RIM1alpha and Interacting Proteins Involved in Presynaptic Plasticity Mediate Prepulse Inhibition and Additional Behaviors Linked to Schizophrenia

Overview

Journal J Neurosci

Specialty Neurology

Date 2010 Apr 16

PMID 20392954

Citations 29

Authors

Jacqueline Blundell

Pascal S Kaeser

Thomas C Sudhof

Craig M Powell

Affiliations

Soon will be listed here.

Abstract

Several presynaptic proteins involved in neurotransmitter release in the CNS have been implicated in schizophrenia in human clinical genetic studies, in postmortem studies, and in studies of putative animal models of schizophrenia. The presynaptic protein RIM1alpha mediates presynaptic plasticity and cognitive function. We now demonstrate that mice deficient in RIM1alpha exhibit abnormalities in multiple schizophrenia-relevant behavioral tasks including prepulse inhibition, response to psychotomimetic drugs, and social interaction. These schizophrenia-relevant behavioral findings are relatively selective to RIM1alpha-deficient mice, as mice bearing mutations in the RIM1alpha binding partners Rab3A or synaptotagmin 1 only show decreased prepulse inhibition. In addition to RIM1alpha's involvement in multiple behavioral abnormalities, these data suggest that alterations in presynaptic forms of short-term plasticity are linked to alterations in prepulse inhibition, a measure of sensorimotor gating.

Citing Articles

Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes.

Laighneach A, Kelly J, Desbonnet L, Holleran L, Kerr D, McKernan D PLoS One. 2023; 18(12):e0295855.

PMID: 38127959 PMC: 10735045. DOI: 10.1371/journal.pone.0295855.

The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System.

Heitmann T, Barrow J Biomolecules. 2023; 13(9).

PMID: 37759717 PMC: 10526494. DOI: 10.3390/biom13091317.

A Critical Review of Zebrafish Neurological Disease Models-2. Application: Functional and Neuroanatomical Phenotyping Strategies and Chemical Screens.

Burton E, Burgess H Oxf Open Neurosci. 2023; 2.

PMID: 37637775 PMC: 10455049. DOI: 10.1093/oons/kvac019.

Effects of heterozygous deletion of autism-related gene Cullin-3 in mice.

Xia Q, Walker A, Song C, Wang J, Singh A, Mobley J PLoS One. 2023; 18(7):e0283299.

PMID: 37428799 PMC: 10332626. DOI: 10.1371/journal.pone.0283299.

Assessing olfactory, memory, social and circadian phenotypes associated with schizophrenia in a genetic model based on Rim.

Hidalgo S, Campusano J, Hodge J Transl Psychiatry. 2021; 11(1):292.

PMID: 34001859 PMC: 8128896. DOI: 10.1038/s41398-021-01418-3.

References

Ludewig K, Geyer M, Vollenweider F . Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Biol Psychiatry. 2003; 54(2):121-8. DOI: 10.1016/s0006-3223(02)01925-x. View

Stone J, Morrison P, Pilowsky L . Glutamate and dopamine dysregulation in schizophrenia--a synthesis and selective review. J Psychopharmacol. 2007; 21(4):440-52. DOI: 10.1177/0269881106073126. View

Glantz L, Lewis D . Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity. Arch Gen Psychiatry. 1997; 54(7):660-9. DOI: 10.1001/archpsyc.1997.01830190088009. View

Vawter M, Thatcher L, Usen N, Hyde T, Kleinman J, Freed W . Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia. Mol Psychiatry. 2002; 7(6):571-8. DOI: 10.1038/sj.mp.4001158. View

Braff D, Geyer M, Swerdlow N . Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl). 2001; 156(2-3):234-58. DOI: 10.1007/s002130100810. View

Lipska B, Weinberger D . To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology. 2000; 23(3):223-39. DOI: 10.1016/S0893-133X(00)00137-8. View

Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M . Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet. 2007; 17(3):458-65. DOI: 10.1093/hmg/ddm323. View

Mechri A, Saoud M, Khiari G, DAmato T, Dalery J, Gaha L . [Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine]. Encephale. 2001; 27(1):53-9. View

Geppert M, Goda Y, Stevens C, Sudhof T . The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature. 1997; 387(6635):810-4. DOI: 10.1038/42954. View

10.

Javitt D . Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol. 2007; 78:69-108. DOI: 10.1016/S0074-7742(06)78003-5. View

11.

Drew C, Kyd R, Morton A . Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal. Hum Mol Genet. 2007; 16(19):2288-305. DOI: 10.1093/hmg/ddm181. View

12.

Bucan M, Abrahams B, Wang K, Glessner J, Herman E, Sonnenblick L . Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet. 2009; 5(6):e1000536. PMC: 2695001. DOI: 10.1371/journal.pgen.1000536. View

13.

Coyle J . Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol. 2006; 26(4-6):365-84. PMC: 11881825. DOI: 10.1007/s10571-006-9062-8. View

14.

Glessner J, Wang K, Cai G, Korvatska O, Kim C, Wood S . Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009; 459(7246):569-73. PMC: 2925224. DOI: 10.1038/nature07953. View

15.

Gabriel S, Haroutunian V, Powchik P, Honer W, Davidson M, Davies P . Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia. Arch Gen Psychiatry. 1997; 54(6):559-66. DOI: 10.1001/archpsyc.1997.01830180077010. View

16.

Geppert M, Goda Y, Hammer R, Li C, Rosahl T, Stevens C . Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell. 1994; 79(4):717-27. DOI: 10.1016/0092-8674(94)90556-8. View

17.

Lee H, Song J, Kim J, Jin S, Hong M, Park J . Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia. Behav Brain Funct. 2005; 1:15. PMC: 1215472. DOI: 10.1186/1744-9081-1-15. View

18.

Bubenikova-Valesova V, Horacek J, Vrajova M, Hoschl C . Models of schizophrenia in humans and animals based on inhibition of NMDA receptors. Neurosci Biobehav Rev. 2008; 32(5):1014-23. DOI: 10.1016/j.neubiorev.2008.03.012. View

19.

Etherton M, Blaiss C, Powell C, Sudhof T . Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. Proc Natl Acad Sci U S A. 2009; 106(42):17998-8003. PMC: 2764944. DOI: 10.1073/pnas.0910297106. View

20.

Sodhi M, Wood K, Meador-Woodruff J . Role of glutamate in schizophrenia: integrating excitatory avenues of research. Expert Rev Neurother. 2008; 8(9):1389-406. DOI: 10.1586/14737175.8.9.1389. View