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Anatomical Record (Hoboken, N.J. : 2007) Mar 2019The VIII nerve is formed by sensory neurons that innervate the inner ear, i.e., the vestibular and the auditory receptors. Neurons of the auditory portion, the cochlear... (Review)
Review
The VIII nerve is formed by sensory neurons that innervate the inner ear, i.e., the vestibular and the auditory receptors. Neurons of the auditory portion, the cochlear afferent fibers that innervate the sensory hair cells of the organ of Corti, have their somas in the cochlear spiral ganglion where two types of neurons can be distinguished. Afferent Type-I neurons are the 95% of the total population. Bipolar and myelinated fibers, each one innervates only one cochlear inner hair cell (IHC). In contrast, afferent Type-II neurons are only the 5% of the spiral ganglion population. They are pseudounipolar and unmyelinated fibers and innervate the cochlear outer hair cells (OHC) so that one afferent Type-II fiber contacts with multiple OHCs, but each OHC only receives one contact from one Type-II neuron. Both types of VIII nerve fibers are glutamatergic, but these asymmetric innervations of the cochlear sensory cells could suggest that the IHC codifies the truly auditory message but the OHC only informs about mechanical aspects of the state of the organ of Corti. In fact, the central nervous system (CNS) has control over the information transmitted by the Type-I neuron by means of axons from the superior olivary complex that innervate them to modulate, filter and/or inhibit the entry of auditory message to CNS. The aim of this paper is to review the current knowledge about the anatomy and physiology of the auditory portion of the VIII nerve. Anat Rec, 302:463-471, 2019. © 2018 Wiley Periodicals, Inc.
Topics: Afferent Pathways; Animals; Auditory Pathways; Axons; Cochlea; Cochlear Nerve; Hair Cells, Auditory; Mice; Mice, Inbred C57BL; Nerve Fibers; Neurons; Spiral Ganglion
PubMed: 29659185
DOI: 10.1002/ar.23815 -
Molecular Psychiatry Dec 2023While most of the efforts to uncover mechanisms contributing to bipolar disorder (BD) focused on phenotypes at the mature neuron stage, little research has considered...
While most of the efforts to uncover mechanisms contributing to bipolar disorder (BD) focused on phenotypes at the mature neuron stage, little research has considered events that may occur during earlier timepoints of neurodevelopment. Further, although aberrant calcium (Ca) signaling has been implicated in the etiology of this condition, the possible contribution of store-operated Ca entry (SOCE) is not well understood. Here, we report Ca and developmental dysregulations related to SOCE in BD patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells (BD-NPCs) and cortical-like glutamatergic neurons. First, using a Ca re-addition assay we found that BD-NPCs and neurons had attenuated SOCE. Intrigued by this finding, we then performed RNA-sequencing and uncovered a unique transcriptome profile in BD-NPCs suggesting accelerated neurodifferentiation. Consistent with these results, we measured a slower rate of proliferation, increased neurite outgrowth, and decreased size in neurosphere formations with BD-NPCs. Also, we observed decreased subventricular areas in developing BD cerebral organoids. Finally, BD NPCs demonstrated high expression of the let-7 family while BD neurons had increased miR-34a, both being microRNAs previously implicated in neurodevelopmental deviations and BD etiology. In summary, we present evidence supporting an accelerated transition towards the neuronal stage in BD-NPCs that may be indicative of early pathophysiological features of the disorder.
Topics: Induced Pluripotent Stem Cells; Neural Stem Cells; Bipolar Disorder; Humans; Cell Differentiation; Calcium Signaling; Calcium; Neurons; Neurogenesis; Organoids; MicroRNAs; Male; Transcriptome; Female
PubMed: 37402854
DOI: 10.1038/s41380-023-02152-6 -
Journal of Anatomy Aug 2023The precise specification of cellular fate is thought to ensure the production of the correct number of neurons within a population. Programmed cell death may be an... (Review)
Review
The precise specification of cellular fate is thought to ensure the production of the correct number of neurons within a population. Programmed cell death may be an additional mechanism controlling cell number, believed to refine the proper ratio of pre- to post-synaptic neurons for a given species. Here, we consider the size of three different neuronal populations in the rod pathway of the mouse retina: rod photoreceptors, rod bipolar cells, and AII amacrine cells. Across a collection of 28 different strains of mice, large variation in the numbers of all three cell types is present. The variation in their numbers is not correlated, so that the ratio of rods to rod bipolar cells, as well as rod bipolar cells to AII amacrine cells, varies as well. Establishing connectivity between such variable pre- and post-synaptic populations relies upon plasticity that modulates process outgrowth and morphological differentiation, which we explore experimentally for both rod bipolar and AII amacrine cells in a mouse retina with elevated numbers of each cell type. While both rod bipolar dendritic and axonal arbors, along with AII lobular arbors, modulate their areal size in relation to local homotypic cell densities, the dendritic appendages of the AII amacrine cells do not. Rather, these processes exhibit a different form of plasticity, regulating the branching density of their overlapping arbors. Each form of plasticity should ensure uniformity in retinal coverage in the presence of the independent specification of afferent and target cell number.
