Intense sound-induced plasticity in the dorsal cochlear nucleus of rats: evidence for cholinergic receptor upregulation

Hear Res. 2007 Apr;226(1-2):232-43. doi: 10.1016/j.heares.2006.07.001. Epub 2006 Aug 17.

Abstract

Previous studies in a number of species have demonstrated that spontaneous activity in the dorsal cochlear nucleus (DCN) becomes elevated following exposure to intense sound. This condition of hyperactivity has aroused considerable interest because it may represent an important neural correlate of tinnitus. There is some evidence that neurons in the superficial DCN, such as cartwheel, stellate and fusiform cells, may contribute to the level of hyperactivity induced by intense sound, although the relative importance of these different cell types is unknown. In the present study, we sought to determine the effect of intense sound exposure on multiunit spontaneous activity both at the DCN surface and in the fusiform cell layer and to examine the influence of cholinergic input to DCN circuits on the level of activity in the fusiform cell layer. Rats were studied in two groups, one of which had been exposed to a continuous intense sound (10 kHz 127 dB SPL) for 4h while the other group served as unexposed controls. Between 30 and 52 days post-exposure, recordings of multiunit activity were performed at the DCN surface as well as in the middle of the fusiform cell layer. Changes in fusiform cell layer activity were also studied in response to superficial applications of the cholinergic agonist, carbachol, either alone or following pre-application of the cholinergic antagonist, atropine. The results demonstrated that multiunit spontaneous activity in the rat DCN was generally much higher in both control and exposed animals relative to that which has been observed in other species. This activity was significantly higher at the DCN surface of sound-exposed animals than that of controls. In contrast, hyperactivity could not be demonstrated in the fusiform cell layer of sound-exposed animals. Carbachol administration most commonly caused suppression of fusiform cell layer activity. However, this suppression was considerably stronger in the DCN of sound-exposed animals than in controls. These findings suggest that, hyperactivity at the DCN surface of exposed rats may arise as a consequence of more highly activated neurons in the molecular layer, such as cartwheel and/or stellate cells, and that the lack of hyperactivity in the fusiform cell layer may be the result of inhibition of fusiform cells by these inhibitory interneurons. Although this finding does not rule out fusiform cells as possible sources of hyperactivity in other species, or even in the rat after short post-exposure recovery periods, the enhanced sensitivity of the fusiform cell layer to cholinergic stimulation suggests that in the rat, at least after prolonged post-exposure recovery periods, increased inhibition of activity in this layer by more superficially located neurons may result from an upregulation of receptors for cholinergic input. This upregulation may be greater in rats than in other species due to the relatively heavy cholinergic input that exists in the cochlear nucleus of this species.

Publication types

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

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Atropine / pharmacology
  • Carbachol / pharmacology
  • Cochlear Nucleus / drug effects
  • Cochlear Nucleus / physiopathology*
  • Disease Models, Animal
  • Electrophysiology
  • Neuronal Plasticity
  • Noise / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cholinergic / physiology*
  • Tinnitus / etiology*
  • Tinnitus / physiopathology*
  • Up-Regulation

Substances

  • Receptors, Cholinergic
  • Atropine
  • Carbachol