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Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 2/2009

Open Access 01-06-2009 | Article

Common circuit defect of excitatory-inhibitory balance in mouse models of autism

Authors: Nadine Gogolla, Jocelyn J. LeBlanc, Kathleen B. Quast, Thomas C. Südhof, Michela Fagiolini, Takao K. Hensch

Published in: Journal of Neurodevelopmental Disorders | Issue 2/2009

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Abstract

One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit refinement (Hensch Nat Rev Neurosci 6:877–888, 1), are disrupted across heterogeneous ASD mouse models. We performed a meta-analysis of PV expression in previously published ASD mouse models and analyzed two additional models, reflecting an embryonic chemical insult (prenatal valproate, VPA) or single-gene mutation identified in human patients (Neuroligin-3, NL-3 R451C). PV-cells were reduced in the neocortex across multiple ASD mouse models. In striking contrast to controls, both VPA and NL-3 mouse models exhibited an asymmetric PV-cell reduction across hemispheres in parietal and occipital cortices (but not the underlying area CA1). ASD mouse models may share a PV-circuit disruption, providing new insight into circuit development and potential prevention by treatment of autism.
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Literature
1.
Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005;6:877–88.CrossRefPubMed
2.
Zoghbi HY. Postnatal neurodevelopment disorders: meeting at the synapse? Science. 2003;302:826–30.CrossRefPubMed
3.
4.
Rubenstein J, Merzenich M. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain, and Behavior. 2003;2(5):255–67.CrossRefPubMed
5.
6.
7.
Fagiolini M, Hensch TK. Inhibitory threshold for critical-period activation in primary visual cortex. Nature. 2000;404:183–6.CrossRefPubMed
8.
Iwai Y, Fagiolini M, Obata K, Hensch TK. Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci. 2003;23:6695–6702.PubMed
9.
Fagiolini M, Fritschy JM, Low K, Mohler H, Rudolph U, Hensch TK. Specific GABAA circuits for visual cortical plasticity. Science. 2004;303:1681–83.CrossRefPubMed
10.
Katagiri H, Fagiolini M, Hensch TK. Optimization of somatic inhibition at critical period onset in mouse visual cortex. Neuron. 2007;53:805–12.CrossRefPubMed
11.
Sugiyama S, et al. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell. 2008;134(3):508–20.CrossRefPubMed
12.
Gonchar Y, Wang Q, Burkhalter A. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining. Front Neuroanat. 2007;1:3.PubMedCentralPubMed
13.
Butt SJ, Fuccillo M, Nery S, Noctor S, Kriegstein A, Corbin JG, et al. The temporal and spatial origins of cortical interneurons predict their physiological subtype. Neuron. 2005;48:591–604.CrossRefPubMed
14.
Del Rio J, et al. The development of parvalbumin-immunoreactivity in the neocortex of the mouse. Brain Research Development. 1994;81(2):247–59.CrossRef
15.
Hartig W, Derouiche A, Welt K, Brauer K, Grosche J, Mader M, et al. Cortical neurons immunoreactive for the potassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as a buffering system for cations. Brain Res. 1999;842:15–29.CrossRefPubMed
16.
Galtrey CM, Fawcett JW. The role of chondroitin sulfate proteoglycans in regeneration and plasticity in the central nervous system. Brain Res Rev. 2007;54:1–18.CrossRefPubMed
17.
Pizzorusso T, et al. Reactivation of ocular dominance plasticity in the adult visual cortex. Science. 2002;298(5596):1248–51.CrossRefPubMed
18.
Losh M, Sullivan PF, Trembath D, Piven JJ. Current developments in the genetics of autism: from phenome to genome. Neuropathol Exp Neurol. 2008;67:829–37.CrossRef
19.
Christianson AL, Chesler N, Kromberg JG. Fetal valproate syndrome: clinical and neuro-developmental features in two sibling pairs. Dev Med Child Neurol. 1994;36:361–9.CrossRefPubMed
20.
Hyman S, Arndt TL, Rodier PM. Enviromental agents and autism: once and futi\ure associations. International Review of Research in Mental Retardation. 2006;30:171–94.CrossRef
