Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-26T20:08:35Z No. of bitstreams: 1 ThawannMalfattiBorges_DISSERT.pdf: 27333324 bytes, checksum: 7928d876effa4fd0184f0b246ecd1c34 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-29T20:35:41Z (GMT) No. of bitstreams: 1 ThawannMalfattiBorges_DISSERT.pdf: 27333324 bytes, checksum: 7928d876effa4fd0184f0b246ecd1c34 (MD5) / Made available in DSpace on 2016-04-29T20:35:41Z (GMT). No. of bitstreams: 1 ThawannMalfattiBorges_DISSERT.pdf: 27333324 bytes, checksum: 7928d876effa4fd0184f0b246ecd1c34 (MD5) Previous issue date: 2015-06-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Tinnitus is the perception of a sound in the absence of a corresponding physical stimulus. It is not clear yet what mechanisms are involved in tinnitus and how it starts and/or becomes chronic. Due to the relationship between tinnitus and somatosensory trauma/stimuli, 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 target specific neuronal populations in the DCN to allow further investigation on how this region may contribute to the generation of tinnitus signals that spread to other auditory areas. We examined the expression of optogenetic proteins (Channelrhodopsin 2 - ChR2; and enhanced Archaerhodopsin 3.0 - eArch3.0), targeting neurons expressing Calmoduline Kinase II alpha (CaMKIIa) promoter in wild-type C57/Bl6 mice and neurons expressing nicotinic acetylcholine receptor subunit alpha-2 promoter (ChRNA2) in ChRNA2- Cre transgenic C57/Bl6 mice, using local virus injection, verified by fluorescence microscopy. Unit responses were differentiated based on their electrophysiological response to sound. We then investigated if firing of neurons expressing optogenetic tools can be controlled in vivo and if the same neurons also fire action potentials in response to precisely timed sound stimulation. Both in vivo and preliminary in vitro data shows that neurons expressing ChR2 do respond to sound, and that they furthermore also can respond to light stimulation with a stable and similar waveform. Moreover, in vivo data shows that neurons expressing eArch3.0, responding to sound, will decrease their firing rate when exposed to green light. Thereby showing that optogenetic tools can be used functionally in the DCN, it is possible to further test tinnitus theories by, for example, producing an increased firing rate in the DCN, trying to mimic tinnitus; or inhibiting increased spontaneous firing rate in the DCN of animals with noise-induced or salycilate-induced tinnitus.

GABAB receptors play an important role in regulation of neuronal excitability and stability of neural microcircuits. It is well known that dysregulation of slow GABAergic signalisation can lead to many pathological conditions (epilepsy, anxiety etc.). Current research indicates that the imbalance in the inhibitory transfer, caused by changes in the expression of GABABR in the auditory system could play an important role in the progression of tinnitus. The goal of the present thesis was to determine the distribution of the GABAB receptor and its auxiliary subunit KCTD12 in the mouse auditory cortex and the dorsal cochlear nucleus (DCN). Furthermore, a change in GABAB receptor localization in the DCN was observed in mice exposed to an acoustic stress. The GABAB receptor was expressed across the entire auditory cortex, both on the body and on the neuronal fibres. On the contrary, KCTD12 was found only in a particular subgroup of neurons that includes VIP (vasoactive intestinal peptide) and cholecystokinin positive interneurons., GABABR and KCTD12 protein were found in all layers and in all studied cells types (fusiform, cartwheel and stellate) of the DCN. Acoustic trauma of the WT mice resulted in GABAB receptor internalization specifically in fusiform cells that are the main projection neurons of the...

Le vieillissement dit "naturel", affecte physiologiquement les structures auditives périphériques; il en va de même du collicule supérieur (CS) lors du traitement des signaux auditifs et visuels. Chez le rat âgé, la sensibilité auditive périphérique diminue et l’extraction des attributs des signaux auditifs est modifiée, et ce, dès les noyaux cochléaires (premiers relais centraux de la voie auditive ascendante). De plus, les propriétés spectrales, temporelles et directionnelles des neurones auditifs du CS sont altérées lors du vieillissement. Ceci se manifeste aussi au niveau de l’organisation topographique de la sensibilité à la direction qui est abolie au sein des couches profondes du CS. Dans la même optique, l’extraction des attributs des fréquences spatiales concentriques mobiles (en présence ou en absence d’objet sonore modulé en amplitude) est altérée aussi au niveau des neurones audiovisuels du CS lors du vieillissement. En effet, au niveau spatial, chez l’animal âgé, la présence de déficits visuels est particulièrement marquée par une diminution de la sensibilité aux stimuli visuels et audiovisuels mobiles et rapides lors du déplacement de l’organisme dans son environnement. Compte tenu de l’ampleur des changements qui s’installent avec le vieillissement au niveau des structures périphériques et centrales, inévitablement, les mécanismes nerveux de la plasticité audiovisuelle de bas niveau, i.e. au niveau des neurones du CS, sont perturbés. En outre, chez l’animal âgé, le gain audiovisuel induit par l’activité des neurones du CS ne produit pas d’amélioration notable par rapport à la modalité unisensorielle. Dans l’ensemble, ces résultats montrent que le vieillissement perturbe l’activité neuronale du CS permettant de détecter les informations sensorielles pertinentes dans un environnement audiovisuel complexe. / Age-related physiological changes affect the peripheral auditory structures; this also applies to the superior colliculus (SC) auditory and visual processes. In aged rats, the peripheral hearing sensitivity decreases and at more central regions, particularly the first central node, in the ascending auditory projections, auditory processing of sounds is altered. Furthermore, at the level of the SC, spectral, temporal and directional properties of auditory neurons are also altered during aging. In addition, no systematic directional spatial arrangement is encountered among the neurons of aged rats, implying that the topographical organization of the auditory directional map is abolished in the deep layers of the SC. Moreover, in a condition where SC visual neurons are stimulated with looming concentric sinusoidal gratings (in the presence or in the absence of modulated audio signals), visual deficits in aged animals are particularly marked by a decrease in sensitivity to fast moving visual and audiovisual stimuli during self-motion. Given the links of age-related changes in the peripheral and in the central structures, inevitably, the mechanisms underlying the neuronal audiovisual plasticity, in the low-level (SC), are somehow disrupted. Specifically, in aged animals, the presence of the auditory stimulus when coupled with the visual signal did not enhance the response activity of the visual neurons. This seems to suggest that the mechanism that may serve to amplify the visual signal under weak or ambiguous and noisy conditions thus improving greater behavioral relevance of detecting rapidly approaching visual and audiovisual moving objects during self-motion is altered with aging. Overall, these results show that aging disrupts the SC neuronal activity that enables detection of relevant sensory information in a complex audiovisual environment.