Assessment of Murine Startle Reactivity, Prepulse Inhibition, and Habituation

Mark A. Geyer1, Stephanie C. Dulawa2

1 University of California at San Diego, La Jolla, California, 2 Columbia University, New York, New York
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 8.17
DOI:  10.1002/0471142301.ns0817s24
Online Posting Date:  November, 2003
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Abstract

The study of the startle response and its plasticity provides a powerful research paradigm for examining the neural control of behavior. The neural substrates underlying phenomena such as informationā€processing functions, including sensorimotor gating, affective modulation, and habituation, can be studied using startle plasticity as an operational measure. The mouse is rapidly becoming the most powerful model system for the study of human CNS function and is highly amenable to both genetic and pharmacological study. This unit describes procedures for the assessment of the startle response to acoustic stimuli in mice; methods for assessing prepulse inhibition (PPI) of startle, with treatments including drug administration and genetic manipulation; and methods for testing habituation.

     
 
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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Acoustic Startle Reactivity in Mice
  • Basic Protocol 2: Prepulse Inhibition of the Startle Response
  • Alternate Protocol 1: Basic Test of Drug Effects on Prepulse Inhibition in Mice
  • Alternate Protocol 2: Habituation of the Startle Response in Mice
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Acoustic Startle Reactivity in Mice

  Materials
  • 25‐ to 30‐g naive wild‐type 129Sv mice
  • SR‐LAB startle apparatus with digitized electronic output (e.g., San Diego Instruments)
  • Calibrated sound level meter (e.g., Quest)

Basic Protocol 2: Prepulse Inhibition of the Startle Response

  Materials
  • 25‐ to 30‐g naive wild‐type and genetically altered 129Sv mice
  • SR‐LAB startle apparatus with digitized electronic output (e.g., San Diego Instruments)
  • Calibrated sound level meter (e.g., Quest)
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Figures

