Network activity patterns of corticofugal projection neurons in the auditory cortex

• Applicant: Professor Dr. Jan Jasper Hirtz
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 440234314

The auditory cortex (AC) is not only a high-order processing hub of auditory information, but also a modulator of upstream auditory pathways via the auditory corticofugal (ACF) system. Descending projections from the AC terminate in virtually all auditory brainstem nuclei, including the inferior colliculus (IC), and cochlear nucleus (CN). Despite the importance of the ACF system in hearing, surprisingly little is known about its physiology, which can be partly attributed to its complex structure. ACF neurons are located in deep AC layers, most of them projecting to only one auditory brainstem nucleus. However, due to complex connectivity patterns between the brainstem nuclei, direct and indirect effects of ACF projections have to be considered. Thus, past studies of the ACF system have been unable to attribute specific physiological roles to the different brainstem-targeting projection pathways. Two-photon in vivo microscopy now offers the opportunity to identify specific ACF neurons and image their activity. In the proposed project, we will express the genetically encoded Ca2+-sensor GCaMP7f for imaging of neuronal activity in the mouse AC via injection of adeno-associated virus (AAV). In addition, ACF neurons projecting either to the IC or CN will express a red fluorophore after injection of a retrogradely labeling AAV (AAV2-retro) into the given brainstem nucleus. This way, we can distinguish activity of ACF neurons from activity of surrounding (non-ACF) neurons and compare the properties of the two populations. Using pure tone acoustic stimulation, we will analyze the tonotopic organization of ACF neurons in relation to the overall tonotopy of the AC. Using complex acoustic stimulations, we aim to characterize the contribution of ACF neurons to functional AC networks. We hypothesize these activity patterns to differ between neurons projecting to the IC and those projecting to the CN, as these ACF projections probably fulfill different physiological functions in the auditory system. In addition, we expect to observe this functional separation at the level of direct synaptic cortical connectivity between ACF neurons as well. For this last part, AAV2-retro will be injected into both brainstem nuclei, one into the IC, labeling ACF neurons in green, and one into the CN, labeling ACF neurons in red. Dual patch-clamp recordings in acute cortical slices will be used to assess synaptic connectivity between, and within, the two groups. The data obtained will offer new insights into structure and function of the ACF system, contributing profoundly to the understanding of auditory information processing.

• DFG Programme: Research Grants