DOCSLIB.ORG

Dentate Granule Cells Form Novel Basal Dendrites in a Rat Model of Temporal Lobe Epilepsy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Neuroscience Vol. 86, No. 1, pp. 109–120, 1998 Copyright ? 1998 IBRO. Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved Pergamon PII: S0306-4522(98)00028-1 0306–4522/98 $19.00+0.00 DENTATE GRANULE CELLS FORM NOVEL BASAL DENDRITES IN A RAT MODEL OF TEMPORAL LOBE EPILEPSY I. SPIGELMAN,*†** X.-X. YAN,‡ A. OBENAUS,§ E. Y.-S. LEE,‡ C. G. WASTERLAIN†¶Q and C. E. RIBAK‡ *Section of Oral Biology, UCLA School of Dentistry, Los Angeles, CA 90095-1668, U.S.A. †UCLA Brain Research Institute, Los Angeles, California, U.S.A. ‡Department of Anatomy and Neurobiology, College of Medicine, UC, Irvine, CA 92697-1275, U.S.A. §University of Saskatchewan, Department of Medical Imaging, Saskatoon, Saskatchewan, Canada, S7N 0W8 ¶Epilepsy Research Laboratory, VA Medical Center (127), Sepulveda, CA 91343-2099, U.S.A. QDepartment of Neurology, UCLA School of Medicine, Los Angeles, California, U.S.A. Abstract––Mossy fibre sprouting and re-organization in the inner molecular layer of the dentate gyrus is a characteristic of many models of temporal lobe epilepsy including that induced by perforant-path stimulation. However, neuroplastic changes on the dendrites of granule cells have been less-well studied. Basal dendrites are a transient morphological feature of rodent granule cells during development. The goal of the present study was to examine whether granule cell basal dendrites are generated in rats with epilepsy induced by perforant-path stimulation. Adult Wistar rats were stimulated for 24 h at 2 Hz and with intermittent (1/min) trains (10 s duration) of single stimuli at 20 Hz (20 V, 0.1 ms) delivered 1/min via an electrode placed in the angular bundle. The brains of these experimental rats and age- and litter-matched control animals were processed for the rapid Golgi method. All rats with perforant-path stimulation displayed basal dendrites on many Golgi-impregnated granule cells. These basal dendrites mainly originated from their somata at the hilar side and then extended into the hilus. Quantitative analysis of more than 800 granule cells in the experimental and matched control brains showed that 6–15% (mean=8.7%) of the impregnated granule cells have spiny basal dendrites on the stimulated side, as well as the contralateral side (mean=3.1%, range=2.9–3.9%) of experimental rats, whereas no basal dendrites were observed in the dentate gyrus from control animals. The formation of basal dendrites appears to be an adaptive morphological change for granule cells in addition to the previously described mossy fibre sprouting, as well as dendritic and somatic spine formation observed in the dentate gyrus of animal and human epileptic brains. The presence of these dendrites in the subgranular region of the hilus suggests that they may be postsynaptic targets of the mossy fibre collaterals. ? 1998 IBRO. Published by Elsevier Science Ltd. Key words: perforant-path stimulation, basal dendrites, mossy fibre, sprouting, dentate gyrus, rat. The kainate and pilocarpine animal models of status ably similar to that seen in human patients with epilepticus (SE) produce widespread brain damage temporal lobe epilepsy.11,15,19 Spontaneous seizures and the delayed occurrence of limbic and general- have been tentatively explained either by the sprout- ized convulsions.8,9 Electrical stimulation of the ing and re-organization of recurrent excitatory perforant-path under urethane anaesthesia in adult connections1,9,10,49,50,53 or by the loss26 or deaffer- rats produces neuronal injury which is restricted to entation4,43 of inhibitory interneurons in the the hippocampus, has an excitotoxic appearance hippocampus. similar to that induced by kainic acid27,29,42,45 and The sprouting of granule cell axons, the mossy is associated with a loss of frequency-dependent, fibres, is commonly inferred in the dentate gyrus of paired-pulse inhibition in the dentate gyrus,43 as humans and experimental animals with epilepsy. In well as the progressive development of spontaneous the affected hippocampal formation, sprouted mossy recurrent seizures.41 The type of hippocampal dam- fibres form an aberrant band in the inner molecular age that is seen in animal models of SE is remark- layer of the dentate gyrus where they are in position to synapse with the proximal apical dendrites of granule cells.11,15,31,50,53 The elements postsynaptic **To whom correspondence should be addressed at the UCLA School of Dentistry. to the mossy fibres also display changes in temporal Abbreviations: ISI, interstimulus interval; PB, phosphate lobe epilepsy. For example, kainic acid treatment in buffer; PS, population spike; SE, status epilepticus. adult mice results in dendritic hypertrophy with 109 110 I. Spigelman et al. increased numbers of dendritic spines that is separation <1 mm for recording electrodes and <0.5 mm correlated with the sprouting of mossy fibres.52 In for the stimulating electrodes) were cemented to the skull by human studies, a