-
Nature Reviews. Neuroscience Nov 2021The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or... (Review)
Review
The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.
Topics: Animals; Axons; Dendrites; Humans; Neuronal Plasticity; Neurons; Peripheral Nervous System Diseases; Sympathetic Nervous System
PubMed: 34599308
DOI: 10.1038/s41583-021-00523-y -
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 -
Current Opinion in Neurobiology Aug 2021Neuronal dendrites acquire complex morphologies during development. These are not just the product of cell-intrinsic developmental programs; rather they are defined in... (Review)
Review
Neuronal dendrites acquire complex morphologies during development. These are not just the product of cell-intrinsic developmental programs; rather they are defined in close interaction with the cellular environment. Thus, to understand the molecular cascades that yield appropriate morphologies, it is essential to investigate them in vivo, in the actual complex tissue environment encountered by the differentiating neuron in the developing animal. Particularly, genetic approaches have pointed to factors controlling dendrite differentiation in vivo. These suggest that localized and transient molecular cascades might underlie the formation and stabilization of dendrite branches with neuron type-specific characteristics. Here, I highlight the need for studies of neuronal dendrite differentiation in the animal, the challenges provided by such an approach, and the promising pathways that have recently opened.
Topics: Animals; Dendrites; Neurons
PubMed: 34134010
DOI: 10.1016/j.conb.2021.05.001 -
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 -
Genetics Jun 2024Since the days of Ramón y Cajal, the vast diversity of neuronal and particularly dendrite morphology has been used to catalog neurons into different classes. Dendrite... (Review)
Review
Since the days of Ramón y Cajal, the vast diversity of neuronal and particularly dendrite morphology has been used to catalog neurons into different classes. Dendrite morphology varies greatly and reflects the different functions performed by different types of neurons. Significant progress has been made in our understanding of how dendrites form and the molecular factors and forces that shape these often elaborately sculpted structures. Here, we review work in the nematode Caenorhabditis elegans that has shed light on the developmental mechanisms that mediate dendrite morphogenesis with a focus on studies investigating ciliated sensory neurons and the highly elaborated dendritic trees of somatosensory neurons. These studies, which combine time-lapse imaging, genetics, and biochemistry, reveal an intricate network of factors that function both intrinsically in dendrites and extrinsically from surrounding tissues. Therefore, dendrite morphogenesis is the result of multiple tissue interactions, which ultimately determine the shape of dendritic arbors.
Topics: Animals; Caenorhabditis elegans; Dendrites; Morphogenesis; Caenorhabditis elegans Proteins; Sensory Receptor Cells
PubMed: 38785371
DOI: 10.1093/genetics/iyae056 -
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 -
Developmental Biology Jun 2022Many membrane proteins are highly enriched in either dendrites or axons. This non-uniform distribution is a critical feature of neuronal polarity and underlies neuronal... (Review)
Review
Many membrane proteins are highly enriched in either dendrites or axons. This non-uniform distribution is a critical feature of neuronal polarity and underlies neuronal function. The molecular mechanisms responsible for polarized distribution of membrane proteins has been studied for some time and many answers have emerged. A less well studied feature of neurons is that organelles are also frequently non-uniformly distributed. For instance, EEA1-positive early endosomes are somatodendritic whereas synaptic vesicles are axonal. In addition, some organelles are present in both axons and dendrites, but not distributed uniformly along the processes. One well known example are lysosomes which are abundant in the soma and proximal dendrite, but sparse in the distal dendrite and the distal axon. The mechanisms that determine the spatial distribution of organelles along dendrites are only starting to be studied. In this review, we will discuss the cell biological mechanisms of how the distribution of diverse sets of endosomes along the proximal-distal axis of dendrites might be regulated. In particular, we will focus on the regulation of bulk homeostatic mechanisms as opposed to local regulation. We posit that immature dendrites regulate organelle motility differently from mature dendrites in order to spatially organize dendrite growth, branching and sculpting.
Topics: Axons; Dendrites; Endosomes; Membrane Proteins; Neurons
PubMed: 35306006
DOI: 10.1016/j.ydbio.2022.03.004 -
Journal of Neurochemistry Jun 2017Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate... (Review)
Review
Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate of depolymerization. Moreover, the characteristic morphology of drebrin-decorated F-actin enables it to respond differently to the same signals from other actin cytoskeletons. Drebrin consists of two major isoforms, drebrin E and drebrin A. In the developing brain, drebrin E appears in migrating neurons and accumulates in the growth cones of axons and dendrites. Drebrin E-decorated F-actin links lamellipodium F-actin to microtubules in the growth cones. Then drebrin A appears at nascent synapses and drebrin A-decorated F-actin facilitates postsynaptic molecular assembly. In the adult brain, drebrin A-decorated F-actin is concentrated in the central region of dendritic spines. During long-term potentiation initiation, NMDA receptor-mediated Ca influx induces the transient exodus of drebrin A-decorated F-actin via myosin II ATPase activation. Because of the unique physical characteristics of drebrin A-decorated F-actin, this exodus likely contributes to the facilitation of F-actin polymerization and spine enlargement. Additionally, drebrin reaccumulation in dendritic spines is observed after the exodus. In our drebrin exodus model of structure-based synaptic plasticity, reestablishment of drebrin A-decorated F-actin is necessary to keep the enlarged spine size during long-term potentiation maintenance. In this review, we introduce the genetic and biochemical properties of drebrin and the roles of drebrin in early stage of brain development, synaptic formation and synaptic plasticity. Further, we discuss the pathological relevance of drebrin loss in Alzheimer's disease. This article is part of the mini review series "60th Anniversary of the Japanese Society for Neurochemistry".
Topics: Animals; Dendrites; Dendritic Spines; Humans; Long-Term Potentiation; Neuronal Plasticity; Neurons; Synapses
PubMed: 28199019
DOI: 10.1111/jnc.13988 -
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 -
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