Midway Evaluation - Sudeep Mukerji

The candidate is affiliated to the Department of Clinical Medicine. Principle supervisor - Nils Erik Gilhus.

Abstract

Sudeep Mukerji

The middle ear muscle (MEM) reflex and the olivocochlear (OC) reflex are two major descending systems to the auditory periphery. Both pathways begin with sound presented to the ear. Transduction of sound occurs in the cochlea in the inner ear, resulting in an action potential that is transmitted along the auditory nerve to the cochlear nucleus in the brainstem (the first relay station for all ascending sound information originating in the ear). Unknown interneurons in the ventral cochlear nucleus project either directly or indirectly to MEM motoneurons located elsewhere in the brainstem. These motoneurons provide efferent innervation to the MEMs; the stapedius and the tensor tympani. The two middle ear muscles (MEMs) contract in response to both acoustic and non acoustic stimuli to increase middle ear impedance and attenuate the intensity of sound energy reaching the inner ear (cochlea). Similarly the Olivocochlear (OC) neurons (medial and lateral) respond to sound and provide descending input that controls processing in the cochlea allowing for the optimal localization of sound.

Although the ascending and descending limbs of these reflex pathways have been well characterized, the identity of the reflex interneurons within these two systems is not known, as are the source of modulatory inputs to these pathways. The aim of this thesis is to use modern labeling techniques in the form of chemical (Fluorogold) and viral (Pseudo-rabies) tracers to conduct a morphometric analysis of the labeled neuronal components within these two systems. For example, the identities of the neurons in the pathways providing inputs to OC neurons are incompletely understood. To explore these pathways, the pseudorabies virus acted as a retrograde transneuronal tracer to label OC neurons and their inputs in guinea pigs. Labeling of OC neurons began 1 day after injection into the cochlea. On day 2 (and for longer survival times), transneuronal labeling spread to the cochlear nucleus, inferior colliculus, and other brainstem areas. There was a correlation between the numbers of these transneuronally labeled neurons and the number of labeled medial (M) OC neurons, suggesting that the spread of labeling proceeds mainly via synapses on MOC neurons. Transneuronal labeling was also observed in the auditory cortex.

The study also investigated the number and morphology of tensor tympani motoneurons (TTMNs) in mice using Fluorogold, a retrograde neuronal tracer. After injections of Fluorogold into the tensor tympani muscle, a column of labeled TTMNs was identified ventro-lateral to the ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to their morphological characteristics into three subtypes: "octopus-like", "fusiform" and "stellate", suggesting underlying differences in function. Their dendrites were also studied to identify potential sources for non-auditory inputs. In order to add to a historical perspective to the findings, the following study focuses on aspects of work the literature concerning the contributions to auditory research of Hieronymous Fabricius (1533-1619) achieved by analyzing the translated Latin text that focuses on the middle ear muscles from a first edition of Fabricius' book entitled 'De Visione, Voce et Auditu' (The Vision, Voice and Hearing, 1600).

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