Information

Related Research Units

Intellectual and Developmental Disabilities Research Center Research
Neurology Research
F.M. Kirby Neurobiology Center

Research Overview

Neurons acquire multiple functional properties through experience-dependent development during specific times in early postnatal life called “critical periods”. In recent years we have achieved the first direct control over critical period timing by manipulating a specific subset of local inhibitory circuits in the visual cortex. Our research focuses on the mechanisms underlying these fundamental processes and how they may be altered in neurodevelopmental disorders. To this end, we combine molecular techniques with electrophysiological and behavioral analysis of systems level phenomena in vivo.

Currently we are studying experience-dependent brain development in mouse models of autism spectrum disorders (ASDs). We are particularly focused on Rett Syndrome, a leading cause of intellectual disability with autistic features. We are developing new strategies to restore cortical function and critical period timing by targeting Excitatory/Inhibitory circuits as a possible therapeutic intervention. 

Research Background

Dr. Fagiolini received her M.S. in Biological Sciences from University of Pisa, Italy and her Ph.D. in Neurobiology from Scuola Normale Superiore, Italy. After completing a postdoctoral fellowship in Physiology at the University of California, San Francisco under the mentorship of Dr. Michael P. Stryker, she joined the Laboratory for Neuronal Circuit Development at the Brain Science Institute in Japan. There she began a productive collaboration with Dr. Takao K. Hensch.

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Meet Michela Fagiolini, PhD

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Watch Dr. Fagiolini meet with a family affected by Rett syndrome.