21.
Miyazaki K, Narita N, Narita N. Maternal administration of thalidomide of valproic acid causes abnormal serotonergic neurons in the offspring: implication for pathogenesis of autism. International Jornal of Developmental Neuroscience. 2005;23:287–97.CrossRef
22.
Rinaldi T, et al. Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. PNAS. 2007;104(33):13501–6.CrossRefPubMedCentralPubMed
23.
Markram K, Rinaldi T, La Mendola D, Sandi C, Markram H. Abnormal fear conditioning and amygdala processing in an animal model of autism. Neuropsychopharmacology. 2008;33(4):901–12.CrossRefPubMed
24.
Wagner G, et al. A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate. Journal of Developmental Disorders. 2006;36:779–93.CrossRef
25.
Yochum C, et al. VPA-induced apoptosis and behavioral deficits in neonatal mice. Brain Res. 2008;1203:126–32.CrossRefPubMed
26.
Nadler J, et al. Automated apparatus for quantitation of social approach behaviors in mice. Genes, Brain, and Behavior. 2004;3(5):303–14.CrossRefPubMed
27.
28.
29.
30.
Vreugdenhil M, et al. Parvalbumin-deficiency facilitates repetitive IPSCs and gamma oscillations in the hippocampus. J Neurophysiol. 2003;89(3):1414–22.CrossRefPubMed
31.
Bartos M, Vida I, Jonas P. Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci. 2007;8:45–56.CrossRefPubMed
32.
33.
34.
Sarihi A, Jiang B, Komaki A, Sohya K, Yanagawa Y, Tsumoto T. Metabotropic glutamate receptor type 5-dependent long-term potentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex. J Neurosci. 2008;28:1224–35.CrossRefPubMed
35.
Singer W. Synchronization of cortical activity and its putative role in information processing and learning. Annu Rev Physiol. 1993;55:349–74.CrossRefPubMed
36.
Lisman JE, Idiart MA. Storage of 7 +/− 2 short-term memories in oscillatory subcycles. Science. 1995;267:1512–15.CrossRefPubMed
37.
Murthy VN, Fetz EE. Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys. Proc Natl Acad Sci USA. 1992;89:5670–74.CrossRefPubMedCentralPubMed
38.
Fries P, Reynolds JH, Rorie AE, Desimone R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science. 2001;291:1560–63.CrossRefPubMed
39.
Nase G, Singer W, Monyer H, Engel AK. Features of neuronal synchrony in mouse visual cortex. J Neurophysiol. 2003;90:1115–23.CrossRefPubMed
40.
MacDonald KD, Barth DS. High frequency (gamma-band) oscillating potentials in rat somatosensory and auditory cortex. Brain Res. 1995;694:1–12.CrossRefPubMed
41.
Ribary U. Dynamics of thalamo-cortical network oscillations and human perception. Prog Brain Res. 2005;150:127–42.CrossRefPubMed
42.
Mann EO, Paulsen O. Mechanisms underlying gamma (‘40 Hz’) network oscillations in the hippocampus—a mini-review. Prog Biophys Mol Biol. 2005;87:67–76.CrossRefPubMed
43.
Buhl EH, Tamas G, Fisahn A. Cholinergic activation and tonic excitation induce persistent gamma oscillations in mouse somatosensory cortex in vitro. J Physiol. 1998;513(Pt 1):117–26.CrossRefPubMedCentralPubMed
44.
Cunningham MO, Whittington MA, Bibbig A, Roopun A, LeBeau FE, Vogt A, et al. A role for fast rhythmic bursting neurons in cortical gamma oscillations in vitro. Proc Natl Acad Sci USA. 2004;101:7152–57.CrossRefPubMedCentralPubMed
45.
Metherate R, Cruikshank SJ. Thalamocortical inputs trigger a propagating envelope of gamma-band activity in auditory cortex in vitro. Exp Brain Res. 1999;126:160–74.CrossRefPubMed
46.
Fuchs EC, Zivkovic AR, Cunningham MO, Middleton S, Lebeau FE, Bannerman DM, et al. Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior. Neuron. 2007;53:591–604.CrossRefPubMed
47.
Wulff P, Ponomarenko AA, Bartos M, Korotkova TM, Fuchs EC, Bähner F, et al. Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons. Proc Natl Acad Sci USA. 2009;106:3561–6.CrossRefPubMedCentralPubMed
48.
Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 2009; in press.
49.
Sohal VS, Zhang F, Yizhar O, Deisseroth K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 2009; in press.
50.
