Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the mediation of prepulse inhibition of the acoustic startle response in the rat

Exp Brain Res. 1993;97(1):71-82. doi: 10.1007/BF00228818.


The amplitude of the acoustic startle response (ASR) is markedly reduced when the startle eliciting pulse is preceded by a weak, non-startling stimulus at an appropriate lead time, usually about 100 ms. This phenomenon is termed prepulse inhibition (PPI) and has received considerable attention in recent years as a model of sensorimotor gating. We report here on experiments which were undertaken in order to investigate some of the neural mechanisms of PPI. We focused on the characterization of the cholinergic innervation of the pontine reticular nucleus, caudal part (PnC), an obligatory relay station in the primary startle pathway. The combination of retrograde tracing with choline acetyltransferase-immunocytochemistry revealed a cholinergic projection from the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) to the PnC. Extracellular recording from single PnC units, combined with microiontophoretic application of the acetylcholine (ACh) agonists acetyl-beta-methylcholine (AMCH) and carbachol revealed that ACh inhibits the majority of acoustically responsive PnC neurons. Neurotoxic lesions of the cholinergic neurons of the PPTg significantly reduced PPI without affecting the ASR amplitude in the absence of prepulses. No effect on long-term habituation of the ASR was observed. The present data indicate that the pathway mediating PPI impinges upon the primary acoustic startle circuit through an inhibitory cholinergic projection from the PPTg to the PnC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Choline O-Acetyltransferase / immunology
  • Choline O-Acetyltransferase / metabolism
  • Electrophysiology
  • Immunohistochemistry
  • Iontophoresis
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Parasympathetic Nervous System / cytology
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / physiology*
  • Parasympathomimetics / pharmacology
  • Pons / cytology
  • Pons / drug effects
  • Pons / physiology*
  • Quinolinic Acid / toxicity
  • Rats
  • Rats, Wistar
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology*
  • Tegmentum Mesencephali / cytology
  • Tegmentum Mesencephali / drug effects
  • Tegmentum Mesencephali / physiology*


  • Parasympathomimetics
  • Choline O-Acetyltransferase
  • Quinolinic Acid