Publications

  1. Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids. bioRxiv. 2024 Aug 10. View Abstract
  2. CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility. Mol Psychiatry. 2024 Jun; 29(6):1698-1709. View Abstract
  3. Correction: Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes. Mol Psychiatry. 2022 Sep; 27(9):3920-3921. View Abstract
  4. Dynamical Characteristics of Wild-Type Mouse Spontaneous Pupillary Fluctuations. Annu Int Conf IEEE Eng Med Biol Soc. 2021 11; 2021:853-856. View Abstract
  5. Phenotypic characterization of Cdkl5-knockdown neurons establishes elongated cilia as a functional assay for CDKL5 Deficiency Disorder. Neurosci Res. 2022 Mar; 176:73-78. View Abstract
  6. Visual Dysfunction after Repetitive Mild Traumatic Brain Injury in a Mouse Model and Ramifications on Behavioral Metrics. J Neurotrauma. 2021 10 15; 38(20):2881-2895. View Abstract
  7. Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes. Mol Psychiatry. 2021 12; 26(12):7610-7620. View Abstract
  8. Animal Models of Neurodevelopmental Disorders. Neuroscience. 2020 10 01; 445:1-2. View Abstract
  9. The Stage of the Estrus Cycle Is Critical for Interpretation of Female Mouse Social Interaction Behavior. Front Behav Neurosci. 2020; 14:113. View Abstract
  10. Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders. Neuroscience. 2020 10 01; 445:190-206. View Abstract
  11. Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2. Cereb Cortex. 2020 01 10; 30(1):256-268. View Abstract
  12. Behavioral analyses of animal models of intellectual and developmental disabilities. Neurobiol Learn Mem. 2019 11; 165:107087. View Abstract
  13. Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients. Proc Natl Acad Sci U S A. 2020 09 22; 117(38):23298-23303. View Abstract
  14. MeCP2: an epigenetic regulator of critical periods. Curr Opin Neurobiol. 2019 12; 59:95-101. View Abstract
  15. A Diet With Docosahexaenoic and Arachidonic Acids as the Sole Source of Polyunsaturated Fatty Acids Is Sufficient to Support Visual, Cognitive, Motor, and Social Development in Mice. Front Neurosci. 2019; 13:72. View Abstract
  16. NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity. Mol Psychiatry. 2019 06; 24(6):828-838. View Abstract
  17. Transparent, Flexible, Penetrating Microelectrode Arrays with Capabilities of Single-Unit Electrophysiology. Adv Biosyst. 2019 03; 3(3):e1800276. View Abstract
  18. Transparent arrays of bilayer-nanomesh microelectrodes for simultaneous electrophysiology and two-photon imaging in the brain. Sci Adv. 2018 09; 4(9):eaat0626. View Abstract
  19. Rigor and reproducibility in rodent behavioral research. Neurobiol Learn Mem. 2019 11; 165:106780. View Abstract
  20. FANTOM5 CAGE profiles of human and mouse samples. Sci Data. 2017 08 29; 4:170112. View Abstract
  21. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017 07 06; 8:16077. View Abstract
  22. Cortical Feedback Regulates Feedforward Retinogeniculate Refinement. Neuron. 2016 Sep 07; 91(5):1021-1033. View Abstract
  23. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons. Nature. 2016 Mar 17; 531(7594):371-5. View Abstract
  24. MPX-004 and MPX-007: New Pharmacological Tools to Study the Physiology of NMDA Receptors Containing the GluN2A Subunit. PLoS One. 2016; 11(2):e0148129. View Abstract
  25. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-232. View Abstract
  26. Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors. Epigenetics Chromatin. 2015; 8:55. View Abstract
  27. Visual evoked potentials detect cortical processing deficits in Rett syndrome. Ann Neurol. 2015 Nov; 78(5):775-86. View Abstract
  28. Chronic Administration of the N-Methyl-D-Aspartate Receptor Antagonist Ketamine Improves Rett Syndrome Phenotype. Biol Psychiatry. 2016 May 01; 79(9):755-764. View Abstract
  29. Cell-Specific Regulation of N-Methyl-D-Aspartate Receptor Maturation by Mecp2 in Cortical Circuits. Biol Psychiatry. 2016 May 01; 79(9):746-754. View Abstract
  30. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science. 2015 Feb 27; 347(6225):1010-4. View Abstract
  31. CAGE-defined promoter regions of the genes implicated in Rett Syndrome. BMC Genomics. 2014 Dec 24; 15:1177. View Abstract
  32. Sensory integration in mouse insular cortex reflects GABA circuit maturation. Neuron. 2014 Aug 20; 83(4):894-905. View Abstract
  33. A promoter-level mammalian expression atlas. Nature. 2014 Mar 27; 507(7493):462-70. View Abstract
  34. An atlas of active enhancers across human cell types and tissues. Nature. 2014 Mar 27; 507(7493):455-461. View Abstract
  35. Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15. J Neurosci. 2014 Mar 05; 34(10):3517-22. View Abstract
  36. Visual acuity development and plasticity in the absence of sensory experience. J Neurosci. 2013 Nov 06; 33(45):17789-96. View Abstract
  37. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2. Neuron. 2012 Dec 20; 76(6):1078-90. View Abstract
  38. Trehalose-enhanced isolation of neuronal sub-types from adult mouse brain. Biotechniques. 2012 Jun; 52(6):381-5. View Abstract
  39. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc Natl Acad Sci U S A. 2012 Jun 05; 109(23):9149-54. View Abstract
  40. Autism: a "critical period" disorder? Neural Plast. 2011; 2011:921680. View Abstract
  41. Common circuit defect of excitatory-inhibitory balance in mouse models of autism. J Neurodev Disord. 2009 Jun; 1(2):172-81. View Abstract
  42. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol. 2009 Apr; 19(2):207-12. View Abstract
  43. Observation of pulsed gamma-rays above 25 GeV from the Crab pulsar with MAGIC. Science. 2008 Nov 21; 322(5905):1221-4. View Abstract
  44. A resource for transcriptomic analysis in the mouse brain. PLoS One. 2008 Aug 20; 3(8):e3012. View Abstract
  45. Very-high-energy gamma rays from a distant quasar: how transparent is the universe? Science. 2008 Jun 27; 320(5884):1752-4. View Abstract
  46. Optimization of somatic inhibition at critical period onset in mouse visual cortex. Neuron. 2007 Mar 15; 53(6):805-12. View Abstract
  47. Developmental plasticity of inhibitory circuitry. J Neurosci. 2006 Oct 11; 26(41):10358-61. View Abstract
  48. Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303. Science. 2006 Jun 23; 312(5781):1771-3. View Abstract
  49. The transcriptional landscape of the mammalian genome. Science. 2005 Sep 02; 309(5740):1559-63. View Abstract
  50. Excitatory-inhibitory balance and critical period plasticity in developing visual cortex. Prog Brain Res. 2005; 147:115-24. View Abstract
  51. Specific GABAA circuits for visual cortical plasticity. Science. 2004 Mar 12; 303(5664):1681-3. View Abstract
  52. Subtraction of cap-trapped full-length cDNA libraries to select rare transcripts. Biotechniques. 2003 Sep; 35(3):510-6, 518. View Abstract
  53. Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci. 2003 Jul 30; 23(17):6695-702. View Abstract
  54. Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. Genome Res. 2003 Jun; 13(6B):1273-89. View Abstract
  55. Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling. Proc Natl Acad Sci U S A. 2003 Mar 04; 100(5):2854-9. View Abstract
  56. Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development. Neuroscience. 2001; 108(4):569-85. View Abstract
  57. Inhibitory threshold for critical-period activation in primary visual cortex. Nature. 2000 Mar 09; 404(6774):183-6. View Abstract
  58. Role of neurotrophins in the development and plasticity of the visual system: experiments on dark rearing. Int J Psychophysiol. 2000 Mar; 35(2-3):189-96. View Abstract
  59. Anatomical correlates of functional plasticity in mouse visual cortex. J Neurosci. 1999 Jun 01; 19(11):4388-406. View Abstract
  60. Local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science. 1998 Nov 20; 282(5393):1504-8. View Abstract
  61. Axonal transport blockade in the neonatal rat optic nerve induces limited retinal ganglion cell death. J Neurosci. 1997 Sep 15; 17(18):7045-52. View Abstract
  62. Temporal aspects of contrast visual evoked potentials in the pigmented rat: effect of dark rearing. Vision Res. 1997 Feb; 37(4):389-95. View Abstract
  63. Transplant of Schwann cells allows normal development of the visual cortex of dark-reared rats. Eur J Neurosci. 1997 Jan; 9(1):102-12. View Abstract
  64. Schwann cells transplanted in the lateral ventricles prevent the functional and anatomical effects of monocular deprivation in the rat. Proc Natl Acad Sci U S A. 1994 Mar 29; 91(7):2572-6. View Abstract
  65. Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation. Vision Res. 1994 Mar; 34(6):709-20. View Abstract
  66. Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system. Proc Natl Acad Sci U S A. 1994 Jan 18; 91(2):684-8. View Abstract

Contact Michela Fagiolini

Phone: 617-919-2419
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