part), inferior temporal gyrus, as well as the bilateral cerebellum. These findings show the variability of the functional neural network architecture during the day and improve our understanding of the role of time of day in resting-state functional networks.

scholarly journals Emerging Link between Alzheimer’s Disease and Homeostatic Synaptic Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Sung-Soo Jang ◽  
Hee Jung Chung
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Senile Plaques ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Homeostatic Plasticity ◽  
Brain Disorder

Alzheimer’s disease (AD) is an irreversible brain disorder characterized by progressive cognitive decline and neurodegeneration of brain regions that are crucial for learning and memory. Although intracellular neurofibrillary tangles and extracellular senile plaques, composed of insoluble amyloid-β(Aβ) peptides, have been the hallmarks of postmortem AD brains, memory impairment in early AD correlates better with pathological accumulation of soluble Aβoligomers and persistent weakening of excitatory synaptic strength, which is demonstrated by inhibition of long-term potentiation, enhancement of long-term depression, and loss of synapses. However, current, approved interventions aiming to reduce Aβlevels have failed to retard disease progression; this has led to a pressing need to identify and target alternative pathogenic mechanisms of AD. Recently, it has been suggested that the disruption of Hebbian synaptic plasticity in AD is due to aberrant metaplasticity, which is a form of homeostatic plasticity that tunes the magnitude and direction of future synaptic plasticity based on previous neuronal or synaptic activity. This review examines emerging evidence for aberrant metaplasticity in AD. Putative mechanisms underlying aberrant metaplasticity in AD will also be discussed. We hope this review inspires future studies to test the extent to which these mechanisms contribute to the etiology of AD and offer therapeutic targets.

scholarly journals Modulation of network activity and induction of homeostatic synaptic plasticity by enzymatic removal of heparan sulfates

2014 ◽  
Vol 369 (1654) ◽  
pp. 20140134 ◽  
Author(s):  
Svetlana Korotchenko ◽  
Lorenzo A. Cingolani ◽  
Tatiana Kuznetsova ◽  
Luca Leonardo Bologna ◽  
Michela Chiappalone ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strong Increase ◽  
Bioelectrical Activity ◽  
Highly Active ◽  
Homeostatic Synaptic Plasticity ◽  
Term Potentiation ◽  
Heparan Sulfates

Heparan sulfates (HSs) are complex and highly active molecules that are required for synaptogenesis and long-term potentiation. A deficit in HSs leads to autistic phenotype in mice. Here, we investigated the long-term effect of heparinase I, which digests highly sulfated HSs, on the spontaneous bioelectrical activity of neuronal networks in developing primary hippocampal cultures. We found that chronic heparinase treatment led to a significant reduction of the mean firing rate of neurons, particularly during the period of maximal neuronal activity. Furthermore, firing pattern in heparinase-treated cultures often appeared as epileptiform bursts, with long periods of inactivity between them. These changes in network activity were accompanied by an increase in the frequency and amplitude of miniature postsynaptic excitatory currents, which could be described by a linear up-scaling of current amplitudes. Biochemically, we observed an upregulation in the expression of the glutamate receptor subunit GluA1, but not GluA2, and a strong increase in autophosphorylation of α and β Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), without changes in the levels of kinase expression. These data suggest that a deficit in HSs triggers homeostatic synaptic plasticity and drastically affects functional maturation of neural network.

scholarly journals Brain Network Organization Correlates with Autistic Features in Preschoolers with Autism Spectrum Disorders and in Their Fathers: Preliminary Data from a DWI Analysis

2019 ◽  
Vol 8 (4) ◽  
pp. 487 ◽  
Author(s):  
Billeci ◽  
Calderoni ◽  
Conti ◽  
Lagomarsini ◽  
Narzisi ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Brain Connectivity ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Brain Network ◽  
Local Network ◽  
Network Organization ◽  
Frontal Pole ◽  
Structural Network ◽  
Spectrum Disorders

Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders that is characterized by an altered brain connectivity organization. Autistic traits below the clinical threshold (i.e., the broad autism phenotype; BAP) are frequent among first-degree relatives of subjects with ASD; however, little is known regarding whether subthreshold behavioral manifestations of ASD mirror also at the neuroanatomical level in parents of ASD probands. To this aim, we applied advanced diffusion network analysis to MRI of 16 dyads consisting of a child with ASD and his father in order to investigate: (i) the correlation between structural network organization and autistic features in preschoolers with ASD (all males; age range 1.5–5.2 years); (ii) the correlation between structural network organization and BAP features in the fathers of individuals with ASD (fath-ASD). Local network measures significantly correlated with autism severity in ASD children and with BAP traits in fath-ASD, while no significant association emerged when considering the global measures of brain connectivity. Notably, an overlap of some brain regions that are crucial for social functioning (cingulum, superior temporal gyrus, inferior temporal gyrus, middle frontal gyrus, frontal pole, and amygdala) in patients with ASD and fath-ASD was detected, suggesting an intergenerational transmission of these neural substrates. Overall, the results of this study may help in elucidating the neurostructural endophenotype of ASD, paving the way for bridging connections between underlying genetic and ASD symptomatology.

