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Neuron Aug 2021Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the...
Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and timescale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine size and density, driven by an elevated spine formation rate. The structural remodeling occurred quickly within 24 h and was persistent 1 month later. Psilocybin also ameliorated stress-related behavioral deficit and elevated excitatory neurotransmission. Overall, the results demonstrate that psilocybin-evoked synaptic rewiring in the cortex is fast and enduring, potentially providing a structural trace for long-term integration of experiences and lasting beneficial actions.
Topics: Animals; Cerebral Cortex; Dendrites; Dendritic Spines; Female; Frontal Lobe; Male; Mice; Neuronal Plasticity; Psilocybin; Pyramidal Cells; Synaptic Transmission
PubMed: 34228959
DOI: 10.1016/j.neuron.2021.06.008 -
Nature Sep 2022Neurons are highly polarized cells that face the fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function properly. The...
Neurons are highly polarized cells that face the fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function properly. The axon initial segment (AIS) is a specialized domain that separates a neuron's morphologically, biochemically and functionally distinct axon and dendrite compartments. How the AIS maintains polarity between these compartments is not fully understood. Here we find that in Caenorhabditis elegans, mouse, rat and human neurons, dendritically and axonally polarized transmembrane proteins are recognized by endocytic machinery in the AIS, robustly endocytosed and targeted to late endosomes for degradation. Forcing receptor interaction with the AIS master organizer, ankyrinG, antagonizes receptor endocytosis in the AIS, causes receptor accumulation in the AIS, and leads to polarity deficits with subsequent morphological and behavioural defects. Therefore, endocytic removal of polarized receptors that diffuse into the AIS serves as a membrane-clearance mechanism that is likely to work in conjunction with the known AIS diffusion-barrier mechanism to maintain neuronal polarity on the plasma membrane. Our results reveal a conserved endocytic clearance mechanism in the AIS to maintain neuronal polarity by reinforcing axonal and dendritic compartment membrane boundaries.
Topics: Animals; Axon Initial Segment; Caenorhabditis elegans; Cell Membrane; Cell Polarity; Dendrites; Diffusion; Endocytosis; Endosomes; Humans; Mice; Protein Transport; Proteolysis; Rats; Receptors, Cell Surface
PubMed: 35978188
DOI: 10.1038/s41586-022-05074-5 -
Current Osteoporosis Reports Dec 2022The purpose of this review is to discuss the molecular mechanisms involved in osteocyte dendrite formation, summarize the similarities between osteocytic and neuronal... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to discuss the molecular mechanisms involved in osteocyte dendrite formation, summarize the similarities between osteocytic and neuronal projections, and highlight the importance of osteocyte dendrite maintenance in human skeletal disease.
RECENT FINDINGS
It is suggested that there is a causal relationship between the loss of osteocyte dendrites and the increased osteocyte apoptosis during conditions including aging, microdamage, and skeletal disease. A few mechanisms are proposed to control dendrite formation and outgrowth, such as via the regulation of actin polymerization dynamics. This review addresses the impact of osteocyte dendrites in bone health and disease. Recent advances in multi-omics, in vivo and in vitro models, and microscopy-based imaging have provided novel approaches to reveal the underlying mechanisms that regulate dendrite development. Future therapeutic approaches are needed to target the process of osteocyte dendrite formation.
Topics: Humans; Osteocytes; Bone and Bones; Aging; Dendrites
PubMed: 36087214
DOI: 10.1007/s11914-022-00753-8 -
Developmental Neurobiology Apr 2017Dendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size, and morphology are some of... (Review)
Review
Dendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size, and morphology are some of the crucial factors determining how signals coming from individual synapses are integrated. Much remains to be understood about the characteristics of neuronal dendrites and dendritic spines in autism and related disorders. Although there have been many studies conducted using autism mouse models, few have been carried out using postmortem human tissue from patients. Available animal models of autism include those generated through genetic modifications and those non-genetic models of the disease. Here, we review how dendrite and spine morphology and number is affected in autism and related neurodevelopmental diseases, both in human, and genetic and non-genetic animal models of autism. Overall, data obtained from human and animal models point to a generalized reduction in the size and number, as well as an alteration of the morphology of dendrites; and an increase in spine densities with immature morphology, indicating a general spine immaturity state in autism. Additional human studies on dendrite and spine number and morphology in postmortem tissue are needed to understand the properties of these structures in the cerebral cortex of patients with autism. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.
