A fast cholinergic modulation of the primary acoustic startle circuit in rats

Brain Struct Funct. 2014 Sep;219(5):1555-73. doi: 10.1007/s00429-013-0585-8. Epub 2013 Jun 4.


Cochlear root neurons (CRNs) are the first brainstem neurons which initiate and participate in the full expression of the acoustic startle reflex. Although it has been suggested that a cholinergic pathway from the ventral nucleus of the trapezoid body (VNTB) conveys auditory prepulses to the CRNs, the neuronal origin of the VNTB-CRNs projection and the role it may play in the cochlear root nucleus remain uncertain. To determine the VNTB neuronal type which projects to CRNs, we performed tract-tracing experiments combined with mechanical lesions, and morphometric analyses. Our results indicate that a subpopulation of non-olivocochlear neurons projects directly and bilaterally to CRNs via the trapezoid body. We also performed a gene expression analysis of muscarinic and nicotinic receptors which indicates that CRNs contain a cholinergic receptor profile sufficient to mediate the modulation of CRN responses. Consequently, we investigated the effects of auditory prepulses on the neuronal activity of CRNs using extracellular recordings in vivo. Our results show that CRN responses are strongly inhibited by auditory prepulses. Unlike other neurons of the cochlear nucleus, the CRNs exhibited inhibition that depended on parameters of the auditory prepulse such as intensity and interstimulus interval, showing their strongest inhibition at short interstimulus intervals. In sum, our study supports the idea that CRNs are involved in the auditory prepulse inhibition of the acoustic startle reflex, and confirms the existence of multiple cholinergic pathways that modulate the primary acoustic startle circuit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Action Potentials / drug effects
  • Animals
  • Auditory Pathways / cytology
  • Auditory Pathways / physiology*
  • Biotin / analogs & derivatives
  • Biotin / metabolism
  • Calcium-Binding Proteins / metabolism
  • Cholinergic Agents / pharmacology*
  • Cholinergic Neurons / drug effects*
  • Cholinergic Neurons / physiology
  • Cochlear Nucleus / cytology*
  • Dextrans / metabolism
  • Female
  • Functional Laterality
  • Gene Expression / drug effects
  • Inferior Colliculi / physiology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / genetics
  • Receptors, Muscarinic / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism
  • Reflex, Startle / drug effects*
  • Reflex, Startle / physiology
  • Trapezoid Body / cytology*


  • Calcium-Binding Proteins
  • Cholinergic Agents
  • Dextrans
  • RNA, Messenger
  • Receptors, Muscarinic
  • Receptors, Nicotinic
  • biotinylated dextran amine
  • Biotin