greater density of dendritic spines dental acrylate. Final electrode depth (2.5–3.5 mm from cortical surface) was determined by maximizing the ampli- was noted in granule cells that exhibited aberrant tude of the characteristic potential recorded in the dentate mossy fibre collaterals as compared to cells without gyrus in response to ipsilateral perforant-path stimulation. such collaterals.16 In another study, longer and more Chromium non-coated wires (Consolidated Wire and branched granule cell apical dendrites were found in Associated Co.) were connected to the screws on the skull and used as ground electrodes. The skin was cleaned tissue from patients with mesial temporal lobe scler- with Povidine solution (Rugby Laboratories) and 10 mg of 54 osis as compared to those from a control group. penicillin (Sigma) was injected subcutaneously once per day Associated with the seizure-induced changes in for three days after surgery. granule cells are molecular responses that include increases in mRNAs encoding various neuro- In vivo recordings trophic substances.13 These latter changes are often Input/output (I/O) responses were obtained at 125, 200, reminiscent of developmental processes. 300, 500, 700, 1000, 2000 and 3000 ìA (0.1 Hz, 0.2 ms duration, biphasic stimulation). Interstimulus interval (ISI)- The granule cells of adult rats lack basal dendrites, dependent paired-pulse responses were studied at intervals although they are transiently expressed in rats during of 40 and 400 ms (0.1 Hz, 0.1 ms duration, monophasic postnatal development.37,38,40,57 This transient ex- stimulation). Population spike (PS) amplitudes were pression is also observed in several other species, measured from the average of five consecutive evoked including mouse, rabbit, guinea-pigs and cats (see potentials. PS amplitude was calculated as [(field potential at the beginning of PS)+(field potential at the end of Ref. 37). In contrast, basal dendrites are normal PS)]/2"(field potential at the peak of PS). In multiple PS features of granule cells in the developing and adult discharges, we used the first PS to measure PS amplitude. dentate gyrus of monkeys and humans.37 The bio- The inhibition score in paired-pulse examinations was logical significance of the developmental appearance calculated as [100"(PS amplitude of second pulse)/(PS amplitude of the 1st pulse) 100]. and subsequent attrition of granule cell basal den- # drites in rats is unknown. In a recent study, Franck Perforant-path stimulation et al.12 remarked on the apparent high spine density One to two weeks after surgery, rats were anaesthetized on the basal dendrites of granule cells in the brains with a loading dose of urethane (1000 mg/kg) via the tail of adult epileptic humans and suggested that their vein followed by a continuous infusion at 0.08 ml/min occurrence may provide an additional basis for recur- (1200 mg/kg). Once anaesthetized, rats were then stimulated rent excitation. However, no comparison was made for 22–24 h with single stimuli (20 V, 0.1 ms duration) at 2 Hz and with intermittent trains (10 s duration) of stimuli with the basal dendrites of age-matched humans and at 20 Hz delivered once per minute to the implanted stimu- therefore it is unclear whether these basal dendrites lating electrode. Paired-pulse stimulation was carried out are within the normal range observed in humans.37 before, during and at various times after stimulation. One The present study aimed to determine whether hour after the end of stimulation animals were injected with basal dendrites appear on granule cells of adult rats furosemide (10 mg/kg, i.m.). At various times rats were also injected subcutaneously with small volumes of dextrose as a consequence of SE induced by perforant-path solution. stimulation. Such an analysis conducted in epileptic rats would provide novel information about the Neurobiotin detection in granule cells formation of dendrites in the epileptic brain because, Intracellular recordings were made in hippocampal slices unlike humans, normal adult rats lack basal den- (400 ìm-thick) from stimulated and control rats according 56 drites. A rapid Golgi method was used to assess to previously described methods. Intracellular micro- the dendritic arbors of granule cells. A preliminary electrodes contained 1.5% Neurobiotin in 3 M potassium acetate (pH=7.25). Neurobiotin was injected into granule report of the data has been published in abstract cells (one cell/slice) using square-wave current pulses form.33 (1–3 nA, 100 ms, 3 Hz) for 15 to 25 min. Slices were im- mersed overnight in 4% paraformaldehyde in 0.1 M phos- EXPERIMENTAL PROCEDURES phate buffer (PB, pH=7.4). Slices were then incubated in 0.1 M PB containing 1% avidin–biotin–peroxidase complex Surgery (ABC; Vector) and 0.2% Triton X-100 at 4)C for 48 h. The Neurobiotin labelling was visualized in 0.05% diaminoben- Male adult Wistar rats (400–500 g; Simonsen Labs) were zidine and 0.005% H O in PB.
Recommended publications
  • Do Thin Spines Learn to Be Mushroom Spines That Remember? Jennifer Bourne and Kristen M Harris

