Auditory learning in the mongolian gerbil (Meriones unguiculatus) investigated with auditory functional magnetic resonance imaging

Abstract

Learning auditory cues and distinguishing between them is imperative for our daily social interactions and essential for our perception of the external world. Disorders in the hearing system and in auditory learning can lead to social isolation and create a wide variety of health risks. Auditory research aims to understand mechanisms of auditory learning, e.g. learning- induced brain plasticity changes to enable treatment of such disorders. In humans, the extent of this research is limited in its invasiveness due to ethical restrictions. Mongolian gerbils (Meriones unguiculatus) are rodents with hearing thresholds similar to humans. Their ability to perform complex auditory tasks makes gerbils a popular animal model for invasive auditory learning experiments that cannot be performed on human participants. Auditory functional magnetic resonance imaging (fMRI) would be a suitable non-invasive method to improve translatability from auditory research implemented in gerbils to ongoing human research. But so far this method has not been implemented in gerbils. To facilitate direct comparison of gerbil and human auditory research, I established auditory fMRI in Mongolian gerbils. While doing so, an appropriate anaesthesia protocol was found, fMRI sequences optimized for the rodent model, and an auditory stimulation setup, intended for human auditory fMRI, refined for usage in small animals. With optimization of the auditory fMRI measurement setup, acquired auditory activation patterns feature bilateral activation in auditory cortex, auditory thalamus and auditory midbrain. In a second project, the newly established auditory fMRI was evaluated with cerebral blood flow SPECT imaging. More precisely, the effects of medetomidine anaesthesia and the substantial fMRI background noise on auditory activation patterns were investigated. In this study, only minor effects of medetomidine anaesthesia were found. The fMRI background noise showed more impact on the obtained auditory activation patterns, in the form of lowered subcortical activation to auditory stimulation and increased activation in higher order auditory cortex areas. Finally, auditory fMRI was utilized to investigate auditory learning in Mongolian gerbils in a standard tone discrimination task in a shuttle box. The task was implemented in two alternative designs, one adding punishment for “False Alarms” to the aversive avoidance paradigm. With repeated application of auditory fMRI, we were able to distinguish activation changes and consolidation processes in various brain structures with a clear and significant performance dependency. The addition of punishment in the training led to higher correlation of the animals’ learning score to the activation levels of multiple neuromodulatory and associative brain regions. These observed activation changes attest to the usefulness of auditory fMRI in Mongolian gerbils for auditory research and its potential in bridging the gap to human research.