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Cells Jul 2021Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family...
Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family with sequence similarity 19 A1 (FAM19A1) is a secreted protein primarily expressed in subsets of terminally differentiated neuronal precursor cells and fully mature neurons in specific brain substructures. Several recent studies have demonstrated the importance of FAM19A1 in brain physiology; however, additional information is needed to support its role in neuronal maturation and function. In this study, dendritic spine morphology in -ablated mice and neurite development during in vitro neurogenesis were examined to understand the putative role of FAM19A1 in neural integrity. Adult -deficient mice showed low dendritic spine density and maturity with reduced dendrite complexity compared to wild-type (WT) littermates. To further explore the effect of FAM19A1 on neuronal maturation, the neurite outgrowth pattern in primary neurons was analyzed in vitro with and without FAM19A1. In response to FAM19A1, WT primary neurons showed reduced neurite complexity, whereas -decifient primary neurons exhibited increased neurite arborization, which was reversed by supplementation with recombinant FAM19A1. Together, these findings suggest that FAM19A1 participates in dendritic spine development and neurite arborization.
Topics: Age Factors; Animals; Brain; Cells, Cultured; Chemokines; Dendritic Spines; Female; Gestational Age; Male; Mice, Inbred C57BL; Mice, Knockout; Neurites; Neuronal Outgrowth; Pregnancy; Signal Transduction; Mice
PubMed: 34440636
DOI: 10.3390/cells10081868 -
Neurobiology of Learning and Memory Feb 2017The introduction of novel technologies, including high resolution time lapse imaging in behaving animals, molecular modification of the genome and optogenetic control of... (Review)
Review
The introduction of novel technologies, including high resolution time lapse imaging in behaving animals, molecular modification of the genome and optogenetic control of neuronal excitability have revolutionized the ability to detect subcellular changes in the brain, associated with learning and memory. The sequence of molecular cascades leading to formation, longevity and erasure of memories are being addressed in growing number of studies. Still, major issues concerning the relationship between the morphology and physiology of dendritic spines and memory mechanisms and the functional, neuronal network relevance of such parameters remain unsettled. The present review will summarize recent studies related to the immediate and long lasting changes in density, morphology and function of dendritic spines and their parent neurons following exposure to plasticity-producing stimulation in vivo and in vitro. Standing issues such as the relations between volume/shape and longevity, with respect to different classes of memories in different brain regions will be addressed. These studies indicate that the rules governing the structure/function relations of dendritic spines and memory in the brain are still not conclusive.
Topics: Animals; Dendritic Spines; Hippocampus; Humans; Long-Term Potentiation; Memory; Neurons; Synapses
PubMed: 27311757
DOI: 10.1016/j.nlm.2016.06.007 -
Biomolecules Nov 2021Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined... (Review)
Review
Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined areas. These membrane lateral heterogeneities range from nanoscopic dimensions, often involving only a few molecular constituents, to micron-sized mesoscopic domains resulting from the coalescence of nanodomains. Short-lived domains lasting for a few milliseconds coexist with more stable platforms lasting from minutes to days. This panoply of lateral domains subserves the great variety of demands of cell physiology, particularly high for those implicated in signaling. The dendritic spine, a subcellular structure of neurons at the receiving (postsynaptic) end of central nervous system excitatory synapses, exploits this compartmentalization principle. In its most frequent adult morphology, the mushroom-shaped spine harbors neurotransmitter receptors, enzymes, and scaffolding proteins tightly packed in a volume of a few femtoliters. In addition to constituting a mesoscopic lateral heterogeneity of the dendritic arborization, the dendritic spine postsynaptic membrane is further compartmentalized into spatially delimited nanodomains that execute separate functions in the synapse. This review discusses the functional relevance of compartmentalization and nanodomain organization in synaptic transmission and plasticity and exemplifies the importance of this parcelization in various neurotransmitter signaling systems operating at dendritic spines, using two fast ligand-gated ionotropic receptors, the nicotinic acetylcholine receptor and the glutamatergic receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as paradigmatic examples.
Topics: Dendritic Spines; Neurons; Synapses; Synaptic Transmission
PubMed: 34827695
DOI: 10.3390/biom11111697 -
Cells Feb 2020The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory...
The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.
Topics: Animals; Dendritic Spines; Doublecortin Protein; Humans; MAP Kinase Kinase 4; MAP Kinase Signaling System; Mice; Morris Water Maze Test; Transfection
PubMed: 32074971
DOI: 10.3390/cells9020440 -
FASEB Journal : Official Publication of... May 2023Associative learning and memory are fundamental behavioral processes through which organisms adapt to complex environments. Associative memory involves long-lasting... (Review)
Review
Associative learning and memory are fundamental behavioral processes through which organisms adapt to complex environments. Associative memory involves long-lasting changes in synaptic plasticity. Dendritic spines are tiny protrusions from the dendritic shaft of principal neurons, providing the structural basis for synaptic plasticity and brain networks in response to external stimuli. Mounting evidence indicates that dendritic spine dynamics are crucial in different associative memory phases, including acquisition, consolidation, and reconsolidation. Causally bridging dendritic spine dynamics and associative memory is still limited by the suitable tools to measure and control spine dynamics in vivo under behaviorally relevant conditions. Here, we review data providing evidence for the remodeling of dendritic spines during associative memory processing and outline open questions.