    Do Thin Spines Learn to Be Mushroom Spines That Remember? Jennifer Bourne and Kristen M Harris

    CONEUR-488; NO OF PAGES 6 Do thin spines learn to be mushroom spines that remember? Jennifer Bourne and Kristen M Harris Dendritic spines are the primary site of excitatory input on most or whether they instead switch shapes depending on principal neurons. Long-lasting changes in synaptic activity are synaptic plasticity during learning. accompanied by alterations in spine shape, size and number. The responsiveness of thin spines to increases and decreases Maturation and stabilization of spines in synaptic activity has led to the suggestion that they are Spines tend to stabilize with maturation [5]; however, a ‘learning spines’, whereas the stability of mushroom spines small proportion continues to turnover in more mature suggests that they are ‘memory spines’. Synaptic brains [5–7]. The transient spines are thin spines that enhancement leads to an enlargement of thin spines into emerge and disappear over a few days, whereas mush- mushroom spines and the mobilization of subcellular resources room spines can persist for months [5,6]. Mushroom to potentiated synapses. Thin spines also concentrate spines have larger postsynaptic densities (PSDs) [1], biochemical signals such as Ca2+, providing the synaptic which anchor more AMPA glutamate receptors and make specificity required for learning. Determining the mechanisms these synapses functionally stronger [8–12]. Mushroom that regulate spine morphology is essential for understanding spines are more likely than thin spines to contain smooth the cellular changes that underlie learning and memory. endoplasmic reticulum, which can regulate Ca2+ locally [13], and spines that have larger synapses are also more Addresses Center for Learning and Memory, Department of Neurobiology, likely to contain polyribosomes for local protein synthesis University of Texas, Austin, TX 78712-0805, USA [14].
  • Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation

    Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation

    bioRxiv preprint doi: https://doi.org/10.1101/328534; this version posted August 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation Authors: Aman S. Aberra1, Angel V. Peterchev1,2,3,4, Warren M. Grill1,3,4,5,* 1 Dept. of Biomedical Engineering, School of Engineering, Duke University, NC 2 Dept. of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, NC 3 Dept. of Electrical and Computer Engineering, School of Engineering, Duke University, NC 4 Dept. of Neurosurgery, School of Medicine, Duke University, NC 5 Dept. of Neurobiology, School of Medicine, Duke University, NC * Corresponding Author: Warren M. Grill Keywords: neuron model, cortex, myelination, simulation, electric field, stimulation, axon bioRxiv preprint doi: https://doi.org/10.1101/328534; this version posted August 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 2 1. Abstract Objective. We implemented computational models of human and rat cortical neurons for simulating the neural response to cortical stimulation with electromagnetic fields. Approach. We adapted model neurons from the library of Blue Brain models to reflect biophysical and geometric properties of both adult rat and human cortical neurons and coupled the model neurons to exogenous electric fields (E-fields). The models included 3D reconstructed axonal and dendritic arbors, experimentally-validated electrophysiological behaviors, and multiple, morphological variants within cell types.
  • Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses

    Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses

    The Journal of Neuroscience, August 30, 2006 • 26(35):8881–8891 • 8881 Development/Plasticity/Repair Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses Michael Haber, Lei Zhou, and Keith K. Murai Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, H3G 1A4, Canada Accumulating evidence is redefining the importance of neuron–glial interactions at synapses in the CNS. Astrocytes form “tripartite” complexes with presynaptic and postsynaptic structures and regulate synaptic transmission and plasticity. Despite our understanding of the importance of neuron–glial relationships in physiological contexts, little is known about the structural interplay between astrocytes and synapses. In the past, this has been difficult to explore because studies have been hampered by the lack of a system that preserves complex neuron–glial relationships observed in the brain. Here we present a system that can be used to characterize the intricate relationshipbetweenastrocyticprocessesandsynapticstructuresinsituusingorganotypichippocampalslices,apreparationthatretains the three-dimensional architecture of astrocyte–synapse interactions. Using time-lapse confocal imaging, we demonstrate that astro- cytes can rapidly extend and retract fine processes to engage and disengage from motile postsynaptic dendritic spines. Surprisingly, astrocytic motility is, on average, higher than its dendritic spine
  • Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1 Jiyoung Park1,4*†, Athanasia Papoutsi3†, Ryan T

    Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1 Jiyoung Park1,4*†, Athanasia Papoutsi3†, Ryan T

    bioRxiv preprint doi: https://doi.org/10.1101/566588; this version posted March 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Contribution of Apical and Basal Dendrites of L2/3 Pyramidal Neurons to Orientation Encoding in Mouse V1 Jiyoung Park1,4*†, Athanasia Papoutsi3†, Ryan T. Ash2,4, Miguel A. Marin2, Panayiota Poirazi3* & Stelios M. Smirnakis4* 1Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 2Department of Neuroscience, Baylor College of Medicine, Houston, Texas 3Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology Hellas (FORTH), Vassilika Vouton, Heraklion, Crete, Greece 4Brigham and Women’s Hospital and Jamaica Plain VA Hospital, Harvard Medical School, Boston, MA †Equal contribution. * Correspondence: [email protected], [email protected], [email protected] Abstract: Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer- 2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2-3 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width.
  • Neuronal Organization of Olfactory Bulb Circuits

    Neuronal Organization of Olfactory Bulb Circuits

    REVIEW ARTICLE published: 03 September 2014 doi: 10.3389/fncir.2014.00098 Neuronal organization of olfactory bulb circuits Shin Nagayama 1*, Ryota Homma1 and Fumiaki Imamura 2 1 Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, TX, USA 2 Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, USA Edited by: Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is Benjamin R. Arenkiel, Baylor College dedicated to odor information processing.The olfactory bulb is divided into multiple layers, of Medicine, USA with different types of neurons found in each of the layers. Therefore, neurons in the Reviewed by: olfactory bulb have conventionally been categorized based on the layers in which their cell Kazushige Touhara, University of Tokyo, Japan bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the Veronica Egger, external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule Ludwig-Maximilians-Universität, cell layer. More recently, numerous studies have revealed the heterogeneous nature of each Germany Kathleen Quast, Baylor College of of these cell types, allowing them to be further divided into subclasses based on differences Medicine, USA in morphological, molecular, and electrophysiological properties. In addition, technical *Correspondence: developments and advances have resulted in an increasing number of studies regarding Shin Nagayama, Department of cell types other than the conventionally categorized ones described above, including short- Neurobiology and Anatomy, The axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the University of Texas Medical School at Houston, 6431 Fannin Street, olfactory bulb is now being acknowledged.
  • Action Potentials in Basal and Oblique Dendrites of Rat Neocortical Pyramidal Neurons Srdjan D

