PMID- 20497471 OWN - NLM STAT- MEDLINE DCOM- 20101025 LR - 20181201 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 31 IP - 11 DP - 2010 Jun TI - GABA receptors and prepulse inhibition of acoustic startle in mice and rats. PG - 2053-61 LID - 10.1111/j.1460-9568.2010.07236.x [doi] AB - The acoustic startle reflex is strongly inhibited by a moderate-intensity acoustic stimulus that precedes the startling stimulus by roughly 10-1000 ms (prepulse inhibition, PPI). At long interstimulus intervals (ISIs) of 100-1000 ms, PPI in rats is reduced by the muscarinic receptor antagonist scopolamine. Here, we studied the role of GABA receptors in PPI at full ISI ranges in both mice and rats. In B6 mice, PPI begins and ends at shorter ISIs (4 and 1000 ms, respectively) than in Wistar rats (8 and 5000 ms). The GABA(A) antagonist bicuculline (1 mg/kg i.p.) reduced PPI at ISIs near the peak of PPI in both rats and mice. The GABA(B) antagonist phaclofen (10 or 30 mg/kg i.p. in rats or mice, respectively) reduced PPI only at long ISIs, similar to the effects of the muscarinic antagonist scopolamine (1 mg/kg i.p.). The effects of phaclofen and scopolamine were additive in rats, suggesting independent effects of GABA(B) and muscarinic receptors. Patch-clamp recordings of startle-mediating PnC (nucleus reticularis pontis caudalis) giant neurons in rat slices show that EPSCs evoked by either trigeminal or auditory fiber stimulation were inhibited by the GABA(A/C) agonist muscimol or the GABA(B) agonist baclofen via postsynaptic mechanisms. Hyperpolarization of PnC neurons by muscimol was reversed with bicuculline, indicating that postsynaptic GABA(A) receptors strongly inhibit PnC giant neurons needed for startle. Therefore, GABA receptors on PnC giant neurons mediate a substantial part of PPI, with GABA(A) receptors contributing at the peak of PPI, and GABA(B) receptors adding to muscarinic effects on PPI at long ISIs. FAU - Yeomans, John S AU - Yeomans JS AD - Department of Psychology, Centre for Biological Timing and Cognition, University of Toronto, Toronto, Canada M5S 3G3. yeomans@psych.utoronto.ca FAU - Bosch, Daniel AU - Bosch D FAU - Alves, Nyresa AU - Alves N FAU - Daros, Alexander AU - Daros A FAU - Ure, Robert J AU - Ure RJ FAU - Schmid, Susanne AU - Schmid S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100524 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (GABA Agonists) RN - 0 (GABA Antagonists) RN - 0 (Muscarinic Antagonists) RN - 0 (Receptors, GABA) RN - 108351-35-5 (phaclofen) RN - 2763-96-4 (Muscimol) RN - DL48G20X8X (Scopolamine) RN - H789N3FKE8 (Baclofen) RN - Y37615DVKC (Bicuculline) SB - IM MH - *Acoustic Stimulation MH - Animals MH - Baclofen/analogs & derivatives/pharmacology MH - Bicuculline/pharmacology MH - GABA Agonists/pharmacology MH - GABA Antagonists/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Muscarinic Antagonists/pharmacology MH - Muscimol/pharmacology MH - Neural Inhibition/drug effects/*physiology MH - Neurons/drug effects/metabolism MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Rats, Wistar MH - Receptors, GABA/*metabolism MH - Reflex, Startle/drug effects/*physiology MH - Scopolamine/pharmacology MH - Time Factors EDAT- 2010/05/26 06:00 MHDA- 2010/10/26 06:00 CRDT- 2010/05/26 06:00 PHST- 2010/05/26 06:00 [entrez] PHST- 2010/05/26 06:00 [pubmed] PHST- 2010/10/26 06:00 [medline] AID - EJN7236 [pii] AID - 10.1111/j.1460-9568.2010.07236.x [doi] PST - ppublish SO - Eur J Neurosci. 2010 Jun;31(11):2053-61. doi: 10.1111/j.1460-9568.2010.07236.x. Epub 2010 May 24.