A.J.
MEDS5377
5/31/09
Paper 3
Inhibiting the Effects of Type II Neurons in the Commissural Connection between both Cochlear Nuclei
Introduction
In humans, the left and right cochlear nuclei (CN) are connected by a commissural pathway that may
relay diverse information contributing to binaural auditory signal processing. Previous studies have
shown that these commissural projections originate from multipolar cells throughout the ventral
cochlear nucleus (VCN) and evoke inhibitory IPSPs with more than a third of all major cell types of the
contralateral VCN, including at least some of those that project to the inferior colliculus[1]. These
neurons may be separated into their respective anatomical subtypes based on topographical
distributions in the VCN and the percent apposition (PA), which is the percentage of the soma apposed
by synaptic terminals [2]. The exact functions of these two neuron types are unknown: Current theories
indicate that Type I neurons may underlie slow regulatory influences that enhance binaural processing
or the recovery of function after injury. Most Type II neurons are found in the magnocellular core and
generate fast, monosynaptic inhibitory and glycinergic interactions. Still yet, the function of these Type II
neurons remains unclear. This study will focus on the function of the Type II commissural neurons with
respect to excessive sound stimulation.
Hypothesis
In the normal guinea pig, contralateral sound inhibits more than a third of the VCN neurons, but excites
less than 4% of these neurons. However, unilateral conductive hearing loss (CHL) and cochlear ablation
(CA) result in a major enhancement of contralateral excitation and a reduction of inhibition [3]. Since the
lack of sound input due to hearing loss or damage results in excess Type I neuron excitation and
decreased Type II neuron inhibition, I therefore hypothesize that the Type II commissural neurons relay
information about excess and arbitrary sound, such as background noise and echoes, to the
contralateral CN to inhibit their input to the auditory system at the level of the cochlea. When the Type
II commissural pathway is blocked, the rapid IPSPs normally generated in the contralateral CN will not
fire, and thus the response will not occur.
Method
In a healthy guinea pig I will first record the activity [what type of activity will you look at? Single
neurons, EEG, evoked potentials?] in the auditory cortex and also the area of the inferior colliculus that
the VCN sends projections when exposed to (a) high electrical stimulations of the cochlea and (b)
excessive sound stimuli. This will be the normal or standard model. Next I will treat the Type II
commissural neurons with the localized neurotoxin Genistein, a Glycine antagonist, in the magnocellular
core of the VCN on both sides of the head to inhibit the Glycine from the Type II commissural neurons
from synapsing. [This will block all glycine receptors in the area of the injection, not just the ones from
the type 2 commissural cells. This will reduce the specificity of the test. ] The rest of the cochlear nuclei
on both sides of the head will remain intact and function normally. Again, I will then stimulate (a)
electrically and then (b) with excessive sound, recording the activity in the auditory cortex and the
inferior colliculus. I will then compare the results with the normal, healthy guinea pig.
A.J.
MEDS5377
Expected Results/Discussion
If my hypothesis is correct I will see increased activity in both the auditory cortex and the inferior
colliculus when the Type II commissural neuron pathway in blocked compared to the standard, normal
guinea pig. This would indicate that excess sound such as echoes and background noise becomes
inhibited from further projecting to the auditory cortex at the level of the cochlea through the
commissural pathway. Thus Type II commissural neurons would help to refine the sound we perceive by
filtering out excess noise. My hypothesis will be rejected and the null hypothesis will be accepted if the
difference in the recordings is not statistically significant in the normal, healthy guinea pig compared to
when the commissural pathway was blocked with Genistein. This would indicate that the commissural
pathway plays little or no role in the refining of the sound we perceive. If the recordings are higher in
the auditory cortex but not the inferior colliculus when the VCN is treated with Genistein then my
hypothesis would also be rejected because this data would indicate that excess sound inhibition and
filtration occurs later in the auditory pathway, after the level of the inferior colliculus. Thus, further
studies would have to be carried out to determine the function of the Type II neurons of the
commissural connection.
Implications
A direct commissural connection formed between cochlear nuclei allows information from the
contralateral ear to rapidly influence the processing of the ascending auditory signal. If we better
understand the functions of these pathways and the sound we perceive we can learn how to solve
auditory problems associated with binaural hearing such as unilateral hearing loss (UHL) or single-sided
deafness (SSD).
[1]
Babalian, A. L., D. K. Ryugo, M. W. Vischer, and R. M. Rouiller. "Inhibitory synaptic interactions
between cochlear nuclei: evidence from an in vitro whole brain study." Neuroreport 10 (1999):
1913-917. Http://www.ncbi.nlm.nih.gov/pubmed/. 29 May 2009.
[2]
Doucet, J. R., N. M. Leniham, and B. J. May. "Commissural neurons in the rat ventral cochlear
nucleus." Http://www.ncbi.nlm.nih.gov.ezproxy.lib.uconn.edu/pubmed/ 10 (2009): 269-80.
PubMed. 27 Jan. 2009. <http://www.ncbi.nlm.nih.gov.ezproxy.lib.uconn.edu/pubmed
[3]
Bledsoe, Sanford C., Seth Koehler, Deborah L. Tucci, Jianxum Zhou, Colleen G. Le Prell, and Susan E.
Shore. "Ventral Cochlear Nucleus Responses to Contralateral Sound are Mediated by CNCommissural and Olivocochlear Pathways." JNeurophysiol (2009). Journal of Neurophysiology. 1
June 2009 <http://jn.physiology.org/cgi/content/abstract/91003.2008v1>.