Signatures of Somatic Inhibition and Dendritic Excitation in Auditory Brainstem Field Potentials

Extracellular voltage recordings (V_e; field potentials) provide an accessible view of in vivo neural activity, but proper interpretation of field potentials is a long-standing challenge. Computational modeling can aid in identifying neural generators of field potentials. In the auditory brainstem of cats, spatial patterns of sound-evoked V_e can resemble, strikingly, V_e generated by current dipoles. Previously, we developed a biophysically-based model of a binaural brainstem nucleus, the medial superior olive (MSO), that accounts qualitatively for observed dipole-like V_e patterns in sustained responses to monaural tones with frequencies >~1000 Hz (Goldwyn et al., 2014). We have observed, however, that V_e patterns in cats of both sexes appear more monopole-like for lower-frequency tones. Here, we enhance our theory to accurately reproduce dipole and non-dipole features of V_e responses to monaural tones with frequencies ranging from 600 to 1800 Hz. By applying our model to data, we estimate time courses of paired input currents to MSO neurons. We interpret these inputs as dendrite-targeting excitation and soma-targeting inhibition (the latter contributes non-dipole-like features to V_e responses). Aspects of inferred inputs are consistent with synaptic inputs to MSO neurons including the tendencies of inhibitory inputs to attenuate in response to high-frequency tones and to precede excitatory inputs. Importantly, our updated theory can be tested experimentally by blocking synaptic inputs. MSO neurons perform a critical role in sound localization and binaural hearing. By solving an inverse problem to uncover synaptic inputs from V_e patterns we provide a new perspective on MSO physiology.

SIGNIFICANCE STATEMENT Extracellular voltages (field potentials) are a common measure of brain activity. Ideally, one could infer from these data the activity of neurons and synapses that generate field potentials, but this "inverse problem" is not easily solved. We study brainstem field potentials in the region of the medial superior olive (MSO); a critical center in the auditory pathway. These field potentials exhibit distinctive spatial and temporal patterns in response to pure tone sounds. We use mathematical modeling in combination with physiological and anatomical knowledge of MSO neurons to plausibly explain how dendrite-targeting excitation and soma-targeting inhibition generate these field potentials. Inferring putative synaptic currents from field potentials advances our ability to study neural processing of sound in the MSO.