Genetic Models of Sensorimotor Gating: Relevance to Neuropsychiatric Disorders

Overview

Journal Curr Top Behav Neurosci

Publisher Springer

Specialty Psychology

Date 2012 Feb 28

PMID 22367921

Citations 54

Authors

Susan B Powell

Martin Weber

Mark A Geyer

Affiliations

Soon will be listed here.

Abstract

Sensorimotor gating, or the ability of a sensory event to suppress a motor response, can be measured operationally via prepulse inhibition (PPI) of the startle response. PPI is deficient in schizophrenia patients as well as other neuropsychiatric disorders, can be measured across species, and has been used widely as a translational tool in preclinical neuropharmacological and genetic research. First developed to assess drug effects in pharmacological and developmental models, PPI has become one of the standard behavioral measures in genetic models of schizophrenia and other neuropsychiatric disorders that exhibit PPI deficits. In this chapter we review the literature on genetic models of sensorimotor gating and discuss the utility of PPI as a tool in phenotyping mutant mouse models. We highlight the approaches to genetic mouse models of neuropsychiatric disease, discuss some of the important caveats to these approaches, and provide a comprehensive table covering the more recent genetic models that have evaluated PPI.

Citing Articles

Neuronal subset-specific -deficient mice do not exhibit deficits in sensorimotor gating processes.

Binder M, Nolan S, Lugo J F1000Res. 2025; 8:1727.

PMID: 39822947 PMC: 11736557. DOI: 10.12688/f1000research.20604.3.

The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.

Lipari N, Galfano A, Venkatesh S, Grezenko H, Sandoval I, Manfredsson F Front Neural Circuits. 2024; 18:1463941.

PMID: 39634948 PMC: 11615880. DOI: 10.3389/fncir.2024.1463941.

Psychedelics action and schizophrenia.

Mackowiak M Pharmacol Rep. 2023; 75(6):1350-1361.

PMID: 37899392 PMC: 10661800. DOI: 10.1007/s43440-023-00546-5.

Prepulse inhibition deficit as a transdiagnostic process in neuropsychiatric disorders: a systematic review.

Santos-Carrasco D, De La Casa L BMC Psychol. 2023; 11(1):226.

PMID: 37550772 PMC: 10408198. DOI: 10.1186/s40359-023-01253-9.

Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating.

Ho E, Welch A, Thompson S, Knowles J, Dulawa S PLoS One. 2023; 18(5):e0277446.

PMID: 37205689 PMC: 10198499. DOI: 10.1371/journal.pone.0277446.

References

Porteous D, Thomson P, Brandon N, Kirsty Millar J . The genetics and biology of DISC1--an emerging role in psychosis and cognition. Biol Psychiatry. 2006; 60(2):123-31. DOI: 10.1016/j.biopsych.2006.04.008. 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

Chen H, Stoker A, Markou A . The glutamatergic compounds sarcosine and N-acetylcysteine ameliorate prepulse inhibition deficits in metabotropic glutamate 5 receptor knockout mice. Psychopharmacology (Berl). 2010; 209(4):343-50. PMC: 2855017. DOI: 10.1007/s00213-010-1802-2. View

Feifel D, Pang Z, Shilling P, Melendez G, Schreiber R, Button D . Sensorimotor gating in neurotensin-1 receptor null mice. Neuropharmacology. 2009; 58(1):173-8. PMC: 2784210. DOI: 10.1016/j.neuropharm.2009.07.002. View

Zhu H, Mingler M, McBride M, Murphy A, Valenzuela D, Yancopoulos G . Abnormal response to stress and impaired NPS-induced hyperlocomotion, anxiolytic effect and corticosterone increase in mice lacking NPSR1. Psychoneuroendocrinology. 2010; 35(8):1119-32. PMC: 2888805. DOI: 10.1016/j.psyneuen.2010.01.012. View

Brzozka M, Radyushkin K, Wichert S, Ehrenreich H, Rossner M . Cognitive and sensorimotor gating impairments in transgenic mice overexpressing the schizophrenia susceptibility gene Tcf4 in the brain. Biol Psychiatry. 2010; 68(1):33-40. DOI: 10.1016/j.biopsych.2010.03.015. View

Braff D . Prepulse inhibition of the startle reflex: a window on the brain in schizophrenia. Curr Top Behav Neurosci. 2011; 4:349-71. DOI: 10.1007/7854_2010_61. View

Geyer M, Dulawa S . Assessment of murine startle reactivity, prepulse inhibition, and habituation. Curr Protoc Neurosci. 2008; Chapter 8:Unit 8.17. DOI: 10.1002/0471142301.ns0817s24. View

Smith C, Lawrence A, Sutton S, Gundlach A . Behavioral phenotyping of mixed background (129S5:B6) relaxin-3 knockout mice. Ann N Y Acad Sci. 2009; 1160:236-41. DOI: 10.1111/j.1749-6632.2009.03953.x. View

10.

Green M, Butler P, Chen Y, Geyer M, Silverstein S, Wynn J . Perception measurement in clinical trials of schizophrenia: promising paradigms from CNTRICS. Schizophr Bull. 2008; 35(1):163-81. PMC: 2635893. DOI: 10.1093/schbul/sbn156. View

11.

Lipina T, Kaidanovich-Beilin O, Patel S, Wang M, Clapcote S, Liu F . Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3. Synapse. 2010; 65(3):234-48. PMC: 4485461. DOI: 10.1002/syn.20839. View

12.

Weinberger D, Berman K, Suddath R, Torrey E . Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry. 1992; 149(7):890-7. DOI: 10.1176/ajp.149.7.890. View

13.

Karper L, Freeman G, Grillon C, Morgan 3rd C, Charney D, Krystal J . Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis. J Neuropsychiatry Clin Neurosci. 1996; 8(1):60-6. DOI: 10.1176/jnp.8.1.60. View

14.

Wang X . Cre transgenic mouse lines. Methods Mol Biol. 2009; 561:265-73. DOI: 10.1007/978-1-60327-019-9_17. View

15.

Tarantino L, Bucan M . Dissection of behavior and psychiatric disorders using the mouse as a model. Hum Mol Genet. 2000; 9(6):953-65. DOI: 10.1093/hmg/9.6.953. View

16.

Barros C, Calabrese B, Chamero P, Roberts A, Korzus E, Lloyd K . Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. Proc Natl Acad Sci U S A. 2009; 106(11):4507-12. PMC: 2657442. DOI: 10.1073/pnas.0900355106. View

17.

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

18.

Braff D, Grillon C, Geyer M . Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry. 1992; 49(3):206-15. DOI: 10.1001/archpsyc.1992.01820030038005. View

19.

McOmish C, Burrows E, Howard M, Scarr E, Kim D, Shin H . Phospholipase C-beta1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration. Mol Psychiatry. 2007; 13(7):661-72. DOI: 10.1038/sj.mp.4002046. View

20.

Duncan G, Moy S, Perez A, Eddy D, Zinzow W, Lieberman J . Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function. Behav Brain Res. 2004; 153(2):507-19. DOI: 10.1016/j.bbr.2004.01.008. View