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Neuroscience Research Sep 2022BAX is a Bcl-2 family protein acting on apoptosis. It also promotes mitochondrial fusion by interacting with the mitochondrial fusion protein Mitofusin (Mfn1 and Mfn2)....
BAX is a Bcl-2 family protein acting on apoptosis. It also promotes mitochondrial fusion by interacting with the mitochondrial fusion protein Mitofusin (Mfn1 and Mfn2). Neuronal mitochondria are important for the development and modification of dendritic spines, which are subcellular compartments accommodating excitatory synapses in postsynaptic neurons. The abundance of dendritic mitochondria influences dendritic spine development. Mitochondrial fusion is essential for mitochondrial homeostasis. Here, we show that in the hippocampal neuron of BAX knockout mice, mitochondrial fusion is impaired, leading to decreases in mitochondrial length and total mitochondrial mass in dendrites. Notably, BAX knockout mice also have fewer dendritic spines and less cellular Adenosine 5'triphosphate (ATP) in dendrites. The spine and ATP changes are abolished by restoring mitochondria fusion via overexpressing Mfn1 and Mfn2. These findings indicate that BAX-mediated mitochondrial fusion in neurons is crucial for the development of dendritic spines and the maintenance of cellular ATP levels.
Topics: Adenosine Triphosphate; Animals; Dendritic Spines; GTP Phosphohydrolases; Mice; Mitochondrial Dynamics; Mitochondrial Proteins; bcl-2-Associated X Protein
PubMed: 35688289
DOI: 10.1016/j.neures.2022.06.002 -
The Journal of Physiology Jan 2010In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and... (Review)
Review
In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and hippocampus, dendritic spines are heterogeneous in shape. It has been shown that the shapes of the spine can affect synapse stability and synaptic function. Dendritic spines are highly motile structures that can undergo actin-dependent shape changes, which occur over a time scale ranging from seconds to tens of minutes or even days. The formation, remodelling and elimination of excitatory synapses on dendritic spines represent ways of refining the microcircuitry in the brain. Here I review the current knowledge on the effects of modulation of AMPA and NMDA ionotropic glutamate receptors on dendritic spine formation, motility and remodelling.
Topics: Animals; Brain; Dendritic Spines; Excitatory Amino Acids; Excitatory Postsynaptic Potentials; Humans; Neuronal Plasticity; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 19933758
DOI: 10.1113/jphysiol.2009.178905 -
ACS Chemical Neuroscience May 2023Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new... (Review)
Review
Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new techniques develop, it is not always clear when and how each may be used to answer specific scientific questions posed. Dendritic spines, which are often indicative of synapse formation and neural plasticity, have been implicated across many brain regions in neurodevelopmental disorders as a marker for neural changes reflecting neural dysfunction or alterations. In this Perspective we highlight several techniques for staining, imaging, and quantifying dendritic spines as well as provide a framework for avoiding potential issues related to pseudoreplication. This framework illustrates how others may apply the most rigorous approaches. We consider the cost-benefit analysis of the varied techniques, recognizing that the most sophisticated equipment may not always be necessary for answering some research questions. Together, we hope this piece will help researchers determine the best strategy toward using the ever-growing number of techniques available to determine neural changes underlying dendritic spine morphology in health and neurodevelopmental disorders.
Topics: Humans; Dendritic Spines; Neurodevelopmental Disorders; Neuronal Plasticity; Brain
PubMed: 37070364
DOI: 10.1021/acschemneuro.3c00062 -
The Journal of Neuroscience : the... Jul 2014Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination of synapses and associated...
Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination of synapses and associated dendritic spines to form functional networks. The correct balance of these processes is thought to be regulated by synapse-specific changes in the subunit composition of NMDA-type glutamate receptors (NMDARs). Among these, the nonconventional NMDAR subunit GluN3A has been suggested to play a role as a molecular brake in synaptic maturation. We tested here this hypothesis using confocal time-lapse imaging in rat hippocampal organotypic slices and assessed the role of GluN3A-containing NMDARs on spine dynamics. We found that overexpressing GluN3A reduced spine density over time, increased spine elimination, and decreased spine stability. The effect of GluN3A overexpression could be further enhanced by using an endocytosis-deficient GluN3A mutant and reproduced by silencing the adaptor protein PACSIN1, which prevents the endocytosis of endogenous GluN3A. Conversely, silencing of GluN3A reduced spine elimination and favored spine stability. Moreover, reexpression of GluN3A in more mature tissue reinstated an increased spine pruning and a low spine stability. Mechanistically, the decreased stability in GluN3A overexpressing neurons could be linked to a failure of plasticity-inducing protocols to selectively stabilize spines and was dependent on the ability of GluN3A to bind the postsynaptic scaffold GIT1. Together, these data provide strong evidence that GluN3A prevents the activity-dependent stabilization of synapses thereby promoting spine pruning, and suggest that GluN3A expression operates as a molecular signal for controlling the extent and timing of synapse maturation.
