UC Santa Cruz

AbstractNeuron Activation in Response to Auditory Stimulation Gabriela Llarena Gaining genetic access to neurons allows us to study the structure and function of the mammalian auditory system. Audition captures sound stimuli detected from the environment and sends this information to the brain through the auditory pathway. The information gathered by the auditory system is integrated with information gathered from the other sensory modalities: vision, olfaction, touch, and gustation; this allows us to modify our behavior accordingly and is crucial for survival. Methods to identify neuron populations based on their response properties are limited, as most genetic manipulation experiments identify neurons based on their anatomy or genetic composition. Neuroscientists have developed a novel tool that genetically targets different neuron populations based on their functional criteria. The fos/TRAP2 method, or “Targeted Recombination of Active Populations” (TRAP), genetically targets populations of auditory-responsive neurons when exposed to an auditory stimulus (Guenthner, Casey J, et al., 2013). Using a transgenic mouse line of Fos2A-iCreERT2, or TRAP2, knock-in mice, I designed an auditory stimulation experiment that utilizes a cre-inducible system in cells that express fos in the presence of 4-Hydroxytamoxifen to identify and locate the auditory-responsive neuron populations. I found that mice exposed to an auditory stimulus expressed greater numbers of active cells in areas receiving auditory inputs, such as the primary auditory cortex (A1), superior colliculus (SC), and inferior colliculus (IC), than in mice that had their ears plugged; in the primary somatosensory cortex (S1), both experimental conditions showed similar numbers of active neurons. These results demonstrate how the fos/TRAP2 method could serve as a tool to label neurons that respond to auditory stimuli; this method uses the effector gene R26tdTomato to fluorescently label cells, which can be analyzed using immunohistochemistry. The fos/TRAP2 method and analyses can provide insight into different auditory-responsive neuron populations; it can be used to determine which neuronal markers the cells express to identify their type, such as whether they are excitatory or inhibitory neurons, and the cells’ defining characteristics. Additionally, this method can be used to sort cells for RNA sequencing (RNA Seq) analysis or to induce expression of optogenetic tools used to assay auditory circuitry. Identifying the function of different auditory-responsive neuron populations can be used to further investigate the auditory pathway and sensory integration to better understand how mammals detect and process sound.