Topics: Dendritic Spines; Neuronal Plasticity; Brain; Memory; Neurons; Synapses
PubMed: 37000506
DOI: 10.1096/fj.202202166R -
Biophysical Journal Nov 2023Dendritic spines are small protrusions that mediate most of the excitatory synaptic transmission in the brain. Initially, the anatomical structure of spines has... (Review)
Review
Dendritic spines are small protrusions that mediate most of the excitatory synaptic transmission in the brain. Initially, the anatomical structure of spines has suggested that they serve as isolated biochemical and electrical compartments. Indeed, following ample experimental evidence, it is now widely accepted that a significant physiological role of spines is to provide biochemical compartmentalization in signal integration and plasticity in the nervous system. In contrast to the clear biochemical role of spines, their electrical role is uncertain and is currently being debated. This is mainly because spines are small and not accessible to conventional experimental methods of electrophysiology. Here, I focus on reviewing the literature on the electrical properties of spines, including the initial morphological and theoretical modeling studies, indirect experimental approaches based on measurements of diffusional resistance of the spine neck, indirect experimental methods using two-photon uncaging of glutamate on spine synapses, optical imaging of intracellular calcium concentration changes, and voltage imaging with organic and genetically encoded voltage-sensitive probes. The interpretation of evidence from different preparations obtained with different methods has yet to reach a consensus, with some analyses rejecting and others supporting an electrical role of spines in regulating synaptic signaling. Thus, there is a need for a critical comparison of the advantages and limitations of different methodological approaches. The only experimental study on electrical signaling monitored optically with adequate sensitivity and spatiotemporal resolution using voltage-sensitive dyes concluded that mushroom spines on basal dendrites of cortical pyramidal neurons in brain slices have no electrical role.
Topics: Dendritic Spines; Dendrites; Pyramidal Cells; Synaptic Transmission; Glutamic Acid; Synapses
PubMed: 37837192
DOI: 10.1016/j.bpj.2023.10.008 -
Progress in Neuro-psychopharmacology &... Jun 2018Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the shape and size of... (Review)
Review
Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the shape and size of dendritic spines correlate with the functional changes in excitatory synapses and are heavily dependent on the remodeling of the underlying actin cytoskeleton. Recent evidence implicates synapses at dendritic spines as important substrates of pathogenesis in neuropsychiatric disorders, including autism spectrum disorder (ASD). Although synaptic perturbations are not the only alterations relevant for these diseases, understanding the molecular underpinnings of the spine and synapse pathology may provide insight into their etiologies and could reveal new drug targets. In this review, we will discuss recent findings of defective actin regulation in dendritic spines associated with ASD.
Topics: Actin Cytoskeleton; Animals; Autism Spectrum Disorder; Dendritic Spines; Humans; Synapses
PubMed: 28870634
DOI: 10.1016/j.pnpbp.2017.08.023 -
Human Vaccines & Immunotherapeutics Nov 2022Bacillus Calmette - Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic...
Bacillus Calmette - Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with Alzheimer's disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of -JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.
Topics: Animals; Mice; Alzheimer Disease; Dendritic Spines; Disease Models, Animal; Hippocampus; Interleukin-4; Mice, Transgenic; BCG Vaccine; Dendrites; Tumor Necrosis Factor-alpha
PubMed: 36113067
DOI: 10.1080/21645515.2022.2121568 -
Seminars in Cell & Developmental Biology May 2018Dendritic spines are actin-rich, postsynaptic protrusions that contact presynaptic terminals to form excitatory chemical synapses. These synaptic contacts are widely... (Review)
Review
Dendritic spines are actin-rich, postsynaptic protrusions that contact presynaptic terminals to form excitatory chemical synapses. These synaptic contacts are widely believed to be the sites of memory formation and information storage, and changes in spine shape are thought to underlie several forms of learning-related plasticity. Both membrane trafficking pathways and the actin cytoskeleton drive activity-dependent structural and functional changes in dendritic spines. A key molecular player in regulating these processes is the activity-regulated cytoskeleton-associated protein (Arc), a protein that has diverse roles in expression of synaptic plasticity. In this review, we highlight important findings that have shaped our understanding of Arc's functions in structural and functional plasticity, as well as Arc's contributions to memory consolidation and disease.
Topics: Actins; Cytoskeletal Proteins; Dendritic Spines; Endocytosis; Humans; Memory; Nerve Tissue Proteins; Neuronal Plasticity; Synapses
PubMed: 28943393
DOI: 10.1016/j.semcdb.2017.09.022 -
Journal of Molecular Neuroscience : MN Oct 2023Dendritic spines are small, dynamic protrusions along the dendrite that comprise more than 90% of excitatory connections in the brain, making them essential sites for...
Dendritic spines are small, dynamic protrusions along the dendrite that comprise more than 90% of excitatory connections in the brain, making them essential sites for neuronal communication. These synaptic sites change throughout the process of development, reducing in density and shifting morphology as synapses are refined. One important class of dendritic spine regulators is microRNA (miRNA), small-noncoding RNAs that post-transcriptionally regulate gene expression. Several studies suggest that miRNA-324-5p regulates dendritic spine formation. In addition, we have previously shown that miR-324-5p plays a role in seizure and long-term potentiation, both of which involve dendritic spine changes. In this study, we aimed to characterize the role of miRNA-324-5p in developmental spine regulation by assessing the effect of Mir324 knockout (KO) on dendritic spine density and expression of a subset of dendritic proteins at select developmental time points. We show that miR-324-5p expression is developmentally regulated and peaks at 4 weeks of age. We demonstrate that loss of miR-324-5p expression leads to differential changes in both target protein expression and spine density at different time points during development, disrupting the pattern of spine density changes and leading to a premature loss of dendritic spines in KO mice, which is compensated later. Our findings indicate that miR-324-5p plays a role in synaptic refinement across development. Additionally, our data illustrate the importance of context in the study of miRNA, as regulation by and/or of miRNA can vary dramatically across development and in disease.
Topics: Animals; Mice; Dendritic Spines; Mice, Knockout; MicroRNAs; Neurons; Synapses
PubMed: 37773316
DOI: 10.1007/s12031-023-02157-4