Subclassification of neocortical neurons by electrophysiological membrane properties - Impact of noise overexposure

Abstract

Loud noise-exposure can generate noise-induced tinnitus in both humans and animals. Several studies have observed that the noise-exposure (NE) can alter neuronal activity of many, if not all auditory nuclei, including the primary auditory cortex (A1). Despite the A1 providing important descending feedback to nuclei of the auditory pathway, still little is understood of how NE affects electrophysiological membrane properties of specific types of neurons in the A1. Here, we record firing properties from pyramidal cells (PCs) and Martinotti cells (MCs) of layer 5, the main cortical output layer, of the A1 in control conditions or one week after a noise overexposure (4-18 kHz, 90dBs, 1.5 h, followed by 1.5 h silence). MCs of the A1 were furthermore compared to control MC recordings from the primary motor cortex (M1) to elucidate speculations of morpho-electrical subtypes of L5 MCs. Electrophysiological subtypes of pyramidal cells and MCs were identified using principal component analysis and clustering, in combination with genetic markers for the MCs. We found that NE changes firing frequency of L5 PCs in opposite directions after depolarization current injections, where Type A PCs had a decrease in initial (p = 0.02) and steady state firing frequency (p = 0.050) and Type B PCs showed a significant increase in in steady state firing frequency (p = 0.048). Additionally, L5 MCs in A1 showed a significant increase in initial (p = 8.5 × 10−5) and steady state firing frequency (p = 6.3 × 10−5) after noise overexposure. When comparing control groups of MCs in L5 of A1 and M1 we observed, through PCA analysis, the formation of two clusters based on 14 membrane properties assessed. We called the groups, Type 1 and Type 2 MCs and they significantly differed in 10 parameters for A1 and 11 parameters for M1, showing that L5 MCs in the cortex are not a homogeneous group and can be subdivided into two main clusters. In conclusion, loud NE was seen to cause distinct effects in Type A and Type B L5 PCs and inhibitory L5 MCs, which appears to alter activity of descending and contralateral feedback in the auditory system. Lastly, we examined if differences in electrophysiological properties of subtypes of MCs are detectable after noise overexposure and found the data again to separate into two clusters. Together this thesis shows that L5 MCs from different cortical areas displayed strikingly similar characteristics, and that subclassification of MCs may be important for better understanding effects of loud noise exposure on cortical networks of the primary auditory cortex in order to develop treatment options to restore normal level of activity within the A1.