Topics: Action Potentials; Aging; Animals; Animals, Newborn; Cells, Cultured; Dendritic Spines; Female; Hippocampus; Male; Membrane Glycoproteins; Neuronal Plasticity; Rats; Synaptic Transmission
PubMed: 25009255
DOI: 10.1523/JNEUROSCI.5183-13.2014 -
Neuroscience Aug 2022Dendritic spines are small protrusions on dendrites that serve as the postsynaptic site of the majority of excitatory synapses. These structures are important for normal... (Comparative Study)
Comparative Study
Dendritic spines are small protrusions on dendrites that serve as the postsynaptic site of the majority of excitatory synapses. These structures are important for normal synaptic transmission, and alterations in their density and morphology have been documented in various disease states. Over 130 years ago, Ramón y Cajal used Golgi-stained tissue sections to study dendritic morphology. Despite the array of technological advances, including iontophoretic microinjection of Lucifer yellow (LY) fluorescent dye, Golgi staining continues to be one of the most popular approaches to visualize dendritic spines. Here, we compared dendritic spine density and morphology among pyramidal neurons in layers 2/3 of the mouse medial prefrontal cortex (mPFC) and pyramidal neurons in hippocampal CA1 using three-dimensional digital reconstructions of (1) brightfield microscopy z-stacks of Golgi-impregnated dendrites and (2) confocal microscopy z-stacks of LY-filled dendrites. Analysis of spine density revealed that the LY microinjection approach enabled detection of approximately three times as many spines as the Golgi staining approach in both brain regions. Spine volume measurements were larger using Golgi staining compared to LY microinjection in both mPFC and CA1. Spine length was mostly comparable between techniques in both regions. In the mPFC, head diameter was similar for Golgi staining and LY microinjection. However, in CA1, head diameter was approximately 50% smaller on LY-filled dendrites compared to Golgi staining. These results indicate that Golgi staining and LY microinjection yield different spine density and morphology measurements, with Golgi staining failing to detect dendritic spines and overestimating spine size.
Topics: Animals; Dendrites; Dendritic Spines; Hippocampus; Isoquinolines; Mice; Pyramidal Cells
PubMed: 35752428
DOI: 10.1016/j.neuroscience.2022.06.029 -
The Journal of Comparative Neurology Dec 2016The stress-responsive hypothalamo-pituitary-adrenal (HPA) axis plays a central role in promoting adaptations acutely, whereas adverse effects on physiology and behavior...
The stress-responsive hypothalamo-pituitary-adrenal (HPA) axis plays a central role in promoting adaptations acutely, whereas adverse effects on physiology and behavior following chronic challenges may result from overactivity of this system. Elevations in glucocorticoids, the end-products of HPA activation, play roles in adaptive and maladaptive processes by targeting cognate receptors throughout neurons in limbic cortical networks to alter synaptic functioning. Because previous work has shown that chronic stress leads to functionally relevant regressive alterations in dendritic spine shape and number in pyramidal neurons in the medial prefrontal cortex (mPFC), this study examines the capacity of sustained increases in circulating corticosterone (B) alone to alter dendritic spine morphology and density in this region. Subcutaneous B pellets were implanted in rats to provide continuous exposure to levels approximating the circadian mean or peak of the steroid for 1, 2, or 3 weeks. Pyramidal neurons in the prelimbic area of the mPFC were selected for intracellular fluorescent dye filling, followed by high-resolution three-dimensional imaging and analysis of dendritic arborization and spine morphometry. Two or more weeks of B exposure decreased dendritic spine volume in the mPFC, whereas higher dose exposure of the steroid resulted in apical dendritic retraction and spine loss in the same cell population, with thin spine subtypes showing the greatest degree of attrition. Finally, these structural alterations were noted to persist following a 3-week washout period and corresponding restoration of circadian HPA rhythmicity. These studies suggest that prolonged disruptions in adrenocortical functioning may be sufficient to induce enduring regressive structural and functional alterations in the mPFC. J. Comp. Neurol. 524:3729-3746, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cell Size; Corticosterone; Dendritic Spines; Dose-Response Relationship, Drug; Drug Implants; Fluorescent Dyes; Imaging, Three-Dimensional; Male; Microscopy, Confocal; Microscopy, Fluorescence; Models, Animal; Neuronal Plasticity; Prefrontal Cortex; Pyramidal Cells; Radioimmunoassay; Rats, Sprague-Dawley; Stress, Psychological
PubMed: 27113541
DOI: 10.1002/cne.24027 -
Molecular Autism May 2020Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has... (Review)
Review
Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgenic mice that model different monogenetic causes of ASD. A number of ASD-associated genetic variants are known to disrupt dendritic local protein synthesis, which is essential for spine morphogenesis, synaptic transmission, and plasticity. Most of our understanding on the molecular mechanism underlying ASD depends on studies using rodents. However, recent advance in human pluripotent stem cells and their neural differentiation provides a powerful alternative tool to understand the cellular aspects of human neurological disorders. In this review, we summarize recent progress on studying mRNA targeting and local protein synthesis in stem cell-derived neurons, and discuss how perturbation of these processes may impact synapse development and functions that are relevant to cognitive deficits in ASD.
