Banca de QUALIFICAÇÃO: THAWANN MALFATTI BORGES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : THAWANN MALFATTI BORGES
DATE: 27/01/2020
TIME: 10:00
LOCAL: INSTITUTO DO CÉREBRO
TITLE:

CaMKIIa+ dorsal cochlear nucleus neurons are necessary for tinnitus perception

KEY WORDS:

tinnitus, cochlear nucleus, neurons, mice

PAGES: 60
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUMMARY:

Noise-induced tinnitus is a phantom sound, perceived without a physical source, caused by over-exposure to loud noise. The dorsal cochlear nucleus (DCN), a region known to integrate somatosensory and auditory pathways, has been identified as a potential key structure in the generation of phantom sound perception. Here, we decrease activity of the Calmoduline Kinase II alpha (CaMKIIa) positive DCN neurons to investigate their role in tinnitus perception. Mice were over-exposed to loud noise (90dBSPL, 1h, followed by 2h of silence) to induce tinnitus. Auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) test were recorded two days before and two weeks after noise over-exposure to assure tinnitus induction (significant decrease in GPIAS response) without permanent hearing loss. Activity of CaMKIIa+ neurons in the DCN was decreased by expressing and activating Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs). Animals were retested on the following day in the GPIAS test but under effect of a systemic clozapine-n-oxide (CNO, 0.5mg/kg) administration. We found a decrease in tinnitus-like responses when CaMKIIa+ DCN neurons activity was decreased (p = 0.038, n = 11 mice), while the control group (control virus; CaMKIIa-YFP + CNO) showed no improvement in GPIAS responses (p = 0.105, n = 6). In another set of experiments, we administered CNO 30 minutes before the noise over-exposure to decrease activity of CaMKIIa+ DCN neurons (n = 6 experimental and 6 control mice), and data shows that lowering CaMKIIa+ neurons activity cannot prevent tinnitus induction. Our results suggests that CaMKIIa+ cells in the DCN may have a role in maintaining tinnitus perception in mice.

BANKING MEMBERS:
Interno - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Presidente - 1976236 - EMELIE KATARINA SVAHN LEAO
Interno - 1824636 - RICHARDSON NAVES LEAO
Interno - 2183828 - TARCISO ANDRE FERREIRA VELHO