Banca de DEFESA: THAWANN MALFATTI BORGES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : THAWANN MALFATTI BORGES
DATE: 27/03/2020
TIME: 14:00
LOCAL: INSTITUTO DO CEREBRO
TITLE:

The role of activity of the dorsal cochlear nucleus in tinnitus perception in mice

KEY WORDS:

tinnitus, cochlear nucleus, neurons, mice

PAGES: 127
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 first target the output layer of the DCN using viral vectors containing the CaMKIIa (CaMKIIa) promoter to express optogenetic proteins and investigate how exciting (Channelrhodopsin-2, ChR2) or inhibiting (enhanced Archaerhodopsin 3.0, eArch3.0) those DCN cells affects the DCN circuitry response to sound. We found that optogenetic stimulation of DCN cells expressing CaMKIIa-ChR2 or CaMKIIa-Arch can distort DCN units responses to sound. Next, we chemogenetically decrease activity of the same subgroup of DCN neurons using the Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs) to investigate their role in tinnitus perception. Mice were 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 exposure to confirm tinnitus perception (significant decrease in GPIAS response) without permanent hearing loss. Activity of CaMKIIa-hM4Di+ neurons in the DCN was decreased by expressing and pharmacologically activating the hM4Di DREADDs. Perception of tinnitus was evaluated when inhibitory hM4Di DREADDs were activated by systemic clozapine-n-oxide (CNO, 0.5mg/kg) administration. We found CNO to decrease tinnitus-like responses (p = 0.038, n = 11 mice), compared to the control group that showed no improvement in GPIAS responses (control virus; CaMKIIa-YFP + CNO, p = 0.696, n = 7 mice). Unit recordings confirmed CNO to decrease DCN firing frequency, alter best frequency and broadness of response to sound. Next CaMKIIa-hM4Di-mCherry positive DCN neurons were instead chemogenetically inhibited during the noise exposure (n = 6 experimental and 6 control mice), but this did not prevent tinnitus induction, nor did CNO administration 2 weeks later improve gap-detection indicating tinnitus perception was not decreased. Our results suggest that CaMKIIa-hM4Di-mCherry positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.

BANKING MEMBERS:
Presidente - 1976236 - EMELIE KATARINA SVAHN LEAO
Externo à Instituição - MARINE RAQUEL DINIZ DA ROSA - UFPB
Externo à Instituição - NIVALDO ANTONIO PORTELA DE VASCONCELOS - UFPE
Interno - 1824636 - RICHARDSON NAVES LEAO
Interno - 1698305 - RODRIGO NEVES ROMCY PEREIRA
Interno - 1842426 - SERGIO TULIO NEUENSCHWANDER MACIEL