Pre-Pulse Inhibition

LSID: http://syli.cz/urn:lsid:public.sylics.com:conventionaltest:E3D8-7G43-B254

Materials and Methods
Mice were singly housed on sawdust in standard Makrolon type II cages enriched with cardboard nesting material for at least one week prior to experiments, with water and food ad libitum (7:00/19:00 lights on/off; providing an abrupt phase transition).

Associated Mammalian Phenotype Ontologies (MGI)
- MP:0003088 abnormal prepulse inhibition
- MP:0001486 abnormal startle reflex

Acoustic startle and prepulse inhibition
Acoustic startle and PPI [1] were measured during one 45 min session in four Plexiglas cylinders in ventilated sound-attenuating chambers (Med Associates, St. Albans, VT), placed on separate passive heavy vibration-free tables (Newport Corporation, Irvine, CA). During testing, a separate speaker provided white noise background of 65 dB. The intensity of the startle stimuli was calibrated with a microphone placed inside the Plexiglas cylinders in a closed chamber, while white background noise was switched off. Hence, the reported prepulse and pulse intensities are lower than the actual cumulative sound pressure level during testing (e.g., a 65 dB pulse in addition to a 65 dB background noise add up to 68.01 dB). The session started with a habituation period of 5 min, followed by a total of 260 trials with pseudo randomized interval periods (5 - 15 s) consisting of acoustic startle trials with white noise bursts at various intensities (65, 70, 75, 80, 85, 90, 95, 100, 105, 110, and 115 dB; 10 trials per intensity) and prepulse inhibition trials with white noise bursts at various prepulse intensities (0, 65, 67, 71 and 79 dB; 30 trials per prepulse intensity; startle intensity always 120 dB) in pseudo randomized order such that all 4 boxes produced startle stimuli at exactly the same time. In half of the prepulse trials, onset of white noise prepulse stimuli (20 ms; 1 ms programmed rise/fall time) and startle stimuli (40 ms; no programmed rise/fall time) was separated by a 30 ms, in the other half by 100 ms interval. In each trial, the highest startle intensity peak (in relative machine units) was collected during the 100 ms interval after the startle stimulus, from which the individual mean highest startle intensity peak during the 100 ms null-period prior to prepulse stimuli was subtracted. The inter-stimulus interval (ISI) of 30ms was used as the PPI in mice is at its maximum around 30ms ISI [2], whereas for humans the maximum PPI is found at 100ms [3]. The startle sensitivity was determined for each mouse by determining the startle threshold at which a statistically significant startle response was measured (one-sample t-test, with average null-period as reference value). The equipment was calibrated to allow for a wide range of startle intensities, however, the force generated by some mice at the highest pulse intensities could exceed the dynamic range of the equipment (maximum of 2047 units) artificially reducing the percentage of PPI in subsequent analyses. Therefore, when the number of such censored 120 dB pulse trials was more than 33% (e.g., more than 5 out of 15) no PPI was calculated. The percentage of PPI was calculated as follows: PPI = 100 * [(mean startle intensity pulse) - (mean startle intensity pulse with prepulse) / (mean startle intensity pulse)].

1. Swerdlow, N. R., Braff, D. L. & Geyer, M. a. Animal models of deficient sensorimotor gating: what we know, what we think we know, and what we hope to know soon. Behav. Pharmacol. 11, 185-204 (2000).
2. Yeomans, J. S. et al. GABA receptors and prepulse inhibition of acoustic startle in mice and rats. Eur. J. Neurosci. 31, 2053-61 (2010).
3. Braff, D., Grillon, C. & Geyer, M. Gating and habituation of the startle reflex in schizophrenic patients. Arch. Gen. Psychiatry 0804, (1992).

Parameter information
Parameter nameUnits
Average startle response per block at 120dBNA
*Average startle response 65-120dBNA
PPI at 30ms ISI%PPI
PPI at 100ms ISI%PPI
*Startle ThresholddB
Average PPI at 30ms ISI%PPI
Average PPI at 100ms ISI%PPI
*PPI at 65 dB - 100ms ISI%PPI
*PPI at 65 dB - 30ms ISI%PPI
Average startle response 65-85dBNA