Mechanisms of Synapse and Dendrite Maintenance and Their Disruption in Psychiatric and Neurodegenerative Disorders

Lin, Yu‐Chih; Koleske, Anthony J.

doi:10.1146/annurev-neuro-060909-153204

Cited by 225 publications

(217 citation statements)

References 230 publications

(305 reference statements)

Supporting

Mentioning

212

Contrasting

Order By: Relevance

“…This poor dendritic growth and branching and/or dendritic atrophy secondary to a loss of functional synapses on destroyed dendritic spines (Diamond et al, 2006;Chen et al, 2008;Lin and Koleske, 2010) may progress with age (Brunson et al, 2005;Ivy et al, 2010). Support for this possibility emerges from studies using transgenic mice (Wang et al, , 2012.…”

Section: Cognitive Consequences Of Early-life Experience Via Disruptimentioning

confidence: 99%

“…Thus, poor dendritic growth and branching may be a result of abnormal levels of glucocorticoids and their actions on cognate receptors (GR) (Alfarez et al, 2009;Liston and Gan, 2011). Alternatively, dendrites may atrophy, secondary to a loss of functional synapses on the destroyed dendritic spines (Lin and Koleske, 2010). In support of this idea, dendritic spines and novel mechanisms for these changes are emerging, including glucocorticoid receptor-mediated induction of actin-binding proteins (Liston and Gan, 2011).…”

Section: The Toolbox Of Early-life Stressmentioning

confidence: 99%

See 1 more Smart Citation

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

Chen

Baram

2015

Neuropsychopharmacol

404

327

View full text Add to dashboard Cite

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational methodologies. Because early-life adversity is a powerful determinant of subsequent vulnerabilities to emotional and cognitive pathologies, understanding the underlying processes will have profound implications for the world's current and future children.

show abstract

Section: Cognitive Consequences Of Early-life Experience Via Disruptimentioning

confidence: 99%

Section: The Toolbox Of Early-life Stressmentioning

confidence: 99%

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

Chen

Baram

2015

Neuropsychopharmacol

404

327

View full text Add to dashboard Cite

show abstract

“…In addition, they contribute to plasticity of synaptic transmission, mainly by binding to specific effector proteins, which induce posttranslational modifications regulating the trafficking and function of neurotransmitter receptors and other signaling molecules. Given the central role of PSD scaffolding molecules, even minor alterations in their expression, trafficking, regulation, or function have been associated with brain disease [7,[10][11][12]. Therefore, identifying and correcting these dysfunctions might provide promising new avenues for drug therapy.…”

Section: Introductionmentioning

confidence: 99%

Molecular and functional heterogeneity of GABAergic synapses

Fritschy

Panzanelli

Tyagarajan

2012

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Knowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA(A) receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABA(A) receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA(A) receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses. AbstractKnowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA A receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABA A receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA A receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophinglycoprotein complex to the molecular ...

show abstract

“…First, neuronal nuclei are extracted based on a neuronal marker (color =…) (3,4). In parallel, a Laplace filter enhances (5) the detection (6) of nuclear folds and edges of the nuclei on lamin-stained images.…”

Section: Figure 3 -Quantification Of Nuclear Foldingmentioning

confidence: 99%

“…the production of toxic protein oligomers, cytoskeletal dysregulation, etc. ), disrupted neuronal plasticity represents a pathological hallmark that is shared by numerous psychiatric and neurodegenerative diseases, including schizophrenia, autism spectrum disorder and Alzheimer's disease 3,4 . Thus, understanding the intricacies of neuronal connectivity may not only be instrumental in gaining insights into its physiological importance, but also in resolving stages of disease development.…”

Section: Introductionmentioning

confidence: 99%

Image Informatics Strategies for Deciphering Neuronal Network Connectivity

Detrez

Verstraelen

Gebuis

et al. 2016

Focus on Bio-Image Informatics

View full text Add to dashboard Cite

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphological plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular communication and the associated calcium-bursting behaviour. In vitro cultured neuronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies.2

show abstract

Mechanisms of Synapse and Dendrite Maintenance and Their Disruption in Psychiatric and Neurodegenerative Disorders

Cited by 225 publications

References 230 publications

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

Molecular and functional heterogeneity of GABAergic synapses

Image Informatics Strategies for Deciphering Neuronal Network Connectivity

Contact Info

Product

Resources

About