Topics: Animals; Autism Spectrum Disorder; Cerebral Cortex; Dendrites; Dendritic Spines; Disease Models, Animal; Humans
PubMed: 27390186
DOI: 10.1002/dneu.22417 -
Current Opinion in Neurobiology Aug 2014Pruning, a process by which neurons selectively remove exuberant or unnecessary processes without causing cell death, is crucial for the establishment of mature neural... (Review)
Review
Pruning, a process by which neurons selectively remove exuberant or unnecessary processes without causing cell death, is crucial for the establishment of mature neural circuits during animal development. Yet relatively little is known about molecular and cellular mechanisms that govern neuronal pruning. Holometabolous insects, such as Drosophila, undergo complete metamorphosis and their larval nervous systems are replaced with adult-specific ones, thus providing attractive models for studying neuronal pruning. Drosophila mushroom body and dendritic arborization neurons have been utilized as two appealing systems to elucidate the underlying mechanisms of axon and dendrite pruning, respectively. In this review we highlight recent developments and discuss some similarities and differences in the mechanisms that regulate these two distinct modes of neuronal pruning in Drosophila.
Topics: Animals; Axons; Dendrites; Drosophila; Models, Animal; Nervous System; Neurons
PubMed: 24793180
DOI: 10.1016/j.conb.2014.04.005 -
Current Opinion in Neurobiology Dec 2018Dendrites are the conduits for receiving (and in some cases transmitting) neural signals; their ability to do these jobs is a direct result of their morphology.... (Review)
Review
Dendrites are the conduits for receiving (and in some cases transmitting) neural signals; their ability to do these jobs is a direct result of their morphology. Developmental patterning mechanisms are critical to ensuring concordance between dendritic form and function. This article reviews recent studies in vertebrate retina and brain that elucidate key strategies for dendrite functional maturation. Specific cellular and molecular signals control the initiation and elaboration of dendritic arbors, and facilitate integration of young neurons into particular circuits. In some cells, dendrite growth and remodeling continues into adulthood. Once formed, dendrites subdivide into compartments with distinct physiological properties that enable dendritic computations. Understanding these key stages of dendrite patterning will help reveal how circuit functional properties arise during development.
Topics: Amacrine Cells; Animals; Dendrites; Humans; Morphogenesis; Nerve Net; Neuronal Plasticity
PubMed: 30092409
DOI: 10.1016/j.conb.2018.07.007 -
Nature Reviews. Neuroscience Aug 2013In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain... (Review)
Review
In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain are stable for months, years and possibly even decades. Emerging evidence reveals that dendritic spine and dendrite arbor stability have crucial roles in the correct functioning of the adult brain and that loss of stability is associated with psychiatric disorders and neurodegenerative diseases. Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease.
Topics: Alzheimer Disease; Animals; Dendrites; Dendritic Spines; Humans; Models, Neurological; Neuronal Plasticity; Neurons; Signal Transduction; Stroke; Synapses
PubMed: 23839597
DOI: 10.1038/nrn3486 -
Annual Review of Neuroscience 2010Emerging evidence indicates that once established, synapses and dendrites can be maintained for long periods, if not for the organism's entire lifetime. In contrast to... (Review)
Review
Emerging evidence indicates that once established, synapses and dendrites can be maintained for long periods, if not for the organism's entire lifetime. In contrast to the wealth of knowledge regarding axon, dendrite, and synapse development, we understand comparatively little about the cellular and molecular mechanisms that enable long-term synapse and dendrite maintenance. Here, we review how the actin cytoskeleton and its regulators, adhesion receptors, and scaffolding proteins mediate synapse and dendrite maintenance. We examine how these mechanisms are reinforced by trophic signals passed between the pre- and postsynaptic compartments. We also discuss how synapse and dendrite maintenance mechanisms are compromised in psychiatric and neurodegenerative disorders.