Videos

Literature Cited

Literature Cited
   Arieti, S. 1955. Interpretation of Schizophrenia. Brunner, New York.
   Bolino, F., Manna, V., Di Cicco, L., Di Michele, V., Daneluzzo, E., Rossi, A., and Casacchia, M. 1992. Startle reflex habituation in functional psychosis: A controlled study. Neurosci. Lett. 145:126‐128.
   Braff, D.L. and Geyer, M.A. 1990. Sensorimotor gating and schizophrenia: Human and animal model studies. Arch. Gen. Psychiatry 47:181‐188.
   Braff, D.L., Grillon, C., and Geyer, M.A. 1992. Gating and habituation of the startle reflex in schizophrenic patients. Arch. Gen. Psychiatry 49:206‐215.
   Braff, D.L., Geyer, M.A., and Swerdlow, N.R. 2001. Human studies of prepulse inhibition startle: Normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156:234‐258.
   Braff, D.L., Geyer, M.A., and Swerdlow, N.R. 2003. Human studies of prepulse inhibition of startle: Normal subjects, patient groups, and pharmacological studies. Psychopharmacology In press.
   Cadenhead, K.S., Geyer, M.A., and Braff, D.L. 1993. Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. Am. J. Psychiatry 180:1862‐1870.
   Davis, M. and Sollberger, A. 1971. Twenty‐four hour periodicity of the startle response in rats. Psychon. Sci. 25:1.
   Davis, M., Gendelman, D., Tischler, M., and Gendelman, P.A. 1982. Primary acoustic startle circuit: Lesion and stimulation studies. J. Neurosci. 2:791‐805.
   Davis, M., Walker, D.L., and Lee, Y. 1999. Neurophysiology and neuropharmacology of startle and its affective modulation. In Startle Modification: Implications for Neuroscience, Cognitive Science, and Clinical Science (M.E. Dawson, A.M. Schell, A.H. Bohmelt, eds.) Cambridge University Press, New York.
   Doetschman, T.C., Gregg, R.G., Maeda, N., Hooper, M.L., Melton, D., Thompson, S., and Smithies, O. 1987. Targeted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330:576‐578.
   Donavan, J. and Brown, P. 1995. Handling and restraint. In Current Protocols in Immunology (J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, and, W. Strober, eds.) pp. 1.3.1‐1.3.5. John Wiley & Sons, Hoboken, N.J.
   Duerr, J.S. and Quinn, W.G. 1982. Three Drosophila mutations that block associative learning also affect habituation and sensitization. Proc. Nat. Acad. Sci. U.S.A. 79:3646‐3650.
   Dulawa, S.C. and Geyer, M.A. 1996. Psychopharmacology of prepulse inhibition in mice. Chin. J. Physiol. 39:1‐8.
   Dulawa, S.C. and Geyer, M.A. 2000. Effects of strain and serotonergic agents on prepulse inhibition and habituation in mice. Neuropharmacology 39:2170‐2179.
   Dulawa, S.C., Hen, R., Scearce‐Levie, K., and Geyer, M.A. 1997. Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse inhibition in wild type and serotonin1B knockout mice. Psychopharmacology 132:125‐134.
   Dulawa, S.C., Hen, R., Scearce‐Levie, K., and Geyer, M.A. 1998. Serotonin1B receptor modulation of prepulse inhibition: Recent findings in wild type and 5‐HT1B knockout mice. Ann. N.Y. Acad. Sci. 861:79‐84.
   Dulawa, S.C., Gross, C., Stark, K., Hen, R., and Geyer, M.A. 2000a. Knockout mice reveal opposite roles for 5‐HT1A and 1B receptors in prepulse inhibition. Neuropsychopharmacology 22:650‐659.
   Dulawa, S.C., Scearce‐Levie, K., Hen, R., and Geyer, M.A. 2000b. Serotonin releasers increase prepulse inhibition in serotonin 1B knockout mice. Psychopharmacology 149:306‐312.
   Evans, M.J. and Kaufman, M.H. 1981. Establishment or culture of pluripotent cells from mouse embryos. Nature 292:154‐156.
   Falls, W.A., Carlson, S., Turner, J.G., and Willott, J.F. 1997. Fear‐potentiated startle in two strains of inbred mice. Behav. Neurosci. 111:855‐61.
   Geyer, M.A. and Braff, D.L. 1982. Habituation of the blink reflex in normals and schizophrenic patients. Psychophysiology 19:1‐6.
   Geyer, M.A., Krebs‐Thomson, K., Braff, D.L., and Swerdlow, N.R. 2001. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: A decade in review. Psychopharmacology 156:117‐154.
   Geyer, M.A., McIlwain, K.L., and Paylor, R. 2002. Mouse genetic models for prepulse inhibition: An early review. Molec. Psych. 7:1039‐1053.
   Graham, F.K. 1975. The more or less startling effects of weak prestimuli. Psychophysiology 12:238‐248.
   Hawkins, R.D., Cohen, T.E., Greene, W., and Kandel, E.R. 1998. Relationships between dishabituation, sensitization, and inhibition of the gill‐ and siphon‐withdrawal reflex in Aplysia californica: Effects of response measure, test time, and training stimulus. Behav. Neurosci. 112:24‐38.
   Hoffman, H.S. and Ison, J.R. 1980. Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input. Psychol. Rev. 87:175‐189.