Topics: Animals; Autism Spectrum Disorder; Biomarkers; Cell Differentiation; Dendritic Spines; Disease Susceptibility; Gene Expression Regulation; Humans; Morphogenesis; Mutation; Neurons; Pluripotent Stem Cells; Protein Biosynthesis; RNA, Messenger
PubMed: 32460854
DOI: 10.1186/s13229-020-00349-y -
Current Opinion in Neurobiology Jun 2012Dendritic spines are small mushroom-like protrusions arising from neurons where most excitatory synapses reside. Their peculiar shape suggests that spines can serve as... (Review)
Review
Dendritic spines are small mushroom-like protrusions arising from neurons where most excitatory synapses reside. Their peculiar shape suggests that spines can serve as an autonomous postsynaptic compartment that isolates chemical and electrical signaling. How neuronal activity modifies the morphology of the spine and how these modifications affect synaptic transmission and plasticity are intriguing issues. Indeed, the induction of long-term potentiation (LTP) or depression (LTD) is associated with the enlargement or shrinkage of the spine, respectively. This structural plasticity is mainly controlled by actin filaments, the principal cytoskeletal component of the spine. Here we review the pioneering microscopic studies examining the structural plasticity of spines and propose how changes in actin treadmilling might regulate spine morphology.
Topics: Animals; Dendritic Spines; Models, Biological; Neuronal Plasticity; Neurons; Ultrasonography
PubMed: 21963169
DOI: 10.1016/j.conb.2011.09.002 -
Brain Research Feb 2022Post-weaning social isolation stress has been shown to increase addiction-like behavior in adulthood. These long-term behavioral alterations may be due to long lasting...
Post-weaning social isolation stress has been shown to increase addiction-like behavior in adulthood. These long-term behavioral alterations may be due to long lasting isolation-induced structural changes to neurons in brain regions involved in reward processing. Previous studies have shown that various stressors alter dendritic spine density in the prefrontal cortex (PFC) and the nucleus accumbens, though many of these studies examine the short-term effects of stress, and are primarily conducted in males. There is mounting evidence that males and females exhibit differences in their stress responses, with some studies showing sex differences in stress-induced plasticity. To determine the long-lasting, sex-specific alterations in spine density following post-weaning social isolation, male and female mice were either isolated or group housed at weaning and spine density was measured once they reached adulthood. Post-weaning isolation increased spine density in the PFC of both the males and females, although the effects in the infralimbic cortex were more pronounced in the females. In the nucleus accumbens, adolescent isolation increased spine density in males only in the core and shell. Females also had higher baseline spine density than males in the nucleus accumbens core. Together these data suggest that adolescent social isolation causes long-term, sex-specific alterations to the prefrontal cortex and the nucleus accumbens.
Topics: Animals; Animals, Newborn; Brain; Cerebral Cortex; Dendritic Spines; Female; Hippocampus; Male; Mice; Neurons; Nucleus Accumbens; Prefrontal Cortex; Reward; Sex Characteristics; Social Isolation; Stress, Psychological; Weaning
PubMed: 34932973
DOI: 10.1016/j.brainres.2021.147755 -
Physiology (Bethesda, Md.) Feb 2006Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in... (Review)
Review
Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in synaptic transmission and plasticity. Recent advances in imaging and molecular technologies reveal that spines are complex, dynamic structures that contain a dense array of cytoskeletal, transmembrane, and scaffolding molecules. Several neurological and psychiatric disorders exhibit dendritic spine abnormalities.
Topics: Animals; Cytoskeleton; Dendrites; Dendritic Spines; Humans; Nervous System Diseases; Neuronal Plasticity; Signal Transduction; Synapses; Synaptic Transmission; rho GTP-Binding Proteins
PubMed: 16443821
DOI: 10.1152/physiol.00042.2005