Topics: Animals; Dendrites; Humans; Mental Disorders; Neurodegenerative Diseases; Synapses
PubMed: 20367247
DOI: 10.1146/annurev-neuro-060909-153204 -
Hormones and Behavior Mar 2012For most people, their quality of life depends on their successful interdependence with others, which requires sophisticated social cognition, communication, and... (Review)
Review
For most people, their quality of life depends on their successful interdependence with others, which requires sophisticated social cognition, communication, and emotional bonds. Across the lifespan, new bonds must be forged and maintained, and conspecific menaces must be managed. The dynamic nature of the human social landscape suggests ongoing specific alterations in neural circuitry across several brain systems to subserve social behavior. To discover the biological mechanisms that contribute to normal social activities, animal models of social behavior have been developed. One valuable model system has been female rat sexual behavior, which is governed by cyclic variation of ovarian hormones. This behavior is modulated by the neuropeptide oxytocin (OT) through its actions in the hypothalamic ventromedial nucleus (VMH). The fluctuation of this behavior is associated with dendrite remodeling, like several other examples of behavioral plasticity. This review compares hormone-induced plasticity in the VMH with other examples of dendrite plasticity across the mammalian nervous system, namely the neurobehavioral paradigms of environmental enrichment, chronic stress, and incentive sensitization, which affect the neocortex, hippocampal formation, and ventral striatum, respectively. This comparison suggests that the effects of ovarian hormones on VMH neurons in rats, given the simple dendritic arbor and short time course for dendrite remodeling, provide a dual opportunity for mechanistic and functional studies that will shed light on i) the neural actions of OT that regulate social behavior and, ii) behaviorally relevant dendrite regulation in a variety of brain structures. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.
Topics: Animals; Dendrites; Emotions; Environment; Female; Humans; Hypothalamus; Male; Neuronal Plasticity; Oxytocin; Rats; Sexual Behavior; Sexual Behavior, Animal; Social Behavior; Ventromedial Hypothalamic Nucleus
PubMed: 22326383
DOI: 10.1016/j.yhbeh.2012.01.012 -
Developmental Biology Jul 2019A neuron's contribution to the information flow within a neural circuit is governed by the structure of its dendritic arbor. The geometry of the dendritic arbor directly... (Review)
Review
A neuron's contribution to the information flow within a neural circuit is governed by the structure of its dendritic arbor. The geometry of the dendritic arbor directly determines synaptic density and the size of the receptive field, both of which influence the firing pattern of the neuron. Importantly, the position of individual dendritic branches determines the identity of the neuron's presynaptic partner and thus the nature of the incoming sensory information. To generate the unique stereotypic architecture of a given neuronal subtype, nascent branches must emerge from the dendritic shaft at preprogramed branch points. Subsequently, a complex array of extrinsic factors regulates the degree and orientation of branch expansion to ensure maximum coverage of the receptive field whilst constraining growth within predetermined territories. In this review we focus on studies that best illustrate how environmental cues such as the Wnts and Netrins and their receptors sculpt the dendritic arbor. We emphasize the pivotal role played by the actin cytoskeleton and its upstream regulators in branch initiation, outgrowth and navigation. Finally, we discuss how protocadherin and DSCAM contact-mediated repulsion prevents inappropriate synapse formation between sister dendrites or dendrites and the axon from the same neuron. Together these studies highlight the clever ways evolution has solved the problem of constructing complex branch geometries.
Topics: Animals; Dendrites; Humans; Neurogenesis; Neuronal Plasticity; Synapses
PubMed: 30550882
DOI: 10.1016/j.ydbio.2018.12.005