Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice

• Autor(a) principal: Sousa, Ingrid Nogueira
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFRN
• Texto Completo: https://repositorio.ufrn.br/jspui/handle/123456789/27679
• topic: CNPQ::OUTROS::CIENCIAS; Zumbido; Córtex auditivo; Patch Clamp; Células piramidais e células martinotti

Tinnitus is an abnormal state of nerve cell activity of the auditory system, leading to perception of phantom sounds such as ringing of the ears. Although tinnitus perception is not harmful per se, it can lead to severe psychological stress, anxiety and depression. Several studies indicate the auditory cortex as a potential target for transcranial magnetic/direct current stimulation to alleviate tinnitus perception, yet little is known of how tinnitus alters cortical circuits. Here we investigate cellular populations of layer 5 (L5) of the primary auditory cortex (A1) in a mouse model of noise-induced tinnitus. L5 pyramidal cells (PCs) were routinely subdivided into putative corticofugal projecting type A, or contra-lateral projecting type B PCs, post hoc. We found that membrane properties were different between younger (P16-23) and mature cells (P38-52), and therefore we opted to only include animals ≥1 month of age for noise-overexposure (4-20kHz, 90dB, 1,5 hrs). Next we compared passive and active membrane properties between the two PC subtypes as well between control and tinnitus-like animals. We also used transgenic Chrna2-cre mice to investigate inhibitory Martinotti cells between the experimental groups. We found that noise overexposure did not change passive membrane properties of either type A or type B PCs when examined 5-8 days later. Instead we found type A PCs to fired with a significantly lower firing frequency in response to positive current injections (150pA) following noise overexposure (control A: 20,3±1,8Hz, n=11, noiseoverexposed: 16,1±1,2Hz, n=19, p=0.050), while contrarily type B PCs significantly increased steady state firing frequency (Control B: 13,3±1,3Hz, n=13, noise-overexposed: 19,5±2,4Hz, n=22, p=0,048). Interestingly, preliminary data from Martinotti cells from noise-overexposed animals show a trend of higher initial firing frequency than control (control M: 70,05±6,5Hz, n=8, noise-overexposed: 80,5±3,4Hz, n=12) and steady state frequency (control M: 20,35±4,4Hz, noise-overexposed: 33,5±4,9Hz). Since Martinotti cells are specifically connected to type A PCs through recurrent inhibition, this could suggest that Martinotti cells protects type A PCs from acoustic over-activity. Preliminary data using a genetic activity marker (CaMPARI, n=4 mice) also suggests that noise-overexposure does not affect cells uniformly in layer 5-6 of the A1.Together, these results are a first step in identifying specific cortical neurons affected by noise-induced tinnitus and quantify electrophysiological differences seen for each subtype. To understand the cellular mechanisms of tinnitus is crucial for improving treatments of tinnitus using cortical stimulation.