   Ison, J.R. and Hoffman, H.S. 1983. Reflex modification in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon. Psychol. Bull. 94:3‐17.
   Ison, J.R., McAdam, D.W., and Hammond, G.R. 1973. Latency and amplitude changes in the acoustic startle reflex of the rat produced by variation in auditory prestimulation. Physiol. Behav. 10:1035‐1039.
   Kehne, J.H., Padich, R.A., McCloskey, T.C., Taylor, V.L., and Schmidt, C.J. 1996. 5‐HT modulation of auditory and visual sensorimotor gating. 1. Effects of 5‐HT releasers on sound and light prepulse inhibition in Wistar rats. Psychopharmacology 124:95‐106.
   Martin, G.R. 1981. Isolation of a pluripotent cell line from early embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. U.S.A. 78:7634‐7638.
   McCaughran, J., Bell, J., and Hitzemann, R. 1999. On the relationships of high‐frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series. Behav. Genet. 29:21‐30.
   McGhie, A. and Chapman, J. 1961. Disorders of attention and perception in early schizophrenia. Br. J. Med. Psychol. 34:103‐116.
   McKellar, P. 1957. Imagination and thinking. Cohen and West, London.
   Paylor, R. and Crawley, J.N. 1997. Inbred strain differences in prepulse inhibition of the mouse startle response. Psychopharmacology 132:169‐180.
   Payne, R.W., Mattussek, P., and George, E.I. 1959. An experimental study of schizophrenic thought disorder. J. Mental Sci. 105:440.
   Perry, W., Geyer, M.A., and Braff, D.L. 1999. Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients. Arch. Gen. Psychiatry 56:277‐281.
   Ralph, R.J., Paulus, M.P., and Geyer, M.A. 2001. Strain‐specific effects of amphetamine on prepulse inhibition and patterns of locomotor behavior in mice. J. Pharm. Exp. Ther. 298:148‐155.
   Ralph‐Williams, R.J., Lehmann‐Masten, V., Otero‐Corchon, V., Low, M.J., and Geyer, M.A 2002. Differential effects of direct and indirect dopamine agonists on prepulse inhibition: A study in D1 and D2 receptor knockout mice. J. Neurosci. 22:9604‐9611.
   Ralph‐Williams, R.J., Lehmann‐Masten, V., and Geyer, M.A. 2003. Dopamine D1 rather than D2 receptor agonists disrupt prepulse inhibition of startle in mice. Neuropsychopharmacology 28:108‐118.
   Rigdon, G.C. and Weatherspoon, J. 1992. 5‐HT1A receptor agonists block prepulse inhibition of the acoustic startle reflex. J. Pharm. Exp. Ther. 263:486‐493.
   Risbrough, V.B., Brodkin, J.D., and Geyer, M.A. 2003a. GABA‐A and 5‐HT1 A receptor agonists block expression of fear‐potentiated startle in mice. Neuropsychopharmacology 28:654‐663.
   Risbrough, V.B., Hauger, R.L., Pellymounter, M.A., and Geyer, M.A. 2003b. Dopamine D1 rather than D2 receptor agonists disrupt prepulse inhibition of startle in mice. Neuropsychopharmacology 28:654‐663.
   Sipes, T.A. and Geyer, M.A. 1995. 8‐OH‐DPAT disruption of prepulse inhibition in rats: reversal with (+)WAY 100,135 and localization of site of action. Psychopharmacology 117:41‐48.
   Swerdlow, N.R. and Geyer, M.A. 1999. Neurophysiology and neuropharmacology of short lead interval startle modification. In Startle Modification: Implications for Neuroscience, Cognitive Science, and Clinical Science. (M.E. Dawson, A.M. Schell, and, A.H. Bohmelt, eds.) pp. 114‐133. Cambridge University Press, Cambridge, New York.
   Swerdlow, N.R., Geyer, M.A., and Braff, D.L. 2001. Neural circuitry of prepulse inhibition of startle in the rat: Current knowledge and future challenges. Psychopharmacology 156:194‐215.
   Thomas, K.R. and Capecchi, M.R. 1987. Site‐directed mutagenesis by gene targeting in mouse embryo‐derived stem cells. Cell 51:503‐512.
   Thorpe, W.H. 1956. Learning and instinct in animals. Harvard University Press, Cambridge, Mass.
   Varty, G.B., Walters, N., Cohen‐Williams, M., and Carey, G.J. 2001. Comparison of apomorphine, amphetamine and dizocilpine disruptions of prepulse inhibition in inbred and outbred mice strains. Eur. J. Pharmacol. 424:27‐36.
   Waterson, R.H., et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature. 420:520‐562.
   Willott, J.F., Carlson, S., and Chen, H. 1994. Prepulse inhibition of the startle response in mice: Relationship to hearing loss and auditory system plasticity. Behav. Neurosci. 108:703‐713.
   Willott, J.F.; Erway, L.C.; Archer, J.R., and Harrison, D.E. 1995. Genetics of age‐related hearing loss in mice. II. Strain differences and effects of caloric restriction on cochlear pathology and evoked response thresholds. Hear. Res. 88:143‐155.
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