Back Past events: Miguel Merchan. Peripheral and central hearing loss at long term: Bottom up and top down neuroplasticity

Miguel Merchan. Peripheral and central hearing loss at long term: Bottom up and top down neuroplasticity

- BCBL Auditorium
What: Peripheral and central hearing loss at long term: Bottom up and top down neuroplasticity.
Where: BCBL auditorium
Who: Miguel Merchan, PhD, Full Professor, Dpto. de Biología Celular y Patología, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain.

When: 12 noon

To try to better understanding the role of the auditory descending pathway in nervous system reorganization after deafness, three different animal models will be analyzed in this lecture.

Model 1 (Ossicular chain removal) – Conductive hearing loss

Model 2 (Auditory cortex aspiration) – Central Hearing loss

Model 3 (Cochlear puncture) – Sensorineural peripheral hearing loss.

Model 1 and 2

The descending corticofugal pathway regulates the response to sound of the inner ear through its direct connections to the brainstem olivocochlear (OC) efferent system. In order to compare plastic changes in the inner ear induced by sound or by central nervous system descending regulation, we compare an animal model of unilateral conductive deafness (model 1 – ossicular middle ear chain removal) with another of central deafness (model 2 – auditory cortex – AC- restricted ablation). To do this, we analyze at long term (1, 7 and 15 days post lesion time) by WB and qPCR, changes in both animal models the expression of genes or proteins of specific molecules involved in IHC neurotransmission and OHC micromechanic.

Both changes in model 1 or in model 2, triggers a long-term adaptive reorganization in the inner ear molecular machinery. In model 2, a group of specific genes involved in efferent regulation of IHC (glutamate dehydrogenase, subunits of AMPAr – GluR2, GluR3, GluR4, Ach – α 7, Dopamine D2, α1 and γ2) show significant changes both after comparing with controls or the ipsilateral with the contralateral ear, at all postlesion time groups. One of the most significant finding (1 day after lesión) was the upregulation of α7 Ach and α1 GABA A receptors genes, with changes up to 40 fold. These high FC values partially recovers at 15 days pl. We discuss this new data in relationship with previous results of our laboratory on changes in the electromotile protein Prestin, and βactin and α9-10 Ach receptors (Lamas et. Al 2015). Model 3 Bilateral lesions were performed in Wistar rats by middle ear ossicular removal and surgical puncture of the cochlea. Auditory Brainstem Responses did not show sound evoked activity in both lesioned animal groups. Brains were sectioned serially in the coronal plane and immunostained for GluR2/3 AMPA receptors and for ARC/Arg3.1. To analyze changes in immunoreactivity, high resolution pictures of 5 equivalent representative rostro-caudal sections (IA: 2.70, 3.20, 3.40, 4.20, 4.70 – Paxinos and Watson coordinates) containing auditory, visual and somatosensory cortices (AC, VC y SSC) per case were taken using a motorized stage.

Cytoarchitectural density maps were made after gray level normalization of all sections. Rat brain cortex subdivisions were defined by matching guidelines in previous publications with our own results. 15 days after lesion, we observed an intense loss of immunoreaction density in all layers of the AC. There was also evidence of changes in density, cytoarchitecture and layering in VC and SSC. In GluR2/3 immunostained sections, we found loss of staining in layers II and III of the AC in contrast with an increase in density of immunoreaction in the VC and SSC.Peripheral deafness induces at long term partially reversible drop of AMPA receptor synthesis and trafficking in the AC and also a crossmodal reorganization in the VC and SSC.

In conclusion we provide some evidence to discuss if hearing loss causes a long term brain reorganization which is under control of the descending pathways.