Topics: Mice; Animals; Dendrites; Retina; Amacrine Cells; Axons
PubMed: 35292986
DOI: 10.1111/joa.13653 -
Molecular Psychiatry Dec 2012Although psychiatric disorders such as autism spectrum disorders, schizophrenia and bipolar disorder affect a number of brain regions and produce a complex array of... (Review)
Review
Although psychiatric disorders such as autism spectrum disorders, schizophrenia and bipolar disorder affect a number of brain regions and produce a complex array of clinical symptoms, basic phenotypes likely exist at the level of single neurons and simple networks. Being highly heritable, it is hypothesized that these disorders are amenable to cell-based studies in vitro. Using induced pluripotent stem cell-derived neurons and/or induced neurons from fibroblasts, limitless numbers of live human neurons can now be generated from patients with a genetic background permissive to the disease state. We predict that cell-based studies will ultimately contribute to our understanding of the initiation, progression and treatment of these psychiatric disorders.
Topics: Animals; Fibroblasts; Humans; Induced Pluripotent Stem Cells; Mental Disorders; Models, Neurological; Neural Pathways; Neurons; Phenotype
PubMed: 22472874
DOI: 10.1038/mp.2012.20 -
The Journal of Neuroscience : the... Nov 2016Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult... (Review)
Review
Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases.
Topics: Animals; Brain; Chondroitin Sulfate Proteoglycans; Extracellular Matrix; Humans; Models, Neurological; Nerve Net; Neuronal Plasticity; Neurons
PubMed: 27911749
DOI: 10.1523/JNEUROSCI.2351-16.2016 -
Schizophrenia Bulletin Jan 2018Time is an essential feature in bipolar disorder (BP). Manic and depressed BP patients perceive the speed of time as either too fast or too slow. The present article... (Review)
Review
Time is an essential feature in bipolar disorder (BP). Manic and depressed BP patients perceive the speed of time as either too fast or too slow. The present article combines theoretical and empirical approaches to integrate phenomenological, psychological, and neuroscientific accounts of abnormal time perception in BP. Phenomenology distinguishes between perception of inner time, ie, self-time, and outer time, ie, world-time, that desynchronize or dissociate from each other in BP: inner time speed is abnormally slow (as in depression) or fast (as in mania) and, by taking on the role as default-mode function, impacts and modulates the perception of outer time speed in an opposite way, ie, as too fast in depression and too slow in mania. Complementing, psychological investigation show opposite results in time perception, ie, time estimation and reproduction, in manic and depressed BP. Neuronally, time speed can be indexed by neuronal variability, ie, SD. Our own empirical data show opposite changes in manic and depressed BP (and major depressive disorder [MDD]) with abnormal SD balance, ie, SD ratio, between somatomotor and sensory networks that can be associated with inner and outer time. Taken together, our combined theoretical-empirical approach demonstrates that desynchronization or dissociation between inner and outer time in BP can be traced to opposite neuronal variability patterns in somatomotor and sensory networks. This opens the door for individualized therapeutic "normalization" of neuronal variability pattern in somatomotor and sensory networks by stimulation with TMS and/or tDCS.
Topics: Bipolar Disorder; Humans; Nerve Net; Neurons; Sensorimotor Cortex; Time Perception
PubMed: 28525601
DOI: 10.1093/schbul/sbx050 -
Brain Pathology (Zurich, Switzerland) Jul 2017Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of... (Review)
Review
Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference "control" hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Neurodevelopmental Disorders; Neurons
PubMed: 28585386
DOI: 10.1111/bpa.12517 -
Cells Apr 2022Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized...
Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized compartments, such as axons and dendrites. Disruption of the Golgi apparatus (GA) secretory pathway in developing neurons alters axon/dendritic formation. Therefore, detailed knowledge of the mechanisms underlying vesicles exiting from the GA is crucial for understanding neuronal polarity. In this study, we analyzed the role of Brefeldin A-Ribosylated Substrate (CtBP1-S/BARS), a member of the C-terminal-binding protein family, in the regulation of neuronal morphological polarization and the exit of membrane proteins from the Trans Golgi Network. Here, we show that BARS is expressed during neuronal development in vitro and that RNAi suppression of BARS inhibits axonal and dendritic elongation in hippocampal neuronal cultures as well as largely perturbed neuronal migration and multipolar-to-bipolar transition during cortical development in situ. In addition, using plasma membrane (PM) proteins fused to GFP and engineered with reversible aggregation domains, we observed that expression of fission dominant-negative BARS delays the exit of dendritic and axonal membrane protein-containing carriers from the GA. Taken together, these data provide the first set of evidence suggesting a role for BARS in neuronal development by regulating post-Golgi membrane trafficking.
Topics: Axons; Golgi Apparatus; Membrane Proteins; Neurons; trans-Golgi Network
PubMed: 35455998
DOI: 10.3390/cells11081320 -
PloS One 2022The fork cell and von Economo neuron, which are found in the insular cortex and/or the anterior cingulate cortex, are defined by their unique morphologies. Their shapes...
The fork cell and von Economo neuron, which are found in the insular cortex and/or the anterior cingulate cortex, are defined by their unique morphologies. Their shapes are not pyramidal; the fork cell has two primary apical dendrites and the von Economo neurons are spindle-shaped (bipolar). Presence of such neurons are reported only in the higher animals, especially in human and great ape, indicating that they are specific for most evolved species. Although it is likely that these neurons are involved in higher brain function, lack of results with experimental animals makes further investigation difficult. We here ask whether equivalent neurons exist in the mouse insular cortex. In human, Fezf2 has been reported to be highly expressed in these morphologically distinctive neurons and thus, we examined the detailed morphology of Fezf2-positive neurons in the mouse brain. Although von Economo-like neurons were not identified, Fezf2-positive fork cell-like neurons with two characteristic apical dendrites, were discovered. Examination with electron microscope indicated that these neurons did not embrace capillaries, rather they held another cell. We here term such neurons as holding neurons. We further observed several molecules, including neuromedin B (NMB) and gastrin releasing peptide (GRP) that are known to be localized in the fork cells and/or von Economo cells in human, were localized in the mouse insular cortex. Based on these observations, it is likely that an equivalent of the fork cell is present in the mouse.
Topics: Animals; Cerebral Cortex; Gyrus Cinguli; Hominidae; Humans; Insular Cortex; Mice; Neurons
PubMed: 36067159
DOI: 10.1371/journal.pone.0274170 -
Journal of Pharmacological Sciences Aug 2019Since induced pluripotent stem cells (iPSCs) were generated from mice and humans by Professor Shinya Yamanaka et al. in 2006 and 2007, respectively, a variety of... (Review)
Review
Since induced pluripotent stem cells (iPSCs) were generated from mice and humans by Professor Shinya Yamanaka et al. in 2006 and 2007, respectively, a variety of human-derived cells have been generated, including myocardial, liver, retinal pigment epithelial, and neuronal cells. These iPSCs are now used not only in clinical research focusing on regeneration and transplantation in diverse medical fields, but also in molecular and cellular pathological studies. Importantly, by using human-derived iPSCs, it has become possible to conduct drug discovery research that more accurately models the pathology of human diseases. In research on psychiatric disorders, iPSC-related technologies, which have enabled the use of neuronal cells that carry the genetic information of the patients, will be important for elucidating not only the molecular and cellular etiology of psychiatric disorders but also the molecular mechanisms of drug action in these disorders. This review outlines the pharmacological research of psychiatric disorders that utilizes iPSC-related technologies.
Topics: Animals; Cell Culture Techniques; Drug Discovery; Humans; Induced Pluripotent Stem Cells; Mental Disorders; Neurons
PubMed: 31257060
DOI: 10.1016/j.jphs.2019.06.002