The role of dendritic inputs in high-fidelity temporal processing of phase-coding neurons in the mammalian anteroventral cochlear nucleus

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Spherical bushy cells (SBC) of the anteroventral cochlear nucleus code the temporal structure of the auditory stimulus with microsecond precision. For this the auditory brainstem circuitry shows a remarkable degree of task-specific specialization, especially regarding the biophysical, cellular and synaptic hardware for ultrafast and precise processing of auditory information. Auditory brainstem systems evolved however to optimally function over a wide range of stimulus conditions, which demands rapid adaptability of the neuronal function. For this, inhibitory and modulatory inputs that also terminate in the AVCN are potential candidates. In the last funding period of DFG priority program 1608 we identified acetylcholine as a modulator of the excitability of time-coding neurons in the AVCN. Application of acetylcholine to SBC transiently (milliseconds to seconds) and also tonically (several minutes) depolarizes the resting membrane potential. It thus acts on two different time scales. We could already show that the rapid depolarization is mediated by ionotropic alpha-7 AChR.In the second funding phase of this project we now want to elaborate on the cellular mechanisms by which acetylcholine acts in the AVCN. Initially we want to focus on postsynaptic effectors of the tonic modulatory response. Next, we want to systematically analyze whether indications of a modulatory effect on the presynaptic release probability of the endbulb of Held synapse can be confirmed. Finally, we want to study the effect the combined cholinergic influence has on the temporal acuity of the SBC output spiking.These experiments will be performed in acute slice preparations of the gerbil auditory brainstem. A combination of whole-cell recordings of membrane potentials/currents, local pressure application of pharmacological agents and electrical stimulation of axonal connections will be used to address our questions. In addition to the in-vitro experiments we want to apply a data-constrained computer model of the spherical bushy cells, which was created in funding phase 1. This will allow us to systematically study the effect of modulatory inputs and dendritic excitation under a wide variety of simulated sound-stimulus paradigms.It is the objective of the experiments proposed in this grant application to study a mechanism that imparts stimulus-specific adaptability to the ultra-fast and precise auditory brainstem circuitry of the auditory system.