scholarly journals Functional Connectivity Network Disruption Underlies Domain-Specific Impairments in Attention for Children Born Very Preterm

2020 ◽  
Author(s):  
M D Wheelock ◽  
R E Lean ◽  
S Bora ◽  
T R Melzer ◽  
A T Eggebrecht ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Network Architecture ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Attention Problems ◽  
School Age Children ◽  
Prospective Longitudinal Study ◽  
Domain Specific ◽  
Very Preterm ◽  
Prospective Longitudinal

Abstract Attention problems are common in school-age children born very preterm (VPT; < 32 weeks gestational age), but the contribution of aberrant functional brain connectivity to these problems is not known. As part of a prospective longitudinal study, brain functional connectivity (fc) was assessed alongside behavioral measures of selective, sustained, and executive attention in 58 VPT and 65 full-term (FT) born children at corrected-age 12 years. VPT children had poorer sustained, shifting, and divided attention than FT children. Within the VPT group, poorer attention scores were associated with between-network connectivity in ventral attention, visual, and subcortical networks, whereas between-network connectivity in the frontoparietal, cingulo-opercular, dorsal attention, salience and motor networks was associated with attention functioning in FT children. Network-level differences were also evident between VPT and FT children in specific attention domains. Findings contribute to our understanding of fc networks that potentially underlie typical attention development and suggest an alternative network architecture may help support attention in VPT children.

scholarly journals GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus

2016 ◽  
Vol 115 (6) ◽  
pp. 2989-2996 ◽  
Author(s):  
J. Huupponen ◽  
T. Atanasova ◽  
T. Taira ◽  
S. E. Lauri
Keyword(s):  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Activity Patterns ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Postnatal Period ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Hippocampal Pyramidal Neurons ◽  
Activity Dependent

Development of the neuronal circuitry involves both Hebbian and homeostatic plasticity mechanisms that orchestrate activity-dependent refinement of the synaptic connectivity. AMPA receptor subunit GluA4 is expressed in hippocampal pyramidal neurons during early postnatal period and is critical for neonatal long-term potentiation; however, its role in homeostatic plasticity is unknown. Here we show that GluA4-dependent plasticity mechanisms allow immature synapses to promptly respond to alterations in network activity. In the neonatal CA3, the threshold for homeostatic plasticity is low, and a 15-h activity blockage with tetrodotoxin triggers homeostatic upregulation of glutamatergic transmission. On the other hand, attenuation of the correlated high-frequency bursting in the CA3-CA1 circuitry leads to weakening of AMPA transmission in CA1, thus reflecting a critical role for Hebbian synapse induction in the developing CA3-CA1. Both of these developmentally restricted forms of plasticity were absent in GluA4 −/− mice. These data suggest that GluA4 enables efficient homeostatic upscaling and responsiveness to temporal activity patterns during the critical period of activity-dependent refinement of the circuitry.

scholarly journals Identification of neural oscillations and epileptiform changes in human brain organoids

2019 ◽  
Author(s):  
Ranmal A. Samarasinghe ◽  
Osvaldo A. Miranda ◽  
Simon Mitchell ◽  
Isabella Ferando ◽  
Momoko Watanabe ◽  
...  
Keyword(s):  
Neural Network ◽  
Human Brain ◽  
Network Architecture ◽  
Network Formation ◽  
Neurological Diseases ◽  
Extracellular Recording ◽  
Brain Network ◽  
Network Activity ◽  
Intact Brain ◽  
Oscillatory Network

ABSTRACTHuman brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.

scholarly journals Chronic neuronal excitation leads to homeostatic suppression of structural long-term potentiation

2021 ◽  
Author(s):  
Hiromi H Ueda ◽  
Aiko Sato ◽  
Maki Onda ◽  
Hideji Murakoshi
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Ca1 Neurons ◽  
Downstream Signaling ◽  
Neuronal Excitation ◽  
Term Potentiation ◽  
Hippocampal Ca1

Synaptic plasticity is long-lasting changes in synaptic currents and structure. When neurons are exposed to signals that induce aberrant neuronal excitation, they increase the threshold for the induction of synaptic plasticity, called homeostatic plasticity. To further understand the homeostatic regulation of synaptic plasticity and its molecular mechanisms, we investigated glutamate uncaging/photoactivatable (pa)CaMKII-dependent sLTP induction in hippocampal CA1 neurons after chronic neuronal excitation by GABAA receptor antagonists. The neuronal excitation suppressed the glutamate uncaging-evoked Ca2+ influx and failed to induce sLTP. Single-spine optogenetic stimulation using paCaMKII also failed to induce sLTP, suggesting that CaMKII downstream signaling is impaired in response to chronic neuronal excitation. Furthermore, while the inhibition of Ca2+ influx was protein synthesis-independent, paCaMKII-induced sLTP depended on it. Our findings demonstrate that chronic neuronal excitation suppresses sLTP in two independent ways (i.e., the inhibitions of Ca2+ influx and CaMKII downstream signaling), which may contribute to the robust neuronal protection in excitable environments.

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