Interneuron Dysfunction in Psychiatric Disorders

Overview

Journal Nat Rev Neurosci

Specialty Neurology

Date 2012 Jan 19

PMID 22251963

Citations 622

Authors

Oscar Marin

Affiliations

Soon will be listed here.

Abstract

Schizophrenia, autism and intellectual disabilities are best understood as spectrums of diseases that have broad sets of causes. However, it is becoming evident that these conditions also have overlapping phenotypes and genetics, which is suggestive of common deficits. In this context, the idea that the disruption of inhibitory circuits might be responsible for some of the clinical features of these disorders is gaining support. Recent studies in animal models demonstrate that the molecular basis of such disruption is linked to specific defects in the development and function of interneurons - the cells that are responsible for establishing inhibitory circuits in the brain. These insights are leading to a better understanding of the causes of schizophrenia, autism and intellectual disabilities, and may contribute to the development of more-effective therapeutic interventions.

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References

Mei L, Xiong W . Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci. 2008; 9(6):437-52. PMC: 2682371. DOI: 10.1038/nrn2392. View

Adachi M, Autry A, Covington 3rd H, Monteggia L . MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome. J Neurosci. 2009; 29(13):4218-27. PMC: 3005250. DOI: 10.1523/JNEUROSCI.4225-08.2009. View

Butt S, Sousa V, Fuccillo M, Hjerling-Leffler J, Miyoshi G, Kimura S . The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron. 2008; 59(5):722-32. PMC: 2562525. DOI: 10.1016/j.neuron.2008.07.031. View

Reeves R, Irving N, Moran T, WOHN A, Kitt C, Sisodia S . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995; 11(2):177-84. DOI: 10.1038/ng1095-177. View

Bakkaloglu B, ORoak B, Louvi A, Gupta A, Abelson J, Morgan T . Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet. 2008; 82(1):165-73. PMC: 2253974. DOI: 10.1016/j.ajhg.2007.09.017. View

Harrison P, Law A . Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry. 2006; 60(2):132-40. DOI: 10.1016/j.biopsych.2005.11.002. View

Poliak S, Peles E . The local differentiation of myelinated axons at nodes of Ranvier. Nat Rev Neurosci. 2003; 4(12):968-80. DOI: 10.1038/nrn1253. View

Fazzari P, Paternain A, Valiente M, Pla R, Lujan R, Lloyd K . Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature. 2010; 464(7293):1376-80. DOI: 10.1038/nature08928. View

Daviss S, Lewis D . Local circuit neurons of the prefrontal cortex in schizophrenia: selective increase in the density of calbindin-immunoreactive neurons. Psychiatry Res. 1995; 59(1-2):81-96. DOI: 10.1016/0165-1781(95)02720-3. View

10.

Semple D, McIntosh A, Lawrie S . Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol. 2005; 19(2):187-94. DOI: 10.1177/0269881105049040. View

11.

Shadlen M, Newsome W . Noise, neural codes and cortical organization. Curr Opin Neurobiol. 1994; 4(4):569-79. DOI: 10.1016/0959-4388(94)90059-0. View

12.

Vernes S, Newbury D, Abrahams B, Winchester L, Nicod J, Groszer M . A functional genetic link between distinct developmental language disorders. N Engl J Med. 2008; 359(22):2337-45. PMC: 2756409. DOI: 10.1056/NEJMoa0802828. View

13.

Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard M . X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet. 2004; 74(3):552-7. PMC: 1182268. DOI: 10.1086/382137. View

14.

Egawa K, Asahina N, Shiraishi H, Kamada K, Takeuchi F, Nakane S . Aberrant somatosensory-evoked responses imply GABAergic dysfunction in Angelman syndrome. Neuroimage. 2007; 39(2):593-9. DOI: 10.1016/j.neuroimage.2007.09.006. View

15.

Katona I, Freund T . Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med. 2008; 14(9):923-30. DOI: 10.1038/nm.f.1869. View

16.

Wen L, Lu Y, Zhu X, Li X, Woo R, Chen Y . Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons. Proc Natl Acad Sci U S A. 2010; 107(3):1211-6. PMC: 2824309. DOI: 10.1073/pnas.0910302107. View

17.

Shilyansky C, Lee Y, Silva A . Molecular and cellular mechanisms of learning disabilities: a focus on NF1. Annu Rev Neurosci. 2010; 33:221-43. PMC: 3063104. DOI: 10.1146/annurev-neuro-060909-153215. View

18.

Hashimoto T, Volk D, Eggan S, Mirnics K, Pierri J, Sun Z . Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci. 2003; 23(15):6315-26. PMC: 6740534. View

19.

Moessner R, Marshall C, Sutcliffe J, Skaug J, Pinto D, Vincent J . Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007; 81(6):1289-97. PMC: 2276348. DOI: 10.1086/522590. View

20.

Woo T, WHITEHEAD R, Melchitzky D, Lewis D . A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci U S A. 1998; 95(9):5341-6. PMC: 20262. DOI: 10.1073/pnas.95.9.5341. View