Banca de DEFESA: BARBARA CIRALLI BOERNER

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : BARBARA CIRALLI BOERNER
DATE: 23/11/2022
TIME: 14:00
LOCAL: meet.google.com/hcf-mkqo-brm
TITLE:

Quantification of auditory sensory gating in mice models of tinnitus and psychiatric disorders

KEY WORDS:

Sensory gating, tinnitus, SLC10A4, Hippocampus, Auditory Event Related Potentials

PAGES: 100
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

This thesis investigates auditory sensory gating, a neural mechanism of filtering repetitive and irrelevant sounds from the environment, which is important to prevent information overload at higher cortical areas. Disturbances in sensory gating are associated with several psychiatric disorders, such as schizophrenia and attention-deficit/hyperactivity disorder, while its role in auditory phantom perception is less studied. In the first chapter, sensory gating alterations in an animal model of tinnitus are described. The objective of this study was to first investigate whether noise-exposure interferes with auditory gating, and second, if nicotine or natural extracts of cannabis would improve or impair auditory pre-attentional processing in noise-exposed mice. Anesthetized C57BL/6J mice were exposed to a 9-11 kHz narrow band noise (90 dBSPL for 1 hr), hearing thresholds were measured and tinnitus was assessed using Gap prepulse inhibition of acoustic startle (GPIAS). Mice were next implanted with electrode arrays to assess auditory event-related potentials (aERPs) in the dorsal hippocampus in response to paired sound clicks. Alterations of aERPs under nicotine (1.0 mg/kg, intraperitoneal (i.p.) or THC-rich cannabis extract (100 mg/Kg, i.p.) were evaluated (in isolation or in combination). Our results show that mice with behavioral evidence of tinnitus display auditory gating of repetitive click, but with larger amplitudes and longer latencies of the aERP negative peak (N40) component compared to sham exposed animals. In contrast, no difference was observed in the positive peak (P80) amplitude and latency between groups or treatments. The combination of cannabis extract and nicotine improved auditory gating ratio in mice with noise-induced tinnitus by strongly increasing the first N40 click amplitude but without altering the second click response amplitude. Furthermore, the increased latency of the N40 component suggests altered temporal processing of triggered attention in mice with tinnitus due to an increased sensitivity to the exposure to cannabis extract. In summary, nicotine and cannabis extract treatments were shown to alter sensory gating in mice with behavioral evidence of tinnitus, indicating that the altered central plasticity in tinnitus is more sensitive to the combined actions on the cholinergic and the endocannabinoid systems. In the second chapter, knock-out mice for an orphan solute carrier gene, slc10a4 were screened for alterations in sensory gating. The SLC10a4 -/- mice, which lack a monoaminergic and cholinergic associated vesicular transporter protein and show accumulation of dopamine in the striatum synaptic clefts, were specifically investigated for the identification of a potential animal model for psychiatric disorders. Auditory ERPs in response to paired sound clicks were recorded by intrahippocampal single shank multichannel electrodes and amplitude and latency of click responses were measured. Wildtype (WT) littermates and Slc10a4-/- mice also received subanesthetic doses of ketamine (5 mg/kg and 20 mg/kg) to provoke psychomimetic behavior. WT animals showed N40 second click (S2) response amplitude significantly decreased compared to the first click (S1) response under saline and ketamine 5 mg/kg treatments, but not upon ketamine (20 mg/kg) verifying the classic psychomimetic effect of ketamine. Slc10a4-/- mice instead showed no significant differences between N40 S1 and S2 response amplitudes at any ketamine dose. Auditory gating (S2/S1 ratio) was similar between WT and Slc10a4-/- mice, however, the negative component (N40) of the aERP showed increased latency while the positive component (P80) showed higher amplitude in Slc10a4-/- mice compared to WT littermates. This study  indicates that both the cholinergic and monoaminergic systems participate in the temporal coding (response latency) of the aERP N40 component, and in the amplitude of the aERP P80 component. The results of this thesis adds knowledge to the identification of electrophysiological signatures for identifying abnormal neuronal networks, which is important for future establishment of clinically relevant biomarkers of brain disorders. Moreover, the Slc10a4-/- mice were concluded to not be a suitable model for schizophrenia but might serve as a model for other neuropsychiatric conditions such as attention deficit/hyperactivity disorder.

COMMITTEE MEMBERS:
Interno - 1728817 - CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
Externo à Instituição - CLEITON LOPES AGUIAR - UFMG
Presidente - 1976236 - EMELIE KATARINA SVAHN LEAO
Interna - 1871878 - KERSTIN ERIKA SCHMIDT
Externo à Instituição - MARINE RAQUEL DINIZ DA ROSA - UFPB