Grabert J, Wahle P. Visual experience regulates Kv3.1b and Kv3.2 expression in developing rat visual cortex. Neuroscience. 2009;158:654–64.CrossRefPubMed
51.
Kawaguchi Y, Kubota Y. Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28k-immunoreactive neurons in layer V of rat frontal cortex. J Neurophysiol. 1993;70:387–96.PubMed
52.
Kawaguchi Y. Physiological subgroups of nonpyramidal cells with specific morphological characteristics in layer II/III of rat frontal cortex. J Neurosci. 1995;15:2638–55.PubMed
53.
Plotkin JL, Wu N, Chesselet MF, Levine MS. Functional and molecular development of striatal fast-spiking GABAergic interneurons and their cortical inputs. Eur J Neurosci. 2005;22:1097–108.CrossRefPubMed
54.
Doischer D, Hosp JA, Yanagawa Y, Obata K, Jonas P, Vida I, et al. Postnatal differentiation of basket cells from slow to fast signaling devices. J Neurosci. 2008;28:12956–68.CrossRefPubMed
55.
Joho RH, Ho CS, Marks GA. Increased gamma- and decreased delta-oscillations in a mouse deficient for a potassium channel expressed in fast-spiking interneurons. J Neurophysiol. 1999;82:1855–64.PubMed
56.
Traub RD, Bibbig A. A model of high-frequency ripples in the hippocampus based on synaptic coupling plus axon-axon gap junctions between pyramidal neurons. J Neurosci. 2000;20:2086–93.PubMed
57.
Traub RD, Kopell N, Bibbig A, Buhl EH, LeBeau FE, Whittington MA. Gap junctions between interneuron dendrites can enhance synchrony of gamma oscillations in distributed networks. J Neurosci. 2001;21:9478–86.PubMed
58.
Hormuzdi SG, Pais I, LeBeau FE, Towers SK, Rozov A, Buhl EH, et al. Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron. 2001;31:487–95.CrossRefPubMed
59.
Buhl DL, Harris KD, Hormuzdi SG, Monyer H, Buzsaki G. Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in vivo. J Neurosci. 2003;23:1013–18.PubMed
60.
Csicsvari J, Jamieson B, Wise KD, Buzsaki G. Mechanisms of gamma oscillations in the hippocampus of the behaving rat. Neuron. 2003;37:311–22.CrossRefPubMed
61.
Hajos N, Palhalmi J, Mann EO, Nemeth B, Paulsen O, Freund TF. Spike timing of distinct types of GABAergic interneuron during hippocampal gamma oscillations in vitro. J Neurosci. 2004;24:9127–37.CrossRefPubMed
62.
Cruikshank SJ, Lewis TJ, Connors BW. Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex. Nat Neurosci. 2007;10:462–8.PubMed
63.
Galarreta M, Hestrin S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science. 2001;292:2295–9.CrossRefPubMed
64.
Uhlhaas P, Singer W. What do disturbances in neural synchrony tell us about autism? Biol Psychiatry. 2006;62:190–1.CrossRef
65.
Behrendt RP. Hallucinations: synchronisation of thalamocortical gamma oscillations under-constrained by sensory input. Conscious Cogn. 2003;12:413–51.CrossRefPubMed
66.
Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005;6:312–24.CrossRefPubMed
67.
Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, et al. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci. 2008;31:234–42.CrossRefPubMedCentralPubMed
68.
Gonzalez-Burgos G, Lewis DA. GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull. 2008;34:944–61.CrossRefPubMedCentralPubMed
69.
Lodge DJ, Behrens MM, Grace AA. A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci. 2009;29:2344–54.CrossRefPubMedCentralPubMed
70.
Wilson TW, Rojas DC, Reite ML, Teale PD, Rogers SJ. Children and adolescents with autism exhibit reduced MEG steady-state gamma responses. Biol Psychiatry. 2007;62:192–7.CrossRefPubMedCentralPubMed
71.
Brown C, Gruber T, Boucher J, Rippon G, Brock J. Gamma abnormalities during perception of illusory figures in autism. Cortex. 2005;41:364–76.CrossRefPubMed
72.
Grice S, et al. Disordered visual processing and oscillatory brain activity in autism and Williams syndrome. Neuroreport. 2001;12:2697–700.CrossRefPubMed
73.
Mitchell JF, Sundberg KA, Reynolds JH. Differential attention-dependent response modulation across cell classes in macaque visual area V4. Neuron. 2007;55:131–41.CrossRefPubMed
74.