    Action Potentials in Basal and Oblique Dendrites of Rat Neocortical Pyramidal Neurons Srdjan D

    Physiology in Press; published online on May 9, 2003 as 10.1113/jphysiol.2002.033746 J Physiol (2003), xxx.x, pp. 000–000 DOI: 10.1113/jphysiol.2002.033746 © The Physiological Society 2003 www.jphysiol.org Action potentials in basal and oblique dendrites of rat neocortical pyramidal neurons Srdjan D. Antic Department of Cellular and Molecular Physiology, and Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA Basal and oblique dendrites comprise ~2/3 of the total excitable membrane in the mammalian cerebral cortex, yet they have never been probed with glass electrodes, and therefore their electrical properties and overall impact on synaptic processing are unknown. In the present study, fast multi- site voltage-sensitive dye imaging combined with somatic recording was used to provide a detailed description of the membrane potential transients in basal and oblique dendrites of pyramidal neurons during single and trains of action potentials (APs). The optical method allowed simultaneous measurements from several dendrites in the visual field up to 200 mm from the soma, thus providing a unique report on how an AP invades the entire dendritic tree. In contrast to apical dendrites, basal and oblique branches: (1) impose very little amplitude and time course modulation on backpropagating APs; (2) are strongly invaded by the somatic spike even when somatic firing rates reach 40 Hz (activity-independent backpropagation); and (3) do not exhibit signs of a ‘calcium shoulder’ on the falling phase of the AP. A compartmental model incorporating AP peak latencies and half-widths obtained from the apical, oblique and basal dendrites indicates that the specific intracellular resistance (Ri) is less than 100 V cm.
  • Coordinated Morphogenesis of Neurons and Glia

    Coordinated Morphogenesis of Neurons and Glia

    Available online at www.sciencedirect.com ScienceDirect Coordinated morphogenesis of neurons and glia Elizabeth R Lamkin and Maxwell G Heiman Glia adopt remarkable shapes that are tightly coordinated with The scope of the problem: highly dynamic and the morphologies of their neuronal partners. To achieve these localized morphological changes precise shapes, glia and neurons exhibit coordinated The intimate associations between glia and synapses morphological changes on the time scale of minutes and on exhibit highly dynamic morphological changes on the size scales ranging from nanometers to hundreds of microns. order of minutes [7–11]. Landmark studies using time- Here, we review recent studies that reveal the highly dynamic, lapse confocal imaging of rodent brain slices revealed that localized morphological changes of mammalian neuron–glia post-synaptic dendritic spines and astrocytic processes do contacts. We then explore the power of Drosophila and C. not change shape in perfect register, yet generally grow elegans models to study coordinated changes at defined or shrink together over time [7,9]. Remarkably, this neuron–glia contacts, highlighting the use of innovative genetic coordinated growth is achieved even though glia–spine and imaging tools to uncover the molecular mechanisms interactions undergo rapid structural changes, astrocytic responsible for coordinated morphogenesis of neurons processes tend to exhibit even greater motility than their and glia. dendritic spine counterparts, and the extent of glial coverage of spines varies [7]. Two recent, complementary studies provided evidence for a mechanism that may help to explain the coordinated growth of astrocytic processes and dendritic spines. Address Perez-Alvarez et al. and Bernardinelli et al.
  • Transient Hypoxemia Chronically Disrupts Maturation of Preterm Fetal Ovine Subplate Neuron Arborization and Activity

    Transient Hypoxemia Chronically Disrupts Maturation of Preterm Fetal Ovine Subplate Neuron Arborization and Activity

