Convergent synaptic and circuit substrates underlying autism genetic risks

Abstract

There has been a surge of diagnosis of autism spectrum disorders (ASD) over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.

Key words： autism spectrum disorders; development; risk genes; synapse; circuits; behavior; neurodevelopmental disorders

Acknowledgements

The authors would like to thank Prof. G. Victor Rajamanickam, former Dean of Tamil University, Tanjore, and SASTRA University for his kind assistance during the course of sample collection. The authors also thank Mrs. J. Elizabeth Christina, Assistant Professor, Scott Christian College, Nagercoil, Tamil Nadu, India, who helped in the proof correction of the manuscript. Finally, the authors thank Dr. Joseph Johnson, Director of Unity Foundation, and Tirunelveli, who helped to mould the manuscript in a spectacular way.

References

1 AltaffK, SugumaranJ M, NaveedS (2005). Impact of tsunami on meiofauna of Marina beach, Chennai, India. Current Sci, 89(10): 1646

2 AriasC R, AznarR, PujalteM J, GarayE (1998). A comparison of strategies for the detection and recovery of Vibrio vulnificus from marine samples of the western Mediterranean coast. Syst Appl Microbiol, 21(1): 128–134

PMID

3 AzamF, FenchelT, FieldJ G, GrayJ S, Meyer-ReilL A, ThingstadF (1983). The ecological role of water- column microbes in the sea. Mar Ecol Prog Ser, 10: 257–263

4 BlackeP A, WeanerR E, HoillisD G (1981). Diseases of humans (other than cholera) caused by Vibrio. Annu Rev Microbiol, 34(1): 341–347

5 BoeschD F, DiazR J, VirnsteinR W (1976a). Effects of tropical storm Agnes on soft-bottom communities of the James and York estuaries and the lower Chesapeake Bay. Chesap Sci, 17(4): 246–259

6 BourgeoisJ, HansenT A, WibergP L, KaufmannE G (1988). A tsunami deposit at the Cretaceous-Tertiary Boundary in Texas. Science241:567–570

7 BryantE (2001). Tsunami. The underrated hazard. Cambridge University Press, Cambridge

8 BryantE, YoungR, PriceD (1996). Tsunami as a major control of coastal evolution, southeastern Australia. J Coast Res, 12: 831–840

9 CarlsonG F, WoodardF E, WentworthD F, SproulO J (1968). Virus inactivation on clay particles in natural waters, Journal of the Water Pollution Control Federation. 40:98–106

10 CheungW H S, ChangK C K, HungR P S, KleevensJ W L (1990). Health effects of beach water pollution in Hong Kong. Epidemiol Infect, 105(1): 139–162

PMID

11 CitaM B, AloisiG (2000). Deep-sea tsunami deposits triggered by the explosion of Santorini (3500 y BP), eastern Mediterranean. Sediment Geol, 135(1–4): 181–203

12 DasS, LylaP S, Ajmal KhanS (2013). The distribution and diversity of culturable aerobic heterotrophic benthic bacteria in the continental slope of the Bay of Bengal: Linked abiotic factors, including a tsunami. Russ J Mar Biol, 39(3): 169–181

13 DawsonA G (1994). Geomorphological effects of tsunami run-up and backwash.Geomorphology, 10(1–4): 83–94

14 DechoA W, VisscherP T, ReidR P (2005). Production and cycling of natural microbial exopolymers (EPS) within a marine stromatolite. Palaeogeogr Palaeoclimatol Palaeoecol, 219(1–2): 71–86

15 DragovićS, MihailovićN, GajićB (2008). Heavy metals in soils: distribution, relationship with soil characteristics and radionuclides and multivariate assessment of contamination sources. Chemosphere, 72(3): 491–495

PMID

16 DucklowH W, HillS M (1985). Tritiated thymidine incorporation and the growth of heterotrophic bacteria in warm core rings’. Limnol Oceanogr, 30(2): 260–272

17 GerbaC P, SchaibergerG E (1975). Effect of particulates on virus survival in seawater. J Water Pollut Control Fed, 47(1): 93–103

PMID

18 GrimesD J (1975). Release of sediment-bound fecal coliforms by dredging. Appl Microbiol, 29(1): 109–111

PMID

19 HollibaughJ T, CarruthersA B, FuhrmanJ A, AzamF (1980). Cycling of organic nitrogen inmarine plankton communities studied in enclosed water columns. Mar Biol, 59(1): 15–21

20 JolliffeI T (1986). Principal Component Analysis, Springer, New York.

21 KonnoE (1961). Geological observations of the Sanriku coastal region damaged by the tsunami due to the Chile earthquake in 1960. Contributions to the Institute of Geology and Paleontology. Tohoku University, 52: 1–40

22 LevintonJ S (2001). Marine Biology Function, Biodiversity and Ecology, 2nd ed. New York: Oxford University Press,PP. 515

23 LiY, GouX, WangG, ZhangQ, SuQ, XiaoG (2008). Heavy metal contamination and source in arid agricultural soil in central Gansu Province, China. J Environ Sci (China), 20(5): 607–612

