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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 Topics in Developmental Biology 2021Neurons develop dendritic morphologies that bear cell type-specific features in dendritic field size and geometry, branch placement and density, and the types and... (Review)
Review
Neurons develop dendritic morphologies that bear cell type-specific features in dendritic field size and geometry, branch placement and density, and the types and distributions of synaptic contacts. Dendritic patterns influence the types and numbers of inputs a neuron receives, and the ways in which neural information is processed and transmitted in the circuitry. Even subtle alterations in dendritic structures can have profound consequences on neuronal function and are implicated in neurodevelopmental disorders. In this chapter, I review how growing dendrites acquire their exquisite patterns by drawing examples from diverse neuronal cell types in vertebrate and invertebrate model systems. Dendrite morphogenesis is shaped by intrinsic and extrinsic factors such as transcriptional regulators, guidance and adhesion molecules, neighboring cells and synaptic partners. I discuss molecular mechanisms that regulate dendrite morphogenesis with a focus on five aspects of dendrite patterning: (1) Dendritic cytoskeleton and cellular machineries that build the arbor; (2) Gene regulatory mechanisms; (3) Afferent cues that regulate dendritic arbor growth; (4) Space-filling strategies that optimize dendritic coverage; and (5) Molecular cues that specify dendrite wiring. Cell type-specific implementation of these patterning mechanisms produces the diversity of dendrite morphologies that wire the nervous system.
Topics: Dendrites; Morphogenesis
PubMed: 33706919
DOI: 10.1016/bs.ctdb.2020.12.008 -
Current Opinion in Neurobiology Aug 2019Neurons exhibit a unique degree of spatial compartmentalization and are able to maintain and remodel their proteomes independently from the cell body. While much effort... (Review)
Review
Neurons exhibit a unique degree of spatial compartmentalization and are able to maintain and remodel their proteomes independently from the cell body. While much effort has been devoted to understanding the capacity and role for local protein synthesis in dendrites and spines, local mRNA translation in mature axons, projecting over distances up to a meter, has received much less attention. Also, little is known about the spatio-temporal dynamics of axonal and dendritic gene expression as function of mRNA abundance, protein synthesis and degradation. Here, we summarize key recent findings that have shaped our knowledge of the precise location of local protein production and discuss unique strategies used by neurons to shape presynaptic and postsynaptic proteomes.
Topics: Axons; Dendrites; RNA, Messenger
PubMed: 30861464
DOI: 10.1016/j.conb.2019.02.008 -
Current Opinion in Neurobiology Oct 2019Dendrites are much more than passive neuronal components. Mounting experimental evidence and decades of computational work have decisively shown that dendrites leverage... (Review)
Review
Dendrites are much more than passive neuronal components. Mounting experimental evidence and decades of computational work have decisively shown that dendrites leverage a host of nonlinear biophysical phenomena and actively participate in sophisticated computations, at the level of the single neuron and at the level of the network. However, a coherent view of their processing power is still lacking and dendrites are largely neglected in neural network models. Here, we describe four classes of dendritic information processing and delineate their implications at the algorithmic level. We propose that beyond the well-known spatiotemporal filtering of their inputs, dendrites are capable of selecting, routing and multiplexing information. By separating dendritic processing from axonal outputs, neuron networks gain a degree of freedom with implications for perception and learning.
Topics: Action Potentials; Dendrites; Learning; Models, Neurological; Neural Networks, Computer
PubMed: 31419712
DOI: 10.1016/j.conb.2019.07.006 -
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 Neuroendocrinology Nov 2021The unexpected observation that the long processes of gonadotrophin-releasing hormone (GnRH) neurons not only conducted action potentials, but also operated to integrate... (Review)
Review
The unexpected observation that the long processes of gonadotrophin-releasing hormone (GnRH) neurons not only conducted action potentials, but also operated to integrate afferent information at their distal-most extent gave rise to the concept of a blended dendritic-axonal process termed the "dendron". The proximal dendrites of the GnRH neuron function in a conventional manner, receiving synaptic inputs and initiating action potentials that are critical for the surge mode of GnRH secretion. The distal dendrons are regulated by both classical synapses and volume transmission and likely operate using subthreshold electrotonic propagation into the nearby axon terminals in the median eminence. Evidence indicates that neural processing at the distal dendron is responsible for the pulsatile patterning of GnRH secretion. Although the dendron remains unique to the GnRH neuron, data show that it exists in both mice and rats and may be a common feature of mammalian species in which GnRH neuron cell bodies do not migrate into the basal hypothalamus. This review outlines the discovery and function of the dendron as a unique neuronal structure optimised to generate episodic neuronal output.
Topics: Animals; Dendrimers; Dendrites; Gonadotropin-Releasing Hormone; Mammals; Mice; Neurons; Neuropeptides; Rats
PubMed: 34427000
DOI: 10.1111/jne.13024