Rippon G, Brock J, Brown C, Boucher J. Disordered connectivity in the autistic brain: challenges for the “new psychophysiology”. Int J Psychophysiol. 2007;63:164–72.CrossRefPubMed
75.
Welsh JP, Ahn ES, Placantonakis DG. Is autism due to brain desynchronization? Int J Dev Neurosci. 2005;23:253–63.CrossRefPubMed
76.
Just MA, Cherkassky VL, Keller TA, Minshew NJ. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain. 2004;127:1811–21.CrossRefPubMed
77.
Casanova MF, Buxhoeveden D, Gomez J. Disruption in the inhibitory architecture of the cell minicolumn: implications for autism. Neuroscientist. 2003;9:496–507.CrossRefPubMed
78.
79.
80.
Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol. 2007;17:103–11.CrossRefPubMed
81.
Courchesne E, Pierce K. Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol. 2005;15:225–30.CrossRefPubMed
82.
Brock J, Brown CC, Boucher J, Rippon G. The temporal binding deficit hypothesis of autism. Dev Psychopathol. 2002;14:209–24.CrossRefPubMed
83.
Muller RA, Kleinhans N, Kemmotsu N, Pierce K, Courchesne E. Abnormal variability and distribution of functional maps in autism: an FMRI study of visuomotor learning. Am J Psychiatry. 2003;160:1847–62.CrossRefPubMed
84.
Koshino H, Carpenter PA, Minshew NJ, Cherkassky VL, Keller TA, Just MA. Functional connectivity in an fMRI working memory task in high-functioning autism. Neuroimage. 2005;24:810–21.CrossRefPubMed
85.
Koshino H, Kana RK, Keller TA, Cherkassky VL, Minshew NJ, Just MA. fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas. Cereb Cortex. 2008;18:289–300.CrossRefPubMedCentralPubMed
86.
87.
McFarlane H, et al. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain, and Behavior. 2008;7:152–63.CrossRefPubMed
88.
Herrera CG, Hung J, Zhang Y, Kertesz AC, Espina FJ, Colicos MA. Altered synchrony and connectivity in neuronal networks expressing an autism-related mutation of neuroligin 3. Neuroscience 2009; in press.
89.
Zhang L, He J, Jugloff DG, Eubanks JH. The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability. Hippocampus. 2008;18:294–309.CrossRefPubMed
90.
Gibson JR, Bartley AF, Hays SA, Huber KM. Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J Neurophysiol. 2008;100:2615–26.CrossRefPubMedCentralPubMed
91.
Kuhlman SJ, Huang ZJ. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression. PLoS ONE. 2008;3:e2005.CrossRefPubMedCentralPubMed
92.
Polleux F, Lauder J. Toward a developmental neurobiology of autism. Mental Retard Dev Dis. 2004;10:303–17.CrossRef
93.
Levitt P, et al. Regulation of neocortical interneuron development and the implications for neurodevelopmental disorders. Trends Neurosci. 2004;27:400–6.CrossRefPubMed
94.
Selby L, et al. Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein. Neurosci Letters. 2007;412:227–32.CrossRef
95.
Fukuda T, et al. Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005;64:537–44.PubMed
96.
Sadakata T, et al. Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest. 2007;117:931–42.CrossRefPubMedCentralPubMed
97.
Powell E, et al. Genetic disruption of cortical interneuron development causes region and GABA cell type specific deficits, epilepsy, and behavioral dysfunction. J Neurosci. 2003;23:622–31.PubMed
98.
Meyer U, et al. Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice. Brain, Behav Immun. 2007;22:469–86.CrossRef
99.
Gant JC, et al. Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: Implications for autism and epilepsy. Epilepsia 2009; in press.
100.
Tripathi P, et al. Increased susceptibility to kainic acid-induced seizures in Engrailed-2 knockout mice. Neuroscience. 2009;159:842–9.CrossRefPubMed
Metadata
Title
Common circuit defect of excitatory-inhibitory balance in mouse models of autism
Authors
Nadine Gogolla
Jocelyn J. LeBlanc
Kathleen B. Quast
Thomas C. Südhof
Michela Fagiolini
Takao K. Hensch
Publication date
01-06-2009
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 2/2009
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1007/s11689-009-9023-x

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