PMID

24 LindowS E, BrandlM T (2003). Microbiology of the phyllosphere. Appl Environ Microbiol, 69(4): 1875–1883

PMID

25 MahalakshmiM, SrinivasanM, MuruganM, balakrishnanS, DevanathanK (2011). Isolation and identification of total Heterotrophic Bacteria and human pathogens in water and sediment from cuddalore fishing harbour after the tsunami. Asian J Biol Sci, 4: 148–156

26 MinouraK, NakayaS (1991). Traces of tsunami preserved in intertidal lacustrine and marsh deposits: some examples from northeast Japan. J Geol, 99(2): 265–287

27 MohanachandranG, SubramanianV (1990). Texture, mineralogy and elemental composition of sediments along the southeast coast of India. Indian J Mar Sci, 19: 128–132

28 NagendraR, KamalakannanB V, SajithC, SenG, ReddyA N, SrinivasaluS (2005). A record of foraminiferal assemblage in tsunami sediments along Nagappattinam Coast, Tamil Nadu. Curr Sci, 89(11): 1947–1952

29 PaulE A, ClarkF E (1998). Soil microbiology and biochemistry. NewYork: Academic.press: 2nd Edition

30 RajendranK, RajendranC P, Anil Earnest (2005). The great Sumathra Andaman earthquake of 26 December 2004. Curr Sci, 88(1): 11–12

31 RameshS, JayaprakashvelM, MathivananN (2006). Microbial status in seawater and coastal sediments during pre- and post-tsunami periods in the Bay of Bengal, India. Mar Ecol (Berl), 27(3): 198–203

32 RubioB, NombelaM A, VilasF (2000). Geochemistry of major and trace elements in sediments of the Ria de Vigo (NW Spain): an assessment of metal pollution. Mar Pollut Bull, 11(11): 968–980

33 SarmaV V B, MurtyV S N, RaoD P (1990). Distribution of cyclone heat potential in the Bay of Bengal. Indian J Mar Sci, 19: 102–106

34 ScheffersA, KelletatD (2003). Sedimentologic and geomorphologic tsunami imprints worldwide—a review. Earth Sci Rev, 63(1–2): 83–92

35 SrinivasaluS, Rajeshwara-RaoN, ThangaduraiN, JonathanM P, RoyP D, Ram-MohanV, SaravananP (2009) Characteristics of 2004 tsunami deposits of northern Tamil Nadu coast, India. Boletındela Sociedad Geolo’gica Mexicana

36 SrinivasaluS, ThangaduraiN, JonathanM P, Armstrong-AltrinJ S, AyyamperumalT, Ram MohanV (2008). Evaluation of trace metal enrichments from the 26 December 2004 tsunami sediments along southeast coast of India. Env Geol, 53(8): 1711–1721

37 SrinivasaluS, ThangaduraiN, SwitzerA D, Ram MohanV, AyyamperumalT (2007). Erosion and sedimentation in Kalpakkam (N Tamil Nadu, India) from the 26th December 2004 M9 tsunami.Mar Geol, 240(1–4): 65–75

38 Stephen-PichaimaniV, JonathanM P, SrinivasaluS, Rajeshwara-RaoN R, MohanS P (2008). Enrichment of trace metals in surface sediments from northern part of Point Calimere, SE coast of India. Env Geol, 55(8): 1811–1819

39 SubramaniR, ManiJ, NarayanasamyM (2006). Microbial status in sea water and coastal sediments during pre and post-tsunami periods in the Bay of Bengal, India. Marine Ecology, 27(3): 198–203

40 Surjit DasP S, Lyla, Ajmal KhanS (2005). Variation in microbial diversity in a Mangrove Ecosystem in Parangipettai coast (Southeast coast of India): Effect of Tsunami? Res. J. Chem Environ, 9: 46–49

41 ThistleD, WeatherlyG L, ErtmanS C (1995). Shelf harpacticoid copepods do not escape into the seabed during winter storms. J Mar Res, 53(5): 847–863

42 ThompsonF L, IidaT, SwingsJ (2004). Biodiversity of vibrios. Microbiol Mol Biol Rev, 68(3): 403–431

PMID

43 UrakawaH, YoshidaT, NishimuraM, OhwadaK (2000). Characterization of depth-related population variation in microbial communities of a coastal marine sediment using 16S rDNA-based approaches and quinone profiling. Environ Microbiol, 2(5): 542–554

PMID

44 Van BlaricomG R (1982). Experimental analysis of structural regulation in a marine sand community exposed to oceanic swell. Ecol Monogr, 52(3): 283–305

45 VasudevanV, SeetaramaswamyA (1983). Distribution of clay minerals in modern sediments of Palk Bay. Indian J Mar Sci, 12: 218–219

46 VieiraR H S F, RodriguesD P, MenezesE A, EvangelistaN S S, RiesE M F R, BarretoL M (2001). Microbial contamination of sand from major beaches in Fortaleza, Ceará state, Brazil. Braz J Microbiol, 32(2): 77–80

47 YamazakiT, YamaokaM, ShikiT (1989). Miocene offshore tractive current-worked conglomerates- Tsubutegaura, Chiba Peninsula, central Japan. Sediment Geol, 135: 231–239