    11912 • The Journal of Neuroscience, December 6, 2017 • 37(49):11912–11929 Development/Plasticity/Repair Transient Hypoxemia Chronically Disrupts Maturation of Preterm Fetal Ovine Subplate Neuron Arborization and Activity XEvelyn McClendon,1 Daniel C. Shaver,1 Kiera Degener-O’Brien,1 Xi Gong,1 Thuan Nguyen,2 Anna Hoerder-Suabedissen,3 Zolta´n Molna´r,3 Claudia Mohr,4 XBen D. Richardson,4 David J. Rossi,4 and Stephen A. Back1,5 1Department of Pediatrics and 2Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon 97239, 3Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom OX1 3QX, 4Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164, and 5Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239 Preterm infants are at risk for a broad spectrum of neurobehavioral disabilities associated with diffuse disturbances in cortical growth and development. During brain development, subplate neurons (SPNs) are a largely transient population that serves a critical role to establish functional cortical circuits. By dynamically integrating into developing cortical circuits, they assist in consolidation of intra- cortical and extracortical circuits. Although SPNs reside in close proximity to cerebral white matter, which is particularly vulnerable to oxidative stress, the susceptibility of SPNs remains controversial. We determined SPN responses to two common insults to the preterm brain: hypoxia-ischemia and hypoxia. We used a preterm fetal sheep model using both sexes that reproduces the spectrum of human cerebral injury and abnormal cortical growth. Unlike oligodendrocyte progenitors, SPNs displayed pronounced resistance to early or delayed cell death from hypoxia or hypoxia-ischemia.
  • Autism Spectrum Disorder Susceptibility Gene TAOK2 Affects

    Autism Spectrum Disorder Susceptibility Gene TAOK2 Affects

    ART ic LE s Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex Froylan Calderon de Anda1,2, Ana Lucia Rosario1,2, Omer Durak1–3, Tracy Tran2,4,5, Johannes Gräff1,2, Konstantinos Meletis1–3,5, Damien Rei1,2, Takahiro Soda1,2, Ram Madabhushi1,2, David D Ginty2,4, Alex L Kolodkin2,4 & Li-Huei Tsai1–3 How neurons develop their morphology is an important question in neurobiology. Here we describe a new pathway that specifically affects the formation of basal dendrites and axonal projections in cortical pyramidal neurons. We report that thousand-and-one- amino acid 2 kinase (TAOK2), also known as TAO2, is essential for dendrite morphogenesis. TAOK2 downregulation impairs basal dendrite formation in vivo without affecting apical dendrites. Moreover, TAOK2 interacts with Neuropilin 1 (Nrp1), a receptor protein that binds the secreted guidance cue Semaphorin 3A (Sema3A). TAOK2 overexpression restores dendrite formation in cultured cortical neurons from Nrp1Sema− mice, which express Nrp1 receptors incapable of binding Sema3A. TAOK2 overexpression also ameliorates the basal dendrite impairment resulting from Nrp1 downregulation in vivo. Finally, Sema3A and TAOK2 modulate the formation of basal dendrites through the activation of the c-Jun N-terminal kinase (JNK). These results delineate a pathway whereby Sema3A and Nrp1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons. Pyramidal neurons are abundant in brain regions associated with through the activation of JNK11. TAOK2 is subjected to alternative complex cognitive functions, including the cortex, hippocampus and splicing to produce the TAOK2α (140 kDa) and TAOK2β (120 kDa) amygdala1.
  • Down-Regulation of Dendritic Spine and Glutamic Acid Decarboxylase 67 Expressions in the Reelin Haploinsufficient Heterozygous Reeler Mouse

    Down-Regulation of Dendritic Spine and Glutamic Acid Decarboxylase 67 Expressions in the Reelin Haploinsufficient Heterozygous Reeler Mouse

    Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse Wen Sheng Liu*, Christine Pesold*, Miguel A. Rodriguez*, Giovanni Carboni*, James Auta*, Pascal Lacor*, John Larson*, Brian G. Condie†, Alessandro Guidotti*, and Erminio Costa*‡ *Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois, Chicago, IL 60612; and †Institute of Molecular Medicine and Genetics, Departments of Medicine and Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912 Contributed by Erminio Costa, December 22, 2000 Heterozygous reeler mice (HRM) haploinsufficient for reelin ex- heterozygote reeler mice (HRM) and in heterozygote GAD67 Ϸ press 50% of the brain reelin content of wild-type mice, but are knockout mice (HG67M) and compared them to their respective phenotypically different from both wild-type mice and homozy- wild-type background mice (WTM). In the present study, we gous reeler mice. They exhibit, (i) a down-regulation of glutamic have also quantified the number of neurons immunopositive for acid decarboxylase 67 (GAD67)-positive neurons in some but not reelin in the motor area of the frontoparietal cortex (FPC) of every cortical layer of frontoparietal cortex (FPC), (ii) an increase of HRM, as well as the total number of neurons immunopositive for neuronal packing density and a decrease of cortical thickness NeuN and the number of glial cells stained by Nissl (13) because of neuropil hypoplasia, (iii) a decrease of dendritic spine expressed in each of the six layers of this cortical area. In WTM, expression density on basal and apical dendritic branches of motor HRM, and HG67M, we have also quantified the laminar expres- FPC layer III pyramidal neurons, and (iv) a similar decrease in sion of GAD67-immunopositive neurons and the dendritic spine dendritic spines expressed on the basal dendrite branches of CA1 density expressed by pyramidal neurons of layer III FPC and of pyramidal neurons of the hippocampus.
  • Contribution of Apical and Basal Dendrites to Orientation Encoding in Mouse V1 L2/3 Pyramidal Neurons

    Contribution of Apical and Basal Dendrites to Orientation Encoding in Mouse V1 L2/3 Pyramidal Neurons

    ARTICLE https://doi.org/10.1038/s41467-019-13029-0 OPEN Contribution of apical and basal dendrites to orientation encoding in mouse V1 L2/3 pyramidal neurons Jiyoung Park1,2,7*, Athanasia Papoutsi3,7, Ryan T. Ash1,4,5, Miguel A. Marin4,6, Panayiota Poirazi 3,8*& Stelios M. Smirnakis1,8* 1234567890():,; Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer-2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. Computational modeling corroborated our results and put limits on how orientation preferences among basal dendrites differ in order to reproduce the post-ablation data. In conclusion, neuronal orientation-tuning appears remarkably robust to loss of dendritic input. 1 Brigham and Women’s Hospital and Jamaica Plain VA Hospital, Harvard Medical School, Boston, MA, USA. 2 Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX, USA. 3 Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology Hellas (FORTH), Vassilika Vouton, HeraklionCrete, Greece.
  • Dendritic Size of Pyramidal Neurons Differs Among Mouse Cortical

    Dendritic Size of Pyramidal Neurons Differs Among Mouse Cortical

    Cerebral Cortex July 2006;16:990--1001 doi:10.1093/cercor/bhj041 Advance Access publication September 29, 2005 Dendritic Size of Pyramidal Neurons Differs Ruth Benavides-Piccione1,2, Farid Hamzei-Sichani2, Inmaculada Ballesteros-Ya´n˜ez1, Javier DeFelipe1 and Rafael Yuste1,2 among Mouse Cortical Regions 1Instituto Cajal, Madrid, Spain and 2HHMI, Department of Biological Sciences, Columbia University, New York, USA Downloaded from https://academic.oup.com/cercor/article-abstract/16/7/990/425668 by University of Massachusetts Medical School user on 19 February 2019 Neocortical circuits share anatomical and physiological similarities a series of basic circuit diagrams based on anatomical and among different species and cortical areas. Because of this, electrophysiological data (Douglas et al., 1989, 1995; Douglas a ‘canonical’ cortical microcircuit could form the functional unit and Martin, 1991, 1998, 2004). According to their hypothesis, of the neocortex and perform the same basic computation on the common transfer function that the neocortex performs on different types of inputs. However, variations in pyramidal cell inputs could be related to the amplification of the signal structure between different primate cortical areas exist, indicating (Douglas et al., 1989) or a ‘soft’ winner-take-all algorithm that different cortical areas could be built out of different neuronal (Douglas and Martin, 2004). These ideas agree with the re- cell types. In the present study, we have investigated the dendritic current excitation present in cortical tissue which could then architecture of 90 layer II/III pyramidal neurons located in different exert a top-down amplification and selection on thalamic inputs cortical regions along a rostrocaudal axis in the mouse neocortex